Retzius‐sparing versus standard robotic‐assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

Joel E Rosenberg; Jae Hung Jung; Zach Edgerton; Hunju Lee; Solam Lee; Caitlin J Bakker; Philipp Dahm

doi:10.1002/14651858.CD013641.pub2

Retzius‐sparing versus standard robotic‐assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

Authors' declarations of interest

Version published: 18 August 2020 Version history

https://doi.org/10.1002/14651858.CD013641.pub2

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Abstract

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Background

Robotic‐assisted laparoscopic prostatectomy (RALP) is widely used to surgically treat clinically localized prostate cancer. It is typically performed using an approach (standard RALP) that mimics open retropubic prostatectomy by dissecting the so‐called space of Retzius anterior to the bladder. An alternative, Retzius‐sparing (or posterior approach) RALP (RS‐RALP) has been described, which is reported to have better continence outcomes but may be associated with a higher risk of incomplete resection and positive surgical margins (PSM).

Objectives

To assess the effects of RS‐RALP compared to standard RALP for the treatment of clinically localized prostate cancer.

Search methods

We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings, up to June 2020. We applied no restrictions on publication language or status.

Selection criteria

We included trials where participants were randomized to RS‐RALP or standard RALP for clinically localized prostate cancer.

Data collection and analysis

Two review authors independently classified and abstracted data from the included studies. Primary outcomes were: urinary continence recovery within one week after catheter removal, at three months after surgery, and serious adverse events. Secondary outcomes were: urinary continence recovery six and 12 months after surgery, potency recovery 12 months after surgery, positive surgical margins (PSM), biochemical recurrence‐free survival (BCRFS), and urinary and sexual function quality of life. We performed statistical analyses using a random‐effects model. We rated the certainty of evidence using the GRADE approach.

Main results

Our search identified six records of five unique randomized controlled trials, of which two were published studies, one was in press, and two were abstract proceedings. There were 571 randomized participants, of whom 502 completed the trials. Mean age of participants was 64.6 years and mean prostate‐specific antigen was 6.9 ng/mL. About 54.2% of participants had cT1c disease, 38.6% had cT2a‐b disease, and 7.1 % had cT2c disease.

Primary outcomes

RS‐RALP probably improves continence within one week after catheter removal (risk ratio (RR) 1.74, 95% confidence interval (CI) 1.41 to 2.14; I² = 0%; studies = 4; participants = 410; moderate‐certainty evidence). Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 248 more men per 1000 (137 more to 382 more) reporting continence recovery.

RS‐RALP may increase continence at three months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06 to 1.68; I² = 86%; studies = 5; participants = 526; low‐certainty evidence). Assuming 750 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 224 more men per 1000 (41 more to 462 more) reporting continence recovery.

We are very uncertain about the effects of RS‐RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47 to 4.17; studies = 2; participants = 230; very low‐certainty evidence).

Secondary outcomes

There is probably little to no difference in continence recovery at 12 months after surgery (RR 1.01, 95% CI 0.97 to 1.04; I² = 0%; studies = 2; participants = 222; moderate‐certainty evidence). Assuming 982 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 10 more men per 1000 (29 fewer to 39 more) reporting continence recovery.

We are very uncertain about the effect of RS‐RALP on potency recovery 12 months after surgery (RR 0.98, 95% CI 0.54 to 1.80; studies = 1; participants = 55; very low‐certainty evidence).

RS‐RALP may increase PSMs (RR 1.95, 95% CI 1.19 to 3.20; I² = 0%; studies = 3; participants = 308; low‐certainty evidence) indicating a higher risk for prostate cancer recurrence. Assuming 129 per 1000 men undergoing standard RALP have positive margins, this corresponds to 123 more men per 1000 (25 more to 284 more) with PSMs.

We are very uncertain about the effect of RS‐RALP on BCRFS compared to standard RALP (hazard ratio (HR) 0.45, 95% CI 0.13 to 1.60; I² = 32%; studies = 2; participants = 218; very low‐certainty evidence).

Authors' conclusions

Findings of this review indicate that RS‐RALP may result in better continence outcomes than standard RALP up to six months after surgery. Continence outcomes at 12 months may be similar. Downsides of RS‐RALP may be higher positive margin rates. We are very uncertain about the effect on BCRFS and potency outcomes. Longer‐term oncologic and functional outcomes are lacking, and no preplanned subgroup analyses could be performed to explore the observed heterogeneity. Surgeons should discuss these trade‐offs and the limitations of the evidence with their patients when considering this approach.

PICOs

Population

Intervention

Comparison

Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

available in

Should we perform Retzius‐sparing RALP or standard RALP for clinically localized prostate cancer?

Review question

In men with prostate cancer who are having their prostate removed using surgery assisted by a robotic device (called robotic‐assisted laparoscopic prostatectomy or RALP), how does an approach that leaves the tissue connections between the front of the bladder to the back of the abdominal wall intact (so‐called Retzius‐sparing RALP) compare to surgery where these connections are cut (standard RALP).

Background

Urologists often use a robot to remove the prostate in men with prostate cancer. After surgery, men have a catheter that drains urine from their bladder. When this is removed, most men leak urine for some time. This problem is called incontinence and usually gets better within six to 12 months in most men. However, it can be very bothersome during this time.

Study characteristics

We included five studies in which chance determined whether men had Retzius‐sparing RALP or standard RALP. These studies included 571 men with an average age of about 65 years. The average prostate‐specific antigen level (PSA; higher levels of which may indicate that the man has prostate cancer) was 6.9 ng/mL and a little over half (54.2%) had prostate cancer that was found based on the PSA level but could not felt on rectal exam. In 233/331 (70.4%) men, they tried to spare the nerves that are responsible for erections.

Key results

We found that the Retzius‐sparing RALP probably improves continence within one week after the catheter comes out. It may also improve continence three months after surgery. We are very uncertain how serious unwanted effects compare between the two ways of doing the surgery.

Continence after Retzius‐sparing RALP may also be better after six months. At 12 months, continence is probably similar.

Men who have Retzius‐sparing RALP may be more likely to have positive surgical margins, meaning they still have cancer cells right at the cut edge of the prostate when viewed under the microscope. This may make it more likely that the cancer will come back. We are very uncertain about the effect of Retzius‐sparing RALP on PSA level that goes up within 12 months of surgery, which signals that there is cancer left behind. Urinary quality of life at three months may be similar with both types of surgery. We are very uncertain how Retzius‐sparing RALP affects the ability to achieve an erection.

Quality of the evidence

The quality of evidence ranged from moderate to very low depending on the outcome, meaning that we have moderate to very low confidence in the results.

Authors' conclusions

Implications for practice

Based on the current best evidence summarized in this review, Retzius‐sparing robotic‐assisted laparoscopic prostatectomy (RS‐RALP) compared to standard robotic‐assisted laparoscopic prostatectomy (RALP) may improve early continence up to six months and improve early urinary quality of life but ultimately results in similar continence outcomes at 12 months. The benefits of the Retzius‐sparing approach appear to be considerable but transient in nature. Trade‐offs of this approach are uncertainty around major adverse events, potency outcomes, sexual quality of life as well as biochemical recurrence‐free survival. Low‐certainty evidence suggests that positive surgical margin (PSM) rates are higher with this approach. Given that the purpose of radical surgery is surgical cure and long‐term disease‐specific survival, these findings should provide a cautionary note to men who are offered this approach. RS‐RALP is also widely regarded as technically more challenging that standard RALP, and should, therefore, potentially be reserved to more skilled and experienced urologic surgeons who have mastered the learning curve of standard RALP.

Implications for research

A number of important research implications can be drawn from this review.

As a modified approach of an operation performed for the purposes of surgical cure and extended cancer‐free survival, follow‐up of existing studies appears insufficient to determine its oncologic effectiveness. We hope that all included, as well as future, studies will report long‐term follow‐up for the review update.
It remains unclear whether the increase of PSM is inherent to the RS approach or an aspect that future refinement of surgical technique. will address. The IDEAL (Idea, Development, Evaluation, Assessment, Long‐term) framework has recognized that novel surgical approaches go through steps of development (D) and evaluation (E) that refer to improvement of the technique and individual surgeons' and practice's learning before they arrive at their form (Dahm 2014). It is possible that future modifications of RS‐RALP can avoid this issue.
All surgical trials preclude the possibility of blinding the surgeon, but an expertise‐based randomized controlled trial design appears feasible, thereby limiting the risk of performance bias (Cook 2015; Devereaux 2005). In such a trial, participants would not only be randomized to a given approach but also to a surgeon, who is a recognized expert in that procedure.
We were unable to conduct any of the preplanned subgroup analyses, given the lack of appropriate data. However, it is possible that effects of age, neurovascular bundle sparing, cancer location, and other factors affected our findings. Specifically designed and adequately powered, high‐quality studies are necessary to elucidate these issues.
Given the importance of quality of life as an outcome, assessment of prostate cancer treatment‐related domains (such as urinary and sexual function) should be consistently collected and reported using a validated, prostate cancer‐specific instrument such as the Expanded Prostate Cancer Index Composite (EPIC) as developed by Wei and colleagues (Wei 2000).

