Elsevier

Urology

Volume 76, Issue 4, October 2010, Pages 782-790
Urology

Review Article
Diagnosis of Bone Metastases in Urological Malignancies—An Update

https://doi.org/10.1016/j.urology.2009.12.050Get rights and content

The spread of urological malignancies to bone is a poor prognostic factor. Early detection of metastatic bony lesions assists with tailoring patient management and potentially improving quality of life. Newer therapies such as zolderonic acid for prostate cancer have reinvigorated the importance of clinicians treating bony disease. An array of biochemical and imaging options are available and the order, sensitivity and cost of such investigations need to be understood to maximise clinical benefit. Furthermore, the ideal time to investigate for bony metastases has often been controversial. Although simple history and examination, serum calcium and alkaline phosphatase and plain radiography with bone scintigraphy remain at the forefront of diagnosing bony disease, evolving diagnostic modalities, such as positron emission tomography and newer bone markers need to be considered. The aim of this review is to clarify the role of various investigations and to give clinicians a current analysis of the timing of such investigations in the context of evolving diagnostic modalities and accepted guidelines for urological malignancy.

Section snippets

History and Examination

A physician should be able to determine a level of suspicion of metastatic spread of a malignancy by the clinical assessment of a patient so investigations can be rationalized to answer the clinical question.

History

The main symptom indicating possible bony spread is pain with alternative diagnoses being arthritis, disk prolapse, and musculoskeletal strain or even referred pain.

Pain specific questions that should be elicited are intensity (scale 0-10); location and radiation; onset and character over time; quality; constant or intermittent pain; exacerbating and relieving factors; associated symptoms—especially neurological, eg, pain and altered sensation; impact of patient's daily activities; and current

Examination

During patient examination, signs of cachexia and spinal contour, such as kyphosis, should be reviewed. Observing patient posture and gait can identify possible restriction of movement or pain triggers. To perform this examination, the vertebral column is palpated, with a moderate amount of pressure applied on the individual spinous process to elicit pain. Lateral compression should be applied to spring the rib cage and pelvis. Proximal long bones are also palpated, while asking the patient to

Serum and Bone Markers for Bone Metastases

Bone undergoes regular remodelling via a balance between bone resorption, controlled by osteoclasts, and bone formation governed by osteoblasts. These two processes are tightly coupled together to maintain bone mass. However, metabolic bone diseases including bone metastases alter this balance.

When cancer cells enter into the bone marrow they disrupt normal bone cell turnover by releasing local cytokines and growth factors. This eventually leads to net result of osteolysis or osteosclerosis.

Serum Calcium and Hypercalcemia

Hypercalcemia may produce neurologic, gastrointestinal, renal, and cardiovascular disturbances or even calcification in extraskeletal tissue.11 In some cases, it is a medical emergency requiring hydration, cardiac stabilization, and monitoring. Measuring serum calcium is not routinely conducted as part of urological malignancy assessment with the one exception being in renal cell carcinoma (RCC) where hypercalcemia is more likely related to a paraneoplastic syndrome rather than bone metastases.

Bone Formation

The bone formation markers include the enzyme alkaline phosphatase and by-products of bone matrix synthesis such as osteocalcin and procollagen extension peptides, but these latter two are not yet in clinical practice.10

Bone Resorption

Numerous markers exist using urine and serum tests, including the enzyme tartrate-resistant acid phosphatase (TRAP), products of bone breakdown like calcium and products of bone matrix degradation (eg, hydroxyproline, pyridinium cross-links, telopeptides).14 Again, none is in clinical practice.

Plain Radiography

Plain radiography allows the final result of bone destruction and repair to be seen, predominantly lysis or sclerosis (Table 1). Lytic lesions can be identified through thinning of trabeculae and ill-defined margins that indicate regions of destroyed trabeculae between the central destruction and the radiological normal bone.

Sclerotic lesions are predominately found in CaP; however, they also exist in breast and carcinoid tumors. Radiologically they appear with the following characteristics:

Prostate

The common site for the spread of CaP is bone; it accounts for as much as 80% of all metastases.29 Spread occurs via the hematogenous route to well vascularized areas of the skeleton; red bone marrow of the axial skeleton is the preferred site. CaP cells invade Batson's plexus, which is a low-pressure, high-volume communication venous network between the pelvis and vertebral veins, making the vertebral column the initial site for cancer spread.29

Bone scintigraphy is recommended as the

Conclusions

The detection of bone metastases in patients with urological malignancies will alter the treatment plan. It allows for appropriate measures to be taken to prevent complications and improve quality of life. The use of clinical suspicion, bone markers, radiological imaging, and histologic sampling increases the yield of detecting metastatic spread. The use of these investigations depends on many factors such as accuracy, timing, cost-effectiveness, and availability. Current recommendations based

Acknowledgments

We would like to acknowledge the Nuclear Medicine Department and the Centre for PET at Austin Hospital, Melbourne, Australia for providing the images; and Alan Wong from the Austin Department of Pathology for assisting with photographing the histology slides.

References (50)

  • E. Seaman et al.

    Association of radionuclide bone scan and serum alkaline phosphatase in patients with metastatic renal cell carcinoma

    Urology

    (1996)
  • D.E. Kang et al.

    Clinical use of fluorodeoxyglucose F-18 positron emission tomography for detection of renal cell carcinoma

    J Urol

    (2004)
  • P. Davey et al.

    Bladder cancer: the value of routine bone scintigraphy

    Clin Radiol

    (1985)
  • A. Lindner et al.

    Cost-effective analysis of pre-cystectomy radioisotope scans

    J Urol

    (1982)
  • C.S. Ng

    Radiologic diagnosis and staging of renal and bladder cancer

    Semin Roentgenol

    (2006)
  • G.D. Roodman

    Mechanisms of bone metastasis

    N Engl J Med

    (2004)
  • H.L. Abrams et al.

    Metastases in carcinoma; analysis of 1000 autopsied cases

    Cancer

    (1950)
  • D.I. Rosenthal

    Radiologic diagnosis of bone metastases

    Cancer

    (1997)
  • A. Jemal et al.

    Cancer statistics, 2007

    CA Cancer J Clin

    (2007)
  • G.R. Mundy

    Metastasis to bone: causes, consequences and therapeutic opportunities

    Nat Rev Cancer

    (2002)
  • V. Vassiliou et al.

    The management of metastatic bone disease with the combination of bisphosphonates and radiotherapy: from theory to clinical practice

    Curr Med Chem Anti Cancer Agents

    (2009)
  • Saad F, Eastham J, McKiernan J and Congress. PatXEAoU: Long-term reduction of bone pain and skeletal morbidity with...
  • A. Fontana et al.

    Markers of bone turnover in bone metastases

    Cancer

    (2000)
  • R.A. Schaiff et al.

    Medical treatment of hypercalcemia

    Clin Pharmacol

    (1989)
  • R. Vassilopoulou-Sellin et al.

    Incidence of hypercalcemia in patients with malignancy referred to a comprehensive cancer center

    Cancer

    (1993)
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