The introduction of an effective blood test, prostate specific antigen (PSA), has made it possible to diagnose more and more men in an earlier stage where they can be offered potentially curative treatments. The other side of the coin is that if effective diagnostic procedures are used unselectively in elderly men with a short life expectancy, a problem with over diagnosis and over treatment might occur. Thus the same stage of prostate cancer may need different treatment strategies, pending on the patient’s life expectancy. This, and many other issues regarding the disease, is the subject of the EAU guidelines on prostate cancer. G UI DE LI N ES O N P RO ST AT E CA N CE R 10

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Guidelines on Prostate Cancer

I Introduction II Normal Calcium and Bone Homeostasis A Bone remodeling B Calcium homeostasis C Defenses against hyper- and hypocalcemia III Humoral Mechanisms by Which Solid Tumors Affect the Skeleton A Hypercalcemia B Oncogenic osteomalacia C Tumor lysis syndrome IV Local Mechanisms by Which Tumors Affect the Skeleton A Clinical manifestations B Pathophysiology of the metastatic process to bone C Local tumor syndromes in bone D Therapy of tumor in bone

Cancer and bone

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (α CTX) and β isomerized (β CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P< 0.006–0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary α CTX, 149% for urinary β CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary α CTX, urinary β CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients. © 2000 Cancer Research Campaign

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Markers of bone turnover for the management of patients with bone metastases from prostate cancer

A Phase III Extension Trial With a 1-Arm Crossover From Leuprolide to Degarelix: Comparison of Gonadotropin-Releasing Hormone Agonist and Antagonist Effect on Prostate Cancer

The aim of this study was to analyse the clinical utility of serum bone alkaline phosphatase (BAP) in addition to prostate-specific antigen (PSA) in the staging of newly diagnosed untreated prostate cancer patients. A prospective study was conducted, analysing serum BAP and PSA concentrations in 295 consecutive newly diagnosed untreated prostate cancer patients (T1–4, N0–1, M0–1b), 93 of whom had bone metastases on bone scan. The relationship of each marker with extent of bone disease, the influence of several clinical variables on both serum marker levels, the efficiency in predicting bone metastasis through receiver operating characteristic curves and, finally, the clinical utility in avoiding unnecessary bone scans were determined. Significant differences were found in the serum levels of both BAP and PSA between patients with and patients without bone metastases. Multiple regression analysis showed the extent of bone disease to be the only variable that influenced both serum levels. However, while serum BAP levels showed a statistical relationship with extent of bone disease, serum PSA levels did not. The best prediction of bone scan findings was obtained with the combination of both markers using a cut-off of 20 ng/ml, with positive and negative predictive values of 46.5% and 100%, respectively. This greater efficiency could permit 32.2% of initial bone scans to be avoided. False-positive and false-negative rates of BAP were 7.5% and 14%, respectively. This study suggests that serum BAP levels could play a complementary role in the diagnosis of bone metastasis in prostate cancer patients. This marker could provide useful clinical information on the degree of skeletal metastasis and constitute an easy way of enhancing the clinical utility of PSA. The addition of this marker to PSA in the initial evaluation could permit staging bone scan to be avoided at a PSA range of 10–20 ng/ml, with significant implications for cost saving.

Serum bone alkaline phosphatase levels enhance the clinical utility of prostate specific antigen in the staging of newly diagnosed prostate cancer patients.

H. Valenzuela

Papers

Clinical Efficacy of Bone Alkaline Phosphatase and Prostate Specific Antigen in the Diagnosis of Bone Metastasis in Prostate Cancer