Summary of findings

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Summary of findings 1. Retzius‐sparing RALP compared to standard RALP for the treatment of Prostate Cancer

Outcomes	No of participants (studies)	Certainty of the evidence (GRADE)	Relative effect (95% CI)	*Anticipated absolute effects (95% CI)**		Comment
Patient or population: men (ages > 18 years) with clinically localized prostate cancer Setting: inpatient setting Intervention: Retzius‐sparing RALP Comparison: standard RALP
Outcomes	No of participants (studies)	Certainty of the evidence (GRADE)	Relative effect (95% CI)	Risk with standard approach	Risk difference with Retzius‐sparing approach	Comment
Urinary continence within 1 week after catheter removal MCID: 5% absolute difference	410 (4 RCTs)	⊕⊕⊕⊝ Moderate^a	RR 1.74 (1.41 to 2.14)	Study population		RS‐RALP probably improves urinary continence within 1 week after catheter removal.
	410 (4 RCTs)	⊕⊕⊕⊝ Moderate^a	RR 1.74 (1.41 to 2.14)	335 per 1000	248 more per 1000 (137 more to 382 more)
Urinary continence 3 months after surgery MCID: 5% absolute difference	526 (5 RCTs)	⊕⊕⊝⊝ Low^a,b,c	RR 1.33 (1.06 to 1.68)	Study population		RS‐RALP may improve urinary continence 3 months after surgery.
	526 (5 RCTs)	⊕⊕⊝⊝ Low^a,b,c	RR 1.33 (1.06 to 1.68)	750 per 1000	224 more per 1000 (41 more to 462 more)
Serious adverse events Follow‐up: 12 months MCID: 2% absolute difference	230 (2 RCTs)	⊕⊝⊝⊝ Very low^a,d	RR 1.40 (0.47 to 4.17)	Study population		We are very uncertain about the effect on serious adverse events.
	230 (2 RCTs)	⊕⊝⊝⊝ Very low^a,d	RR 1.40 (0.47 to 4.17)	43 per 1000	17 more per 1000 (23 fewer to 138 more)
Urinary continence 12 months after surgery MCID: 5% absolute difference	222 (2 RCTs)	⊕⊕⊕⊝ Moderate^a	RR 1.01 (0.97 to 1.04)	Study population		RS‐RALP probably results in little to no difference in urinary continence 12 months after surgery.
	222 (2 RCTs)	⊕⊕⊕⊝ Moderate^a	RR 1.01 (0.97 to 1.04)	982 per 1000	10 more per 1000 (29 fewer to 39 more)
Potency 12 months after surgery MCID: 5% absolute difference	55 (1 RCT)	⊕⊝⊝⊝ Very low^a,d	RR 0.98 (0.54 to 1.80)	Study population		We are very uncertain about the effect on potency.
	55 (1 RCT)	⊕⊝⊝⊝ Very low^a,d	RR 0.98 (0.54 to 1.80)	440 per 1000	9 fewer per 1000 (202 fewer to 352 more)	We are very uncertain about the effect on potency.
Positive surgical margins MCID: 5% absolute difference	308 (3 RCTs)	⊕⊕⊝⊝ Low^a,e	RR 1.95 (1.19 to 3.20)	Study population		RS‐RALP may increase positive surgical margins.
Positive surgical margins MCID: 5% absolute difference	308 (3 RCTs)	⊕⊕⊝⊝ Low^a,e	RR 1.95 (1.19 to 3.20)	129 per 1000	123 more per 1000 (25 more to 284 more)	RS‐RALP may increase positive surgical margins.
Biochemical recurrence‐free survival Follow‐up: 12 months MCID: 2% absolute difference	218 (2 RCTs)	⊕⊝⊝⊝ Very low^a,d	HR 0.45 (0.13 to 1.60)	Study population		We are very uncertain about the effect on biochemical recurrence‐free survival.
	218 (2 RCTs)	⊕⊝⊝⊝ Very low^a,d	HR 0.45 (0.13 to 1.60)	86 per 1000	46 fewer per 1000 (74 fewer to 48 more)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HR: hazard ratio; MCID: minimal clinically important difference; MD: mean difference; PSM: positive surgical margin; RALP: robotic‐assisted laparoscopic prostatectomy; RCT: randomized controlled trial; RR: risk ratio; RS‐RALP: Retzius‐sparing robotic‐assisted laparoscopic prostatectomy.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level for study limitations: high or unclear risk of bias in half or more domains among included studies. ^bDowngraded one level for inconsistency due to substantial heterogeneity. ^cNot downgraded for imprecision since wide CI appeared secondary to inconsistency. ^dDowngraded two levels for imprecision: very wide confidence interval crossed assumed threshold of clinically important difference. ^eDowngraded one level for imprecision: confidence interval crosses assumed threshold of clinically important difference.

Background

Description of the condition

Prostate cancer is the most common solid organ malignancy in men (Siegel 2019). Main risk factors are age, family history, and ethnicity, with Black men at highest risk. Radical prostatectomy is a well‐established approach to treat clinically localized prostate cancer, with trial evidence showing improved long‐term oncologic outcomes compared to watchful waiting (Bill‐Axelson 2018; Wilt 2012; Wilt 2017). The procedure has mostly been performed using a radical retropubic approach; however, in recent years, robotic‐assisted laparoscopic prostatectomy (RALP) has become the main approach, in particular in the USA (Menon 2018; Sayyid 2017).

Common adverse events related to RALP include temporary and persistent urinary incontinence and erectile dysfunction (Ilic 2017; Ilic 2018), which may also adversely impact men's quality of life (Resnick 2013; Sanda 2008). Aside from patient factors such as body habitus and surgical anatomy, the surgical teams' skills and experience have been reported to impact prostatectomy outcomes in a major way (Vickers 2007). Continence outcomes are thought to be dependent upon anatomical factors: anatomical studies by Walz 2010 found that up to a 37% of the urethral sphincter area is laterally overlapped by the dorsal venous complex, which could be injured at the time of ligation and transection during standard RALP. The study also highlighted large anatomic variation of the internal pudendal artery, the internal gluteal artery, together with the frequency of the crossed vascularization in the retropubic space, which may be violated during standard RALP.

Surgical modifications that may assist with the recovery of continence include preserving the endopelvic fascia, puboprostatic ligaments, the neurovascular bundles, or a combination of these (Chang 2018). A variety of other technical modifications have also been described to enhance early recovery of urinary continence such as the so‐called Rocco stitch, bladder neck reconstruction and plication, and detrusorrhaphy (Shin 2019), but few have been assessed in well‐designed, randomized controlled trials (Checcucci 2020). A separate Cochrane Review on this topic is ongoing (Rosenberg 2020a).

Description of the intervention

Non‐Retzius‐sparing RALP replicates key surgical steps of open radical retropubic prostatectomy. The standard anterior surgical approach to RALP begins with dissecting the retropubic space between the pubic bone and the bladder, also known as the space of Retzius, to 'drop the bladder' and allow access to the dorsal venous complex and the prostatic apex.

Retzius‐sparing RALP (RS‐RALP) was first reported by urologists from Milan in 2010 (Galfano 2010); it avoids dissection of the retropubic space of Retzius and instead involves dissection of the posterior space of Douglas (recto‐vesical pouch). This mirrors some aspects of the classic open perineal approach by avoiding transection of the dorsal venous complex and preservation of the puboprostatic ligaments and endopelvic fascia, which may improve continence outcomes (Wiygul 2005). Perineal prostatectomy has favorable reported continence outcomes (Young 2003), but also involves transection of the perineal body and muscles of the pelvic floor, which RS‐RALP avoids. With both standard RALP and RS‐RALP, the entire prostate and seminal vesicles are removed, and the procedures can be performed with or without preservation of the neurovascular bundles.

It has also been argued that RS‐RALP is associated with a lower incidence of postoperative inguinal hernia (Chang 2017), avoids the retropubic space in men who have undergo an inguinal hernia repair with mesh, and would facilitate future procedures such as placement of a penile prosthesis, insertion of an artificial sphincter, and renal transplants if needed.

Adverse effects of the intervention

The RS‐RALP approach uses a smaller workspace, offers less and unfamiliar landmarks when it comes to the dissection of the lateral pedicles, makes it impossible to view the position of the ureteral orifices after bladder neck division, and challenges surgeons with an inverted relationship between bladder and prostate during dissection and reconstruction (Eden 2020). This dissection may be particularly challenging in men with a large prostate and those with locally advanced disease and may result in an extended learning curve (Stonier 2019). Potentially as a result, rates of positive surgical margins (PSM) may be higher in RS‐RALP versus standard RALP (Stonier 2019).

Other potential adverse effects of RS‐RALP are the same as those associated with standard RALP. Theoretically, the Retzius‐sparing (RS) technique may better preserve the anatomical structures related to continence, however, prolonged and persistent urinary incontinence can still occur. Other adverse effects of the intervention include erectile dysfunction, bladder neck contractures requiring secondary interventions, blood loss, and the need for transfusions and intraoperative injury to adjacent structures such as the rectum, small bowel, or large bowel.

How the intervention might work

RS‐RALP differs from the standard anterior approach by preserving the structural integrity of the anterior attachments of the bladder to the pubis, which may translate into earlier and better continence outcomes. This includes preservation of the dorsal venous complex, the puboprostatic ligaments, and the endopelvic fascia on both sides. It also maintains bladder suspension via the urachus and median umbilical ligaments, preventing bladder descent deeper into the pelvis (Egan 2020). Whereas the specific contribution of each of these anatomic structures is unclear, the assumption is that preservation of a more 'normal' anatomy aids the return of urinary continence. Also, one study has suggested that between 30% and 40% of the nervous fibers in the pelvic plexus, responsible for the neurologic mechanisms of the erection and the urinary continence, are located anterolaterally from the prostate presenting a disperse branching in the space of Retzius (Walz 2010). However, there is no consensus as to which anatomical structures are ultimately responsible for continence and whether the RS‐RALP better preserves relevant anatomical structures related to continence remains unknown.

Why it is important to do this review

A number of randomized and non‐randomized studies have compared RS‐RALP to standard RALP, and their results have been summarized in several systematic reviews (Checcucci 2020; Dirie 2019; Phukan 2020; Tai 2020). However, none have applied the same methodologic rigor as a Cochrane Review, which includes an a priori published protocol, an exhaustive search of the published and unpublished literature (irrespective of language of publication), a focus on patient‐important outcomes and clinically meaningful differences, and the use of the GRADE approach to assess the certainty of evidence for each outcome (Guyatt 2011). Our review therefore addresses an important gap in the knowledge on the effectiveness of RS‐RALP to guide clinical practice and future research. This can change the practice of urologic surgery to minimize the common adverse events after undergoing RALP. Findings of this review will help promote the further refinement and dissemination of a standardized approach to RALP.

Objectives

To assess the effects of RS‐RALP compared to standard RALP for the treatment of clinically localized prostate cancer.

Methods

Criteria for considering studies for this review

Types of studies

We included only parallel group randomized trials. We excluded cross‐over and cluster‐randomized trials as they are not relevant to this comparison and did not consider pseudo‐randomized controlled trials or observational studies given their increased risk of selection bias. We included studies regardless of their publication status or language of publication.

Types of participants

We included studies of men (aged 18 years or older) with clinically localized prostate cancer (clinical stage T1 to T2, N0, M0), who planned to undergo RALP.

We planned to exclude studies of men with pre‐existing urinary incontinence. Should we have identified studies in which only a subset of participants was relevant to this review, we planned to include such studies if data were available separately for the relevant subset.

Types of interventions

We investigated the following comparisons of experimental intervention versus comparator intervention. Concomitant interventions were included providing they were the same in the experimental and comparator groups.

Experimental interventions

Retzius‐sparing RALP.

Comparator interventions

Standard RALP.

Comparisons

Retzius‐sparing RALP versus standard RALP.

Types of outcome measures

We included studies regardless of whether they measured the outcomes to be assessed in this review.

Primary outcomes

Urinary continence within one week after catheter removal (dichotomous outcome).
Urinary continence three months after surgery (dichotomous outcome).
Serious adverse events (dichotomous outcome).

Secondary outcomes

Urinary continence six months after surgery (dichotomous outcome).
Urinary continence 12 months after surgery (dichotomous outcome).
Potency 12 months after surgery (dichotomous outcome).
Positive surgical margins (PSM) (dichotomous outcome).
Biochemical recurrence‐free survival (BCRFS) (time‐to‐event outcome).
Urinary function quality of life (continuous outcome).
Sexual function quality of life (continuous outcome).

Method and timing of outcome measurement

Urinary continence.
- Self‐reported absence of leakage or use of zero or one pads/day.
- We assessed this outcome up to 12 months after surgery.
- We considered a 5% absolute difference in continence rates as clinically important.
Serious adverse events.
- Measured as Dindo‐Clavien system grade III or more (Dindo 2004).
- We assessed this outcome up to 12 months after surgery.
- We considered a 2% absolute difference in serious adverse event rates as clinically important.
Potency.
- Number or percentage of participants achieving potency according to validated potency scales such as the International Index of Erectile Function (IIEF) and IIEF‐5 scores (Rosen 1997; Rosen 2011). We defined achieving potency as IIEF‐EF score of 19 or greater (mild erectile dysfunction) and IIEF‐5 score of 17 or greater (no erectile dysfunction).
- We assessed this outcome at 12 months after surgery.
- We considered a 5% absolute difference in potency rates as clinically important.
PSM.
- Positive when cancer cells were found at the ink‐marked resection margin.
- We assessed this outcome following surgery, on the basis of the prostatectomy specimen.
- We considered a 5% absolute difference in PSM as clinically important.
BCRFS.
- Defined as any prostate‐specific antigen (PSA) values of 0.2 ng/mL or greater (Heidenreich 2008).
- We will assess this outcome up to 60 months (five years) after surgery.
- We considered a 2% absolute difference in biochemical recurrence rates at 60 months as clinically important.
Urinary function quality of life.
- Final value or change assessed with validated questionnaires such as the urinary domain of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire (Wei 2000).
- We assessed this outcome up to 12 months after surgery.
- We considered a 5% absolute difference in quality of life as clinically important.
Sexual function quality of life.
- Final value or change assessed with validated questionnaires such as sexual domain of EPIC questionnaire (Wei 2000).
- We assessed this outcome up to 12 months after surgery.
- We considered a 5% absolute difference in quality of life as clinically important.

For all outcomes except potency, for which we found an established minimally clinically important difference (MCID) reported in the literature, all proposed thresholds were based on the clinical experience of the review authors.

Search methods for identification of studies

We performed a comprehensive search with no restrictions on the language of publication or publication status. We repeated searches within three months prior to anticipated publication of the review.

Electronic searches

We searched the following sources, from the inception of each database to 5 June 2020. Our search strategy is detailed in Appendix 1.

Cochrane Library via Wiley:
- NHS Economic Evaluation Database (NHS EED);
- Database of Abstracts of Reviews of Effects (DARE);
- Health Technology Assessment database (HTA).
MEDLINE via PubMed (from 1946).
MEDLINE via Ovid (from 1946).
Embase via Ovid (from 1947).
Web of Science Core Collection.
Scopus.
Global Index Medicus.

We also searched the following resources.

ClinicalTrials.gov (www.clinicaltrials.gov/).
World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (apps.who.int/trialsearch/).

If we detected additional relevant key words during any of the electronic or other searches, we modified the electronic search strategies to incorporate these terms and documented the changes.

Searching other resources

We tried to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, reviews, meta‐analyses, and health technology assessment reports. We also contacted study authors of included trials to identify any further studies that we may have missed. We contacted drug/device manufacturers for ongoing or unpublished trials.

We performed no hand searching for abstract proceedings, as all relevant meetings such as the American Urological Association, European Association of Urology, and Society of Urologic Oncology of the last three years (2018 to 2020) are published electronically and therefore were captured in our electronic search.

Data collection and analysis

Selection of studies

We used the reference management software Endnote to identify and remove potential duplicate records. Two review authors (JR, ZE, HL, or SL) independently scanned the abstract or title (or both) of remaining records retrieved, to determine which studies should be assessed further. Two review authors (JR, ZE) investigated all potentially relevant records as full text; they mapped records to studies and classified studies as included, excluded, awaiting classification, or ongoing, in accordance with the criteria for each provided in the most recent Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019). We resolved any discrepancies through consensus or recourse to a third review author (JHJ or PD). If resolution of a disagreement was not possible, we designated the study as 'awaiting classification' and contacted the study authors for clarification. We documented reasons for exclusion of studies that may have reasonably been expected to be included in the review in the Characteristics of excluded studies table. We presented a PRISMA flow diagram showing the process of study selection (Liberati 2009).

Data extraction and management

We developed a dedicated data extraction form that we pilot tested ahead of time. For studies that fulfill our inclusion criteria, two review authors (JR, ZE, HL, or SL) independently extracted the following information, which we provided in the Characteristics of included studies table.

Study design.
Study dates (if dates are not available then this was reported as such).
Study settings and country.
Participant inclusion and exclusion criteria (including tumor stage, PSA values, magnetic resonance imaging (MRI) findings).
Participant details, baseline demographics (age, comorbidities, body mass index).
Surgeons' characteristics (surgical experience).
The number of participants by study and by study arm.
Details of relevant RS‐RALP and standard RALP interventions (as applicable), for example, type and extent of nerve‐sparing technique, bladder neck reconstruction, etc.
Definitions of relevant outcomes, method and timing of outcome measurement and any relevant subgroups.
Study funding sources.
Declarations of interest by primary investigators.

We extracted outcome data relevant to this Cochrane Review as needed for calculation of summary statistics and measures of variance. For dichotomous outcomes, we attempted to obtain numbers of events and totals in order to populate a 2 × 2 table, as well as summary statistics with corresponding measures of variance. For continuous outcomes, we attempted to obtain means and standard deviations or data necessary to calculate this information. For time‐to‐event outcomes, we attempted to obtain hazard ratios (HRs) with corresponding measures of variance or data necessary to calculate this information.

We resolved any disagreements by discussion, or by consultation with a third review author (JHJ or PD), if required. We provided information, including trial identifier, about potentially relevant ongoing studies in the Characteristics of ongoing studies table. We attempted to contact authors of included studies to obtain key missing data as needed.

Dealing with duplicate and companion publications

In the event of duplicate publications, companion documents or multiple reports of a primary study, we maximized yield of information by mapping all publications to unique studies and collating all available data. We used the most complete dataset, aggregated across all known publications. In case of doubt, we gave priority to the publication reporting the longest follow‐up associated with our primary or secondary outcomes.

Assessment of risk of bias in included studies

Two review authors (JR, ZE, HL, or SL) independently assessed the risk of bias of each included study. We resolved disagreements by consensus, or by consultation with a third review author (JHJ or PD).

We assessed risk of bias using Cochrane's 'Risk of bias' assessment tool (Higgins 2017). We assessed the following domains.

Random sequence generation (selection bias).
Allocation concealment (selection bias).
Blinding of participants and personnel (performance bias).
Blinding of outcome assessment (detection bias).
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias).
Other sources of bias.

For each study, we judged the risk of bias for each domain as low, high, or unclear, using the guidance described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019). We presented a 'Risk of bias' summary figure to illustrate these findings.

For performance bias (blinding of participants and personnel) and detection bias (blinding of outcome assessment), we evaluated the risk of bias separately for each outcome, and grouped outcomes according to whether they were measured subjectively or objectively in the 'Risk of bias' table. We considered all outcomes as being similarly susceptible to performance bias. We judged the following endpoints as being susceptible to detection bias (i.e. subjective outcomes), thereby making blinding important.

Urinary continence (at various time points).
Serious adverse events.
Potency.
Urinary function quality of life.
Sexual function quality of life.

We judged the following endpoints as not susceptible to detection bias (i.e. objective outcomes), thereby making blinding unimportant.

PSM.
BCRFS.

We also assessed attrition bias (incomplete outcome data) on an outcome‐specific basis and presented the judgment for each outcome separately when reporting our findings in the 'Risk of bias' tables.

We further summarized the risk of bias across domains for each outcome in each included study, as well as across studies and domains for each outcome, in accordance with the approach for summary assessments of the risk of bias presented in the most recent Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019).

Measures of treatment effect

We expressed dichotomous data as risk ratios (RR) with 95% confidence intervals (CIs). We expressed continuous data as mean differences (MDs) with 95% CIs unless different studies used different measures to assess the same outcome, in which case we expressed data as standardized mean differences (SMDs) with 95% CIs. We expressed time‐to‐event data as HRs with 95% CIs.

Unit of analysis issues

The unit of analysis was the individual participant. If studies had multiple treatment arms, we planned to present any/all treatments that included RS‐RALP versus non‐RS‐RALP.

Dealing with missing data

We obtained missing data from study authors, when feasible, and performed intention‐to‐treat (ITT) analyses if data were available; we otherwise performed available‐case analyses. We investigated attrition rates, for example, dropouts, losses to follow‐up, and withdrawals, and critically appraised issues of missing data. We did not impute missing data.

Assessment of heterogeneity

We only performed meta‐analysis where this was meaningful, that is, the treatments, participants, and outcomes were similar enough. In the event of excessive heterogeneity unexplained by subgroup analyses, we did not report outcome results as the pooled effect estimate in a meta‐analysis but provided a narrative description of the results of each study.

We identified heterogeneity (inconsistency) through visual inspection of the forest plots to assess the amount of overlap of CIs, and by using the I² statistic, which quantifies inconsistency across studies to assess the impact of heterogeneity on the meta‐analysis (Deeks 2019; Higgins 2003). We interpreted the I² statistic as follows (Deeks 2019).

0% to 40%: may not be important.
30% to 60%: may indicate moderate heterogeneity.
50% to 90%: may indicate substantial heterogeneity.
75% to 100%: considerable heterogeneity.

When we identified heterogeneity, we attempted to determine possible reasons for it by examining individual study and subgroup characteristics.

Assessment of reporting biases

We attempted to obtain study protocols to assess for selective outcome reporting. If we had included 10 studies or more investigating a particular outcome, we would have used funnel plots to assess small‐study effects. Several explanations can be offered for the asymmetry of a funnel plot, including true heterogeneity of effect with respect to trial size, poor methodologic design (and hence bias of small trials), and publication bias. Therefore, we interpreted results carefully. We worked in line with recommendations within the Cochrane Handbook for Systematic Reviews of Interventions (Page 2019).

Data synthesis

Unless we found good evidence for homogeneous effects across studies, we summarized data using a random‐effects model. We interpreted random‐effects meta‐analyses with due consideration of the whole distribution of effects. In addition, we performed statistical analyses according to the statistical guidelines contained in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019). For dichotomous outcomes, we used the Mantel‐Haenszel method and for continuous and time‐to‐event outcomes, we used the generic inverse variance method. We used Review Manager 5 software to perform analyses (Review Manager 2014).

Subgroup analysis and investigation of heterogeneity

We expected the following characteristics to introduce clinical heterogeneity and planned to carry out subgroup analyses with investigation of interactions.

Participant age (less than 65 years versus 65 years and above). The decision to perform this subgroup analysis was based on studies suggesting the prognostic importance of age on continence recovery (Lavigueur‐Blouin 2015).
Nerve‐sparing approach (complete or partial nerve‐sparing versus non‐nerve‐sparing). The decision to perform this subgroup analysis was based on studies suggesting the prognostic importance of nerve‐sparing status on continence recovery (Sridhar 2017).
Clinical stage (cT1 versus cT2). The decision to perform this subgroup analysis was because oncologic outcomes such as time to biochemical recurrence and positive margins rates may vary based on clinical stage (Retèl 2014).

We used the test for subgroup differences in Review Manager 2014 to compare subgroup analyses if there were sufficient studies.

Sensitivity analysis

We planned to perform sensitivity analyses to explore the influence of the following factors (when applicable) on effect sizes.

Restricting the analysis by considering risk of bias, by excluding studies at high or unclear risk of bias.
Restricting the definition of continence to no pad use.

Summary of findings and assessment of the certainty of the evidence

We presented the overall certainty of the evidence for each outcome according to the GRADE approach, which takes into account criteria related to internal validity (risk of bias, inconsistency, imprecision, publication bias) and external validity (such as directness of results) (Guyatt 2008). For each comparison, two review authors (JR, ZE, HL, or SL) independently rated the certainty of evidence for each outcome as 'high', 'moderate', 'low', or 'very low' using GRADEpro GDT. We resolved any discrepancies by consensus, or, if needed, by arbitration by a third review author (JHJ or PD). For each comparison, we presented a summary of the evidence for the main outcomes in a 'Summary of findings' table, which provides key information about the best estimate of the magnitude of the effect in relative terms and absolute differences (with corresponding CLs presented in brackets) It for each relevant comparison of alternative management strategies; numbers of participants and studies addressing each important outcome; and the rating of the overall confidence in effect estimates for each outcome (Guyatt 2011; Schünemann 2011). If meta‐analysis was not possible, we presented results in a narrative 'Summary of findings' table.

Main outcomes for 'Summary of findings' table

We presented a 'Summary of findings' table reporting the following dichotomous outcomes (listed according to priority as determined by our clinical author panel).

Urinary continence within one week after catheter removal.
Urinary continence three months after surgery.
Serious adverse events.
Urinary continence 12 months after surgery.
Potency 12 months after surgery.
PSM.
BCRFS.

Results

Description of studies

Our search of multiple electronic databases yielded 271 references. We found no records through other sources.

Results of the search

After exclusion of duplicates, we screened 268 references at the title/abstract stage. Of these, eight references mapped to seven unique studies entered the full‐text screening stage. We excluded two studies because they are ongoing trials that have not provided usable outcome data at this time (see Characteristics of ongoing studies table). We ultimately included five studies in the quantitative analyses. This can be seen in our PRISMA flow diagram (Figure 1).

Figure 1

Study flow diagram.

Included studies

Source of data

We included two published studies (Asimakopoulos 2019; Dalela 2017), and three abstract proceedings (Bhat 2020; Kolontarev 2016; Qiu 2020). We contacted all authors and one of the authors of the abstract proceedings sent us their unpublished data (Qiu 2020). All included reports were published in English. We attempted to contact all corresponding authors of included trials to obtain additional information on study methods and results, and we received replies from three (Dalela 2017; Kolontarev 2016; Qiu 2020) (Appendix 2). Study characteristics are included in Table 1.

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Table 1. Study characteristics

Study	Age (years)	Clinical stage	Surgeon experience	No participants per arm	No participants receiving nerve sparing	Continence definition (pads/day)	Primary outcome	Secondary outcomes	Duration of follow‐up (months)
Asimakopoulos 2019	RS: 66 Standard: 65	cT1‐cT2, Gleason score ≤ 7, PSA ≤10 ng/mL	< 50 cases each technique	RS: 45 Standard: 57	RS: 39 (86.7%) Standard: 44 (77.1%)	0	Continence rates at catheter removal	PSM	6
Bhat 2020	N/A	T1 or T disease	> 400 cases	N/A	N/A	0	BCR, urinary continence return, erectile function	Operative time, blood loss, PSMs	12
Dalela 2017	RS: 60 Standard: 60	Low–intermediate risk (NCCN)	"varying levels of expertise" including residents and fellows	RS: 59 Standard: 60	RS: 37 (62.7%) Standard: 39 (65%)	0–1	Continence rates within 1 week of catheter removal	PSM, BCR, adverse events	12
Kolontarev 2016	Median age: 67.4	Not reported	N/A	RS: 39 Standard: 40	Not reported	0–1	Urinary continence within 1 week of catheter removal	Urinary bother symptoms	3
Qiu 2020	RS: 68 Standard: 67	low, intermediate, and high risk (EAU)	> 200 RS approach > 300 standard approach	RS: 55 Standard: 55	RS: 36 (65.5%) Standard: 38 (69.1%)	0	Urinary continence within 1 week of catheter removal	PSM, BCR, adverse events	12

BCR: biochemical recurrence; cT: clinical stage; EAU: European Association of Urology; PSA: prostate‐specific antigen; PSM: positive surgical margin; N/A: not applicable; NCCN: National Comprehensive Cancer Network; RALP: robotic‐assisted laparoscopic prostatectomy; RS: Retzius‐sparing.

Study design and settings

All studies were parallel single‐center randomized controlled trials (RCTs) in China (Qiu 2020), Europe (Asimakopoulos 2019; Kolontarev 2016), India (Bhat 2020), and the USA (Dalela 2017). Accrual periods ranged from 2011 to 2018.

Participants

We included 571 randomized participants, of whom 502 completed the trials (84.7%). One trial did not report the number of participants who completed the trial in each group (Kolontarev 2016). One trial did not report the number of participants who were randomized, but only reported the number of participants who were analyzed (Bhat 2020). Mean age ranged from 61 to 68 years. Common inclusion criteria were clinically localized prostate cancer and no pre‐existing urinary incontinence. Only one study included participants with high‐risk prostate cancer (Qiu 2020). A total of 233/331 participants received nerve‐sparing surgeries (70.4%), while no participants with high‐risk prostate cancer in Qiu 2020 received nerve sparing. Common exclusion criteria included extra‐prostatic disease and preoperative incontinence.

Intervention and comparator

All studies described an RS approach. Dalela 2017 and Qiu 2020 both used the surgical technique described by Galfano 2013. Dalela 2017 differed from this technique in that they used port placements similar to an anterior approach, did not perform seminal vesicle suspension, and routinely used a suprapubic tube. Qiu 2020 also deviated from this approach by not using seminal vesicle suspension and performing nerve sparing selectively only in men with low‐intermediate risk disease. Asimakopoulos 2019 used a similar technique to Galfano 2013 and used a Foley catheter. We only found the published abstract for Bhat 2020 and could not determine the surgical methods used.

Comparisons

All studies reported a 'standard' RALP as a comparator using a transperitoneal approach with selective nerve‐sparing. Asimakopoulos 2019 referred to the use of the Montsouris technique. Asimakopoulos 2019 also reported preservation of the puboprostatic ligaments. Dalela 2017 and Kolontarev 2016 both referred to the Vattikuti Institute technique (Bhandari 2007), and Qiu 2020 described using the approach attributed to Vipul Patel (Schatloff 2012). Bhat 2020 did not describe any details about the technique used.

Outcomes

Four studies reported urinary continence within one week of catheter removal while all five reported at three months. Four studies reported urinary continence at six months (Asimakopoulos 2019; Bhat 2020; Dalela 2017; Qiu 2020), while only Bhat 2020, Qiu 2020, and Dalela 2017 measured continence at 12 months after surgery. However, Bhat 2020 did not report usable data. Kolontarev 2016 did not report PSM rates and Bhat 2020 did not report usable data. Bhat 2020 measured but did not report freedom from biochemical recurrence while two studies reported freedom from biochemical recurrence (Dalela 2017; Qiu 2020). The median follow‐up time for BCRFS for Dalela 2017 was 13.5 months while for Qiu 2020 median follow‐up time was 12 months.

Two studies measured the recovery of potency (Bhat 2020; Dalela 2017), but only Dalela 2017 reported data. The study only included men who were potent preoperatively and were interested in sexual function postoperatively which resulted in 62/120 participants undergoing RALP. We used the study's definition of potency of Sexual Health Inventory for Men (SHIM) score of 17 or greater.

Dalela 2017 used scales and participant‐kept log sheets to document pad use after removing the suprapubic tube. Urinary function quality of life score was measured by International Prostate Symptom Score (IPSS) quality of life question. They used focal PSM (less than 2 mm). Asimakopoulos 2019 used the International Continence Society questionnaire to measure urinary continence and determined PSM when cancer cells were found in contact with the ink‐marked resection sample. To measure continence, Qiu 2020 used the EPIC questionnaire seven days after catheter removal and then by telephone interview thereafter. Qiu 2020 did not report how PSM was measured. Asimakopoulos 2019 and Kolontarev 2016 did not report the grade or severity of complications, while Dalela 2017 and Qiu 2020 used the Dindo‐Clavien scoring system. We used social continence (zero or one pads per day) whenever possible since we did not believe many men are comfortable using zero pads per day within one week after catheter removal. Dalela 2017 and Kolontarev 2016 both presented data for zero or one pads/day while Asimakopoulos 2019, Bhat 2020 and Qiu 2020 only presented data for zero pads/day. However, Dalela 2017 also reported the number of men using zero pads/day. We could not determine the methods to assess continence used for Bhat 2020.

Dalela 2017 and Qiu 2020 both reported serious adverse events using the Dindo‐Clavien classification system. Asimakopoulos 2019 also reported complications but did not provide sufficient detail to allow us to grade the severity; therefore, it was not included in the analysis.

Urinary function quality of life scores was determined by the quality‐of‐life question on the IPSS questionnaire. The response to the question "If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?" ranged from 0 ('Delighted') to 6 ('Terrible'), with 3 being 'Mixed'. This was treated as continuous (from 0 through 6). Dalela 2017 and Kolontarev 2016 both reported on this, but only Dalela 2017 reported usable data. No study reported sexual function quality of life.

Funding sources and conflicts of interest

None of the studies reported a funding source.

Excluded studies

We excluded no studies that entered the full‐text review stage.

Studies awaiting classification and ongoing trials

We identified no studies awaiting classification.

Ongoing studies

We found two ongoing studies that provided no usable outcome data (NCT03787823; NCT04393831); see Characteristics of ongoing studies table.

Risk of bias in included studies

For details, refer to the Characteristics of included studies table, 'Risk of bias' graph (Figure 2), and 'Risk of bias' summary (Figure 2) for the main comparison.

Figure 2

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

Allocation

Random sequence generation

Four studies reported an appropriate method and we rated them at low risk (Asimakopoulos 2019; Bhat 2020; Dalela 2017; Qiu 2020). One study failed to report sufficient detail to provide assurance of an adequate method of sequence generation and we rated it at unclear risk of bias.

Allocation concealment

Two studies documented an appropriate method of concealing allocation from the operating team and we rated these at low risk of bias (Dalela 2017; Qiu 2020). Three studies failed to document an appropriate method and we rated these at unclear risk of bias.

Blinding

Blinding of participants and personnel

It is not feasible to blind the surgeon or operating room personal, so we judged all five studies at high risk. Bhat 2020 and Qiu 2020 blinded their participants and postoperative caregivers; this was judged at low risk of bias. One study did not address the blinding of non‐operating room personal, so this was rated as unclear risk of bias (Kolontarev 2016). One study could not blind participants from their treatment allocation per hospital regulations and one study did not blind their participants or postoperative caregivers; these were at high risk of bias (Asimakopoulos 2019; Dalela 2017).

Blinding of outcome assessment

Subjective outcomes were urinary continence (at various time points), potency, urinary function, and sexual function quality of life. Two studies were at low risk because they blinded the participants and postoperative caregivers (Bhat 2020; Qiu 2020). The studies that did not address blinding participants were at unclear risk, while the studies that did not blind participants were at high risk for participant self‐assessed outcome assessment. The studies that did not address blinding non‐operating room personal were at unclear risk, while the studies that did not blind non‐operating room personal were rated at high risk for investigator‐adjudicated outcome assessment.

Objective outcomes were PSM and freedom from biochemical recurrence. We rated all studies at low risk for bias for these two outcomes because their measurement did not include any subjective judgment.

Incomplete outcome data

Urinary continence: four studies reported low levels of attrition that permitted a low risk of bias judgment (Asimakopoulos 2019; Bhat 2020; Dalela 2017; Qiu 2020). For the remaining study, it was unclear whether all randomized participants were included in the analysis. Therefore, they were at unclear risk.
Serious adverse events: three studies reported low levels of attrition that permitted a low risk of bias judgment (Asimakopoulos 2019; Dalela 2017; Qiu 2020). The remaining studies did not present this data.
Potency: three studies did not report on potency (Asimakopoulos 2019; Kolontarev 2016; Qiu 2020), while the one study that did report had an attrition rate of 11.3%, which we rated at unclear risk of bias (Dalela 2017). For the remaining study, it is unclear whether all randomized participants were included in the analysis (Bhat 2020). Therefore, it was judged at unclear risk.
Oncologic outcomes: three studies reported low levels of attrition that permitted a low risk of bias judgment (Asimakopoulos 2019; Dalela 2017; Qiu 2020). The remaining studies did not present these data. For one study, it was unclear whether all randomized participants were included in the analysis. Therefore, it was judged at unclear risk. The remaining study did not present these data.
Quality of life: one study reported low level of attrition that permitted a low risk of bias judgment (Dalela 2017). The remaining studies did not present this data.

Selective reporting

One of the five studies reported outcomes analyses consistent with a priori, registered protocol; therefore, we rated this study at low risk of bias (Dalela 2017). One study did not report the potency outcome consistent with a priori, registered protocol; therefore, we rated this at unclear risk of bias (Qiu 2020).

We found no a priori written protocol for the remaining three included studies. We rated them one of them at unclear risk of bias because we have no assurance that all measured outcomes were reported and analyzed as intended (Asimakopoulos 2019); two studies we rated as high risk of bias because reporting was largely limited to abstracts only (Bhat 2020; Kolontarev 2016).

Other potential sources of bias

We found no other sources of bias for all included studies, and we rated them at low risk for this domain.

Effects of interventions

See: Summary of findings 1 Retzius‐sparing RALP compared to standard RALP for the treatment of Prostate Cancer

1 Retzius‐sparing robotic‐assisted laparoscopic prostatectomy versus standard robotic‐assisted laparoscopic prostatectomy

Five studies compared RS‐RALP versus standard RALP (summary of findings Table 1).

1.1 Urinary continence within one week after catheter removal

RS‐RALP probably increases recovery of urinary continence within one week after catheter removal compared to standard RALP (RR 1.74, 95% CI 1.41 to 2.14; I² = 0%; studies = 4; participants = 410; moderate‐certainty evidence; Analysis 1.1). Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 248 more per 1000 (137 more to 382 more) men reporting urinary continence with RS‐RALP. We downgraded the certainty of the evidence for serious study limitations.

1.2 Urinary continence three months after surgery

RS‐RALP may increase recovery of urinary continence three months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06 to 1.68; I² = 86%; studies = 5; participants = 526; low‐certainty evidence; Analysis 1.2). Assuming 750 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 224 more per 1000 (41 more to 462 more) men reporting urinary continence with RS‐RALP. We downgraded the certainty of the evidence for serious study limitations and serious inconsistency.

1.3 Serious adverse events

We are very uncertain about the effect of RS‐RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47 to 4.17; I² = 0%; studies = 2; participants = 230; very low‐certainty evidence; Analysis 1.3). We downgraded the certainty of the evidence for serious study limitations and very serious imprecision.

1.4 Urinary continence six months after surgery

RS‐RALP may increase recovery of urinary continence six months after surgery compared to standard RALP (RR 1.09, 95% CI 0.99 to 1.20; I² = 62%; studies = 4; participants = 447; low‐certainty evidence; Analysis 1.4). Assuming 851 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 77 more per 1000 (9 fewer to 170 more) men reporting urinary continence recovery with RS‐RALP. We downgraded the certainty of the evidence for serious study limitations and serious inconsistency.

1.5 Urinary continence 12 months after surgery

RS‐RALP probably results in little to no difference in urinary continence 12 months after surgery compared to standard RALP (RR 1.01, 95% CI 0.97 to 1.04; I² = 0%; studies = 2; participants = 222; moderate‐certainty evidence; Analysis 1.5). Assuming 982 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 10 more per 1000 (29 fewer to 39 more) men reporting urinary continence recovery with RS‐RALP. We downgraded the certainty of the evidence for serious study limitations.

1.6 Potency 12 months after surgery

We are very uncertain about the effect of RS‐RALP on potency 12 months after surgery compared to standard RALP (RR 0.98, 95% CI 0.54 to 1.80; I² = 0%; studies = 1; participants = 55; very low‐certainty evidence; Analysis 1.6). We downgraded the certainty of the evidence for serious study limitations and very serious imprecision.

1.7 Positive surgical margins

RS‐RALP may increase PSM compared to standard RALP (RR 1.95, 95% CI 1.19 to 3.20; I² = 0%; studies = 3; participants = 308; low‐certainty evidence; Analysis 1.7). Assuming 129 per 1000 men undergoing standard RALP have positive margins, this corresponds to 123 more per 1000 (25 more to 284 more) men with PSM with RS‐RALP. We downgraded the certainty of the evidence for serious study limitations and serious imprecision.

1.8 Biochemical recurrence‐free survival

We are very uncertain about the effect of RS‐RALP on BCRFS compared to standard RALP (HR 0.45, 95% CI 0.13 to 1.60; studies = 2; participants = 218; very low‐certainty evidence; Analysis 1.8). We downgraded the certainty of the evidence for study limitations and very serious imprecision.

1.9 Urinary function quality of life three months after surgery

RS‐RALP may improve urinary function quality of life compared to standard RALP using the IPSS quality of life scale (0 to 6; higher value reflect more bother/worse quality of life) (MD –0.60, 95% CI –1.12 to –0.08; studies = 1; participants = 119; low‐certainty evidence; Analysis 1.9). We downgraded the certainty of the evidence for serious study limitations and serious imprecision given that the 95% CI crossed the assumed threshold of a 0.5 point change in IPSS‐Quality of Life.

1.10 Sexual function quality of life

None of the studies reported sexual function quality of life and thus no analysis could be performed.

Subgroup analyses

We were unable to conduct the preplanned subgroup analyses based on participant age, nerve‐sparing status, or clinical stage due to a lack of data to analyze.

Sensitivity analyses

Based on risk of bias

We were unable to conduct the preplanned sensitivity analyses by excluding studies at high or unclear risk of bias given the paucity of study and the similar risk of bias profiles.

Based on definition of continence of no pad use

1.11 Urinary continence within one week after catheter removal

Findings were similar: RS‐RALP probably increases recovery of urinary continence within one week after catheter removal compared to standard RALP (RR 2.18, 95% CI 1.63 to 2.92; I² = 0%; studies = 3; participants = 331).

1.12 Urinary continence three months after surgery

Findings were similar: RS‐RALP may increase recovery of urinary continence three months after surgery compared to standard RALP (RR 1.33, 95% CI 1.17 to 1.52; I² = 0%; studies = 5; participants = 327).

1.13 Urinary continence six months after surgery

Findings were similar: RS‐RALP may increase recovery of urinary continence six months after surgery compared to standard RALP (RR 1.16, 95% CI 0.96 to 1.41; I² = 77%; studies = 3; participants = 327).

1.14 Urinary continence 12 months after surgery

Findings were similar: RS‐RALP probably results in little to no difference in urinary continence 12 months after surgery compared to standard RALP (RR 1.03, 95% CI 0.97 to 1.17; I² = 76%; studies = 2; participants = 222).

Discussion

Summary of main results

Findings of this study are based on five RCTs that randomized 571 men with clinically localized prostate cancer. All participants (mean age: 64.6 years) had either cT1c or cT2 disease with a mean PSA of 6.9 ng/mL. Three studies were available as full‐text (Asimakopoulos 2019; Dalela 2017; Qiu 2020); two as abstract only (Bhat 2020; Kolontarev 2016), and only one study (Dalela 2017) had an a priori registered protocol.

We found that RS‐RALP probably results in earlier continence recovery one week after catheter removal (moderate‐certainty evidence) and may also do so three months (low‐certainty evidence) and six months (low‐certainty evidence) after surgery. Urinary quality of life at three months (measured by the IPSS‐Quality of Life item) may also be improved (low‐certainty evidence). At 12 months, there may be no difference in continence outcomes (low‐certainty evidence).

Based on the available evidence, we are very uncertain about the effect on serious adverse events (very low‐certainty evidence). We are also very uncertain about potency at 12 months (very low‐certainty evidence). Meanwhile, RS‐RALP may result in higher rates of positive surgical margins (low‐certainty evidence) and we are very uncertain about the effect on BCRFS (very low‐certainty evidence) compared to standard RALP.

This review was unable to determine if or how these findings may be impacted by patient age, nerve‐sparing status, clinical stage, or a combination of these. Continence outcomes were robust to sensitivity analyses based on a more stringent continence definition of no pads.

Overall completeness and applicability of evidence

This systematic review represents the most rigorous and up‐to‐date systematic review on the question of RS‐RALP. Although we perceive this body of evidence to be broadly applicable to current clinical practice, the following issues deserve mention.

RS‐RALP is a relatively new, potentially evolving surgical approach whereas standard RALP is a well‐established and mature approach. The reported experience may reflect the early phase of the surgical experience and learning curve of the surgical team, which have been important predictors of outcomes thereby limiting the applicability of this review's findings (Vickers 2009). There is also concern about performance bias, which ideally would be addressed by an expertise‐based trial (Devereaux 2005; Scholtes 2012), in which participants are not only randomized to a given procedure but also an expert surgeon.
A critical limitation of this study is the lack of long‐term oncologic outcomes. Findings of this review are limited to PSM and BCRFS around 12 months after surgery, which both represent surrogate outcomes for disease‐specific survival. Based on these findings, claims of comparable oncologic outcomes appear premature (Egan 2020). Extended follow‐up from existing and future studies may provide more information.
Four studies enrolled participants with primarily low‐ and intermediate‐risk prostate cancer (Asimakopoulos 2019; Bhat 2020; Dalela 2017; Kolontarev 2016); therefore, findings of this review are most applicable to that patient population. There is concern that oncologic outcomes could be further compromised in men with high‐risk disease undergoing a RS‐RALP. Due to the lack of data, we were unable to perform a preplanned subgroup analysis based on clinical stage.
Similarly, we were unable to perform subgroup analyses based on patient age and nerve‐sparing, which are both potential effect modifiers. This may have helped to explain some of the observed statistical heterogeneity, in particular for the outcome of urinary continence at three months (Analysis 1.2) and six months (Analysis 1.4) after surgery. Surgical technique likely differed at least to some degree across studies both for the intervention (e.g. Dalela 2017 was the only study to routinely use a suprapubic catheter instead of a Foley catheter) and in the standard RALP group, resulting in clinical heterogeneity. Prior studies suggest that surgical technique for standard RALP can vary greatly (Wu 2020).
Findings of this review were limited by the lack of information about both clinical and methodologic details of included studies. Only one study had a registered, a priori protocol (Dalela 2017). Two studies were only available in abstract form and provided particularly scarce clinical and methodologic details (Bhat 2020; Kolontarev 2016). Our attempts to contact the authors to obtain additional information were unsuccessful. We included these studies to guard against publication bias.
A number of modifications of the standard RALP have been explored to improve continence outcomes, most notable techniques of posterior reconstruction, which a companion Cochrane Review is exploring (Rosenberg 2020a). Recent innovations have focused on anterior preservation by virtue of a modified apical dissection and lateral prostatic fascia preservation (Moschovasa 2020), and the detrusor apron sparing hood (DASH) technique (Cumarasamy 2019). These modifications were not applied in the standard RALP arms of studies included in this review (neither has their value been rigorously evaluated in the context of RCTs).

Quality of the evidence

The certainty of the evidence rating on a per‐outcome basis ranged from moderate to very low, indicating that we downgraded each outcome at least once. The most common reasons for downgrading were:

study limitations: allocation concealment was frequently unclear raising concerns about selection bias. None of the studies used an expertise‐based trial design to guard against performance bias on part of the surgeon (who could not be blinded for obvious reasons). Most studies left it at least unclear whether non‐operating room personnel were blinded and whether investigators of subjective outcomes such as continence were blinded, further raising concerns about performance and detection bias. Based on these observations, we consistently rated down all outcomes by at least one level for study limitations;
inconsistency: for the outcomes of urinary continence at three and six months, we observed clinically relevant heterogeneity that we could not explain further by any of our preplanned subgroup analyses. This led to rating down for inconsistency of these two outcomes;
imprecision: wide CIs that crossed the threshold of clinical relevance led to us to downgrade the certainty of the evidence two levels (serious adverse events, potency, BCRFS) or one level (PSM). However, when apparent imprecision could plausibly be explained by inconsistency (which prompted downgrading), we did not downgrade further.

Potential biases in the review process

The study was performed based on rigorous Cochrane standards, which included a published protocol (Rosenberg 2020b). Nevertheless, certain issues could be a source of bias.

We performed a comprehensive literature search for eligible studies irrespective of language and publication status. Nevertheless, we may have missed studies, in particular 'negative' studies published in languages other than English or in non‐indexed journals, or both. Too few studies were included in the meta‐analyses to formally assess for publication bias using a Funnel plot or other statistical tests.
This review included five randomized controlled trials of which three (Asimakopoulos 2019; Dalela 2017; Qiu 2020) were available as full‐text reports. Two included studies (Bhat 2020, Kolontarev 2016) were available as abstracts only, although we were able to obtain additional information through direct communication. Nevertheless, we recognize the importance of selective reporting bias.
Included studies reported participants' urinary continence at different time points. To provide meaningful summary data that might be helpful for clinicians and patients, we grouped available data by four time periods of within one week after catheter removal, three months after surgery, six months after surgery, and one year after surgery. These categories we established with input by expert clinicians before the protocol was written, data were abstracted, and any quantitative analysis was performed. Nevertheless, findings for these outcomes are potentially sensitive to the specific time ranges we chose, and this may be viewed as a potential source of bias.
Our interpretations of the magnitudes of effects for both desirable and undesirable outcomes as well as judgments about the certainty of evidence when it comes to the domains of imprecision and inconsistency hinge on assumptions about MCID. This is in the context of a minimally contextualized approach based on GRADE guidance (Hultcrantz 2017). Unless validated instruments were used and published MCIDs were available, the thresholds used were based on the input by the clinical co‐authors and have sought to do so transparently. We recognize that the use of different thresholds would somewhat alter the conclusions of this review.

Agreements and disagreements with other studies or reviews

To date, no review has applied the rigorous Cochrane methodology to this topic. Defining characteristics of this review included an a priori protocol (Rosenberg 2020b), a comprehensive literature search irrespective of language and publication status, a focus on patient‐centered outcomes, and the application of GRADE methodology. Furthermore, our interpretation focused on clinically relevant (rather than statistically significant) findings and provided absolute effect size estimates for all dichotomous outcomes. This is also the most up‐to‐date review that included data from studies that have only become available in their abstract form or seeking unpublished data from the authors (Bhat 2020; Kolontarev 2016; Qiu 2020).

Checcucci 2020 reported a systematic review that stands out favorably by the existence of an a priori registered protocol. It included two RCTS (Asimakopoulos 2019; Dalela 2017), and five non‐RCTS (Chang 2014; Chang 2018; Eden 2018; Mistretta 2019; Sayyid 2017). Rather than analyzing both bodies of evidence separately, the authors opted to pool across all studies, which is not recommended. It found similar results to our review with regard to several outcomes, namely improved continence recovery rate at one, three, six, and 12 months defining continence as zero or one pad per day in favor of the RS‐RALP (1 month: OR 2.54, 95% CI 1.16 to 5.53; 3 months: OR 3.86, 95% CI 2.23 to 6.68; 6 months: OR 3.61, 95% CI 1.88 to 6.91; 12 months: OR 7.29, 95% CI 1.89 to 28.13). They also found a higher risk of PSM (OR 1.71, 95% CI 1.12 to 2.60), but did not report results for BCRFS. None of the outcomes were qualified by a certainty of evidence rating, which we would view as a critical element of any systematic review.
Phukan 2020 is the most recent systematic review but its latest literature search was performed in December 2018. It did not reference an a priori protocol. It included the same two RCTs (Asimakopoulos 2019; Dalela 2017), and four non‐RCTs (Chang 2014; Chang 2018; Eden 2018; Sayyid 2017). These authors also pooled across both bodies of evidence without assessing them separately beforehand, then dropping the certainty of the evidence down to 'very low' for all analyses that incorporated data from non‐RCTs. This is not in accordance with GRADE guidance and resulted in the appearance of greater uncertainty than found in our review. The authors' main conclusion was that RS‐RARP appears to have earlier continence recovery when compared to conventional RARP, which does not come at a significant oncologic cost, despite point estimates suggesting higher PSM rates and inferior biochemical recurrence‐free survival. We see this difference in interpretation as the result of using a non‐contextualized result interpretation that focused primarily on statistical rather than clinical significance.
Tai 2020 reported a systematic review that lacked a protocol, excluded unpublished studies and included the same two RCTS (Asimakopoulos 2019; Dalela 2017) and four non‐RCTS (Chang 2014; Chang 2018; Eden 2018; Sayyid 2017) as Phukan 2020. It also pooled across all studies indiscriminately and did not rate the certainty of the evidence on a per outcome basis.
One retrospective, propensity score matched study by Lee 2020 did not meet inclusion criteria of this review but stood out by virtue of sample size, which represents the largest single center experience of 713 men undergoing this approach. It focused on short‐term continence outcomes at one, three, and six months after surgery which all favored the RS‐approach. Any information on PSM and BCFS were notably absent from this study.

Figure 1

Study flow diagram.

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Figure 2

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 1: Urinary continence within 1 week after catheter removal

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Analysis 1.2

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 2: Urinary continence 3 months after surgery

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Analysis 1.3

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 3: Serious adverse events

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Analysis 1.4

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 4: Urinary continence 6 months after surgery

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Analysis 1.5

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 5: Urinary continence 12 months after surgery

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Analysis 1.6

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 6: Potency recovery 12 months after surgery

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Analysis 1.7

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 7: Positive surgical margins

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Analysis 1.8

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 8: Biochemical recurrence‐free survival

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Analysis 1.9

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 9: Urinary function quality of life 3 months after catheter removal

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Analysis 1.10

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 10: Sensitivity analysis: urinary continence within 1 week after catheter removal (0 pads)

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Analysis 1.11

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 11: Sensitivity analysis: urinary continence 3 months after surgery (0 pads)

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Analysis 1.12

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 12: Sensitivity analysis: urinary continence 6 months after surgery (0 pads)

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Analysis 1.13

Comparison 1: Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP), Outcome 13: Sensitivity analysis: urinary continence 12 months after surgery (0 pads)

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Summary of findings 1. Retzius‐sparing RALP compared to standard RALP for the treatment of Prostate Cancer

Outcomes	No of participants (studies)	Certainty of the evidence (GRADE)	Relative effect (95% CI)	*Anticipated absolute effects (95% CI)**		Comment
Patient or population: men (ages > 18 years) with clinically localized prostate cancer Setting: inpatient setting Intervention: Retzius‐sparing RALP Comparison: standard RALP
Outcomes	No of participants (studies)	Certainty of the evidence (GRADE)	Relative effect (95% CI)	Risk with standard approach	Risk difference with Retzius‐sparing approach	Comment
Urinary continence within 1 week after catheter removal MCID: 5% absolute difference	410 (4 RCTs)	⊕⊕⊕⊝ Moderate^a	RR 1.74 (1.41 to 2.14)	Study population		RS‐RALP probably improves urinary continence within 1 week after catheter removal.
	410 (4 RCTs)	⊕⊕⊕⊝ Moderate^a	RR 1.74 (1.41 to 2.14)	335 per 1000	248 more per 1000 (137 more to 382 more)
Urinary continence 3 months after surgery MCID: 5% absolute difference	526 (5 RCTs)	⊕⊕⊝⊝ Low^a,b,c	RR 1.33 (1.06 to 1.68)	Study population		RS‐RALP may improve urinary continence 3 months after surgery.
	526 (5 RCTs)	⊕⊕⊝⊝ Low^a,b,c	RR 1.33 (1.06 to 1.68)	750 per 1000	224 more per 1000 (41 more to 462 more)
Serious adverse events Follow‐up: 12 months MCID: 2% absolute difference	230 (2 RCTs)	⊕⊝⊝⊝ Very low^a,d	RR 1.40 (0.47 to 4.17)	Study population		We are very uncertain about the effect on serious adverse events.
	230 (2 RCTs)	⊕⊝⊝⊝ Very low^a,d	RR 1.40 (0.47 to 4.17)	43 per 1000	17 more per 1000 (23 fewer to 138 more)
Urinary continence 12 months after surgery MCID: 5% absolute difference	222 (2 RCTs)	⊕⊕⊕⊝ Moderate^a	RR 1.01 (0.97 to 1.04)	Study population		RS‐RALP probably results in little to no difference in urinary continence 12 months after surgery.
	222 (2 RCTs)	⊕⊕⊕⊝ Moderate^a	RR 1.01 (0.97 to 1.04)	982 per 1000	10 more per 1000 (29 fewer to 39 more)
Potency 12 months after surgery MCID: 5% absolute difference	55 (1 RCT)	⊕⊝⊝⊝ Very low^a,d	RR 0.98 (0.54 to 1.80)	Study population		We are very uncertain about the effect on potency.
	55 (1 RCT)	⊕⊝⊝⊝ Very low^a,d	RR 0.98 (0.54 to 1.80)	440 per 1000	9 fewer per 1000 (202 fewer to 352 more)	We are very uncertain about the effect on potency.
Positive surgical margins MCID: 5% absolute difference	308 (3 RCTs)	⊕⊕⊝⊝ Low^a,e	RR 1.95 (1.19 to 3.20)	Study population		RS‐RALP may increase positive surgical margins.
Positive surgical margins MCID: 5% absolute difference	308 (3 RCTs)	⊕⊕⊝⊝ Low^a,e	RR 1.95 (1.19 to 3.20)	129 per 1000	123 more per 1000 (25 more to 284 more)	RS‐RALP may increase positive surgical margins.
Biochemical recurrence‐free survival Follow‐up: 12 months MCID: 2% absolute difference	218 (2 RCTs)	⊕⊝⊝⊝ Very low^a,d	HR 0.45 (0.13 to 1.60)	Study population		We are very uncertain about the effect on biochemical recurrence‐free survival.
	218 (2 RCTs)	⊕⊝⊝⊝ Very low^a,d	HR 0.45 (0.13 to 1.60)	86 per 1000	46 fewer per 1000 (74 fewer to 48 more)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HR: hazard ratio; MCID: minimal clinically important difference; MD: mean difference; PSM: positive surgical margin; RALP: robotic‐assisted laparoscopic prostatectomy; RCT: randomized controlled trial; RR: risk ratio; RS‐RALP: Retzius‐sparing robotic‐assisted laparoscopic prostatectomy.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level for study limitations: high or unclear risk of bias in half or more domains among included studies. ^bDowngraded one level for inconsistency due to substantial heterogeneity. ^cNot downgraded for imprecision since wide CI appeared secondary to inconsistency. ^dDowngraded two levels for imprecision: very wide confidence interval crossed assumed threshold of clinically important difference. ^eDowngraded one level for imprecision: confidence interval crosses assumed threshold of clinically important difference.

Summary of findings 1. Retzius‐sparing RALP compared to standard RALP for the treatment of Prostate Cancer

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Table 1. Study characteristics

Study	Age (years)	Clinical stage	Surgeon experience	No participants per arm	No participants receiving nerve sparing	Continence definition (pads/day)	Primary outcome	Secondary outcomes	Duration of follow‐up (months)
Asimakopoulos 2019	RS: 66 Standard: 65	cT1‐cT2, Gleason score ≤ 7, PSA ≤10 ng/mL	< 50 cases each technique	RS: 45 Standard: 57	RS: 39 (86.7%) Standard: 44 (77.1%)	0	Continence rates at catheter removal	PSM	6
Bhat 2020	N/A	T1 or T disease	> 400 cases	N/A	N/A	0	BCR, urinary continence return, erectile function	Operative time, blood loss, PSMs	12
Dalela 2017	RS: 60 Standard: 60	Low–intermediate risk (NCCN)	"varying levels of expertise" including residents and fellows	RS: 59 Standard: 60	RS: 37 (62.7%) Standard: 39 (65%)	0–1	Continence rates within 1 week of catheter removal	PSM, BCR, adverse events	12
Kolontarev 2016	Median age: 67.4	Not reported	N/A	RS: 39 Standard: 40	Not reported	0–1	Urinary continence within 1 week of catheter removal	Urinary bother symptoms	3
Qiu 2020	RS: 68 Standard: 67	low, intermediate, and high risk (EAU)	> 200 RS approach > 300 standard approach	RS: 55 Standard: 55	RS: 36 (65.5%) Standard: 38 (69.1%)	0	Urinary continence within 1 week of catheter removal	PSM, BCR, adverse events	12
BCR: biochemical recurrence; cT: clinical stage; EAU: European Association of Urology; PSA: prostate‐specific antigen; PSM: positive surgical margin; N/A: not applicable; NCCN: National Comprehensive Cancer Network; RALP: robotic‐assisted laparoscopic prostatectomy; RS: Retzius‐sparing.

Table 1. Study characteristics

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Comparison 1. Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Urinary continence within 1 week after catheter removal Show forest plot	4	410	Risk Ratio (M‐H, Random, 95% CI)	1.74 [1.41, 2.14]

1.2 Urinary continence 3 months after surgery Show forest plot	5	526	Risk Ratio (M‐H, Random, 95% CI)	1.33 [1.06, 1.68]

1.3 Serious adverse events Show forest plot	2	230	Risk Ratio (M‐H, Random, 95% CI)	1.40 [0.47, 4.17]

1.4 Urinary continence 6 months after surgery Show forest plot	4	447	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.99, 1.20]

1.5 Urinary continence 12 months after surgery Show forest plot	2	222	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.97, 1.04]

1.6 Potency recovery 12 months after surgery Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

1.7 Positive surgical margins Show forest plot	3	308	Risk Ratio (M‐H, Random, 95% CI)	1.95 [1.19, 3.20]

1.8 Biochemical recurrence‐free survival Show forest plot	2	218	Hazard Ratio (IV, Random, 95% CI)	0.45 [0.13, 1.60]

1.9 Urinary function quality of life 3 months after catheter removal Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

1.10 Sensitivity analysis: urinary continence within 1 week after catheter removal (0 pads) Show forest plot	3	331	Risk Ratio (M‐H, Random, 95% CI)	2.18 [1.63, 2.92]

1.11 Sensitivity analysis: urinary continence 3 months after surgery (0 pads) Show forest plot	3	327	Risk Ratio (M‐H, Random, 95% CI)	1.33 [1.17, 1.52]

1.12 Sensitivity analysis: urinary continence 6 months after surgery (0 pads) Show forest plot	3	327	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.96, 1.41]

1.13 Sensitivity analysis: urinary continence 12 months after surgery (0 pads) Show forest plot	2	222	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.91, 1.17]

Comparison 1. Retzius‐sparing (RS‐RALP) versus standard robotic‐assisted laparoscopic prostatectomy (RALP)

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Cochrane Review language

Website language

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

PICOs

PICOs

Population

Intervention

Comparison

Outcome

Plain language summary

Should we perform Retzius‐sparing RALP or standard RALP for clinically localized prostate cancer?

Visual summary

Authors' conclusions

Implications for practice

Implications for research

Summary of findings

Background

Description of the condition

Description of the intervention

Adverse effects of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Experimental interventions

Comparator interventions

Comparisons

Types of outcome measures

Primary outcomes

Secondary outcomes

Method and timing of outcome measurement

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Dealing with duplicate and companion publications

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Main outcomes for 'Summary of findings' table

Results

Description of studies

Results of the search

Included studies

Source of data

Study design and settings

Participants

Intervention and comparator

Comparisons

Outcomes

Funding sources and conflicts of interest

Excluded studies

Studies awaiting classification and ongoing trials

Ongoing studies

Risk of bias in included studies

Allocation

Random sequence generation

Allocation concealment

Blinding

Blinding of participants and personnel