Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study.

OBJECTIVE: To define the optimum tamoxifen dose for reducing bicalutamide (CASODEX) 150 mg monotherapy-induced breast events (ie, gynaecomastia or breast pain or both) without compromising disease control. METHODS: This was a double-blind, parallel-group, multicentre trial in which 282 patients with prostate cancer were randomised to receive bicalutamide 150 mg/d plus either daily tamoxifen (1, 2.5, 5, 10, or 20mg) or placebo for 12 mo, followed by 12 mo of treatment with bicalutamide only. Primary end points were incidence of breast events and prostate-specific antigen (PSA) inhibition and were analysed at 6 mo (the primary analysis) and also at 12 and 24 mo. RESULTS: At 6 and 12 mo, tamoxifen decreased the incidence of breast events in a dose-dependent manner, with breast events observed in 86.2%, 60.0%, 55.3%, 23.5%, and 8.8% of patients receiving tamoxifen 1, 2.5, 5, 10, and 20 mg, respectively, compared with 96.7% of patients receiving placebo at 6 mo. At 24 mo (ie, after 12 mo of bicalutamide monotherapy), a high incidence of breast events was seen in all groups. There was no evidence of a negative effect on PSA inhibition at any assessment. Other nonbreast adverse effects were similar across groups, except for an increase in hot flushes with tamoxifen doses > or =5 mg. CONCLUSION: These findings suggest that prophylactic tamoxifen 20 mg/d is an effective dose for reduction of bicalutamide-induced breast events and does not appear to affect disease control based on PSA suppression.

Value of repeat ultrasonic prostatic biopsies following negative digitally directed biopsy.

OBJECTIVE: The objective of this study was to determine the benefit of repeat transrectal ultrasound-guided prostatic biopsy (TRUSBx) among men with prior benign histology on digitally guided biopsy despite suspicious digital rectal examination (DRE) findings. PATIENTS AND METHODS: From January 1, 1990 to May 30, 1993, we evaluated 130 consecutive men, referred to us with benign pathology on digitally-guided biopsy and DRE suspicious of cancer. All patients underwent systematic and directed TRUSBx. RESULTS: TRUSBx detected previously undiagnosed malignancy in 67 cases (51%). CONCLUSION: It is mandatory to reevaluate by TRUSBx, all patients with a palpable abnormality on DRE and a prior benign pathology on digitally-guided biopsy, as the likelihood of finding cancer is elevated.

Analysis of gland volume effect on the performance of PSA density in early detection of non-palpable, isoechoic prostate cancer.

OBJECTIVE: To reassess PSA density (PSAD) in the detection of non-palpable, isoechoic prostate cancer and to analyze the effect of potentially inaccurate non-planimetric transrectal ultrasound volume estimates on the diagnostic performance of this diagnostic tool. METHODS: We prospectively evaluated 343 consecutive men with non-suspicious digital rectal examination and transrectal ultrasound findings and with serum PSA in the intermediate range (4.1-10 ng/mL). All men underwent systematic sextant biopsies of the peripheral zone. We performed a two-fold analysis of PSAD performance first using measured gland volume and then using modified gland volumes ranging from