Global variation in the long-term outcomes of ypT0 rectal cancers☆
Introduction
Recent data from the Global Cancer Observatory (GLOBOCAN 2018), documented that colorectal cancer is still the third most frequent cancer and the second cause of cancer related mortality, however its incidence and mortality present a relevant world-wide variation [1,2].
Rectal cancers account for about 30% of colorectal cancers [3] and represent a field of relevant surgical, clinical and biological investigations. Over the last three decades the approach to rectal cancer radically changed: the improvements achieved lead to the introduction of total mesorectal excision (TME) and neoadjuvant (chemo)radiation treatments [4,5]. Nevertheless, the state-of-the art is continuously evolving as the effects of neoadjuvant treatments started to emerge in literature [6].
In particular, tumor down-staging following neoadjuvant treatment could result in a complete response, defined as clinical response (absence of residual primary tumor clinically detectable, cT0) or pathological response (absence of viable tumor cells within the rectal wall in the surgical specimen, ypT0) [7], occurring in about 10–20% of the patients who were treated with neoadjuvant therapy prior to surgery [8,9].
In this subset of patients, the improved survival outcomes [10,11] and the benefits of avoiding major surgical procedures, are encouraging a more conservative approach including watch and wait protocols [12,13] or a local excision of the residual tumor scar [14].
Despite the achievement of a complete response could be acknowledged as a milestone, a number of issues still need to be addressed, in particular in relation to the surgical strategy, the identification of factors correlated to relapses and tumor regression, and the incidence and impact of a residual nodal disease.
A pilot multicenter investigation was recently conducted in this field investigating the pattern of survivals of rectal cancer patients presenting a complete or nearly complete tumor response after neoadjuvant therapy. Patients were treated using local excision or TME in Italy and Spain and results were highly promising, in particular in disclosing differences in survivals between patients assessed as nodal negative (ypN0) or presenting residual nodal metastases (ypN+) [6].
On the other hand, significant differences are emerging concerning survivals of rectal cancers in different countries, surprising also when comparing Norther European countries [15]. The geographic discrepancies concerning surgical quality and access to surgical care are currently a prioritizing issue, as widely declared by the Lancet Commission on Global Surgery [16]. On this extent, the National Institute for Health Research (NIHR) Global Health Research Unit on Global Surgery is in the process of establishing research hubs in low- and middle-income countries; a four-stage modified Delphy study identified three priority areas for future research, including the access to surgery, surgical oncology and peri-operative surgical care. With respect to the second domain, the aim was to define a resource-weighted quality assurance framework for cancer surgery; the research questions included, among the others, the identification of quality indicators and the role of multidisciplinary team meeting (MDT) in delivering cancer care. Accordingly, it was agreed that “a global observational cohort study was needed to benchmark care pathways and outcomes in low-income against high-income countries. This study would capture data on patient pathways, including availability of diagnostic and therapeutic services, short-term surgical outcomes and longer-term cancer-specific outcomes”. Colorectal cancer was assessed as a top priority along with breast and gastric cancers [17].
This study focused on COmplete pathological ReSponse rectal CAncer (CORSiCA) and aimed to investigate if nodal metastases independently affected prognosis and the clinical variables correlated with the occurrence of pathologic nodes. In addition, the global variations in the outcomes of rectal cancers presenting a complete pathological response were studied.
Section snippets
Design
This retrospective cohort study was promoted by the European Society of Surgical Oncology (ESSO) Young Alumni Club (EYSAC). The project received approval by ESSO board and was registered on clinicaltrials.gov on November 2017 (ClinicalTrials.gov Identifier: NCT03351959). CORSiCA was publicized using ESSO network and social media and it was officially launched on December 1st, 2017 with a global call closing on March 2017. Actions were also taken by EYSAC steering committee members to spread the
Results
Between December and March 2017, 88 Institutions from all over the world registered in the study, however exclusively 52 of them (59.0%) performed as recruiting centers. About 93% of these 52 institutions were European, whereas non-European centers included Australia, India and Argentina, Fig. 1. Nine Institutions were also enrolled in the pilot investigation [6]. Mean age of the junior investigators was 32.9 ± 4.2 years whereas the seniors were about 15 years older (mean age 48.6 ± 8.9 years);
Discussion
The achievement of a complete pathologic response in the surgical specimen following neoadjuvant treatment is a benchmark of the progress made so far in rectal cancer treatment. Several manuscripts documented the benefits of complete response in terms of survival [6,10] and clinical research is moving forward to explore the benefits of an organ preservation.
This study identified a group of “ugly features” in patients treated with TME; in particular, patients with distal and nodal positive
Funding
None.
Declaration of competing interest
None of the authors has any potential financial conflict of interest related to this manuscript.
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Pathologic stage of ypT0N+ rectal cancers following neo-adjuvant treatment: clinical interpretation of an orphan status
2022, Pathology Research and PracticeCitation Excerpt :Patients with locally advanced non-metastatic rectal cancer usually undergo neoadjuvant treatment prior to surgical resection. Currently, approximately 14–23% of patients achieve a pathologic complete response,[1,2] however, approximately 8% of them still have nodal metastases in the surgical specimen (ypT0N+).[3,4]. Undoubtedly, patients presenting with a complete response have more favorable outcomes than others, but among those responding, the persistence of a nodal disease has been acknowledged as a major risk factor impairing prognosis.[5]
Non-operative Management (NOM) of Rectal Cancer: Literature Review and Translation of Evidence into Practice
2021, Current Colorectal Cancer Reports
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This project was selected for presentation during the Scientific Symposium “Niall O'Higgins Award - Best Abstracts”, during the 38th Congress of the European Society of Surgical Oncology (ESSO 38), held in Budapest October 2018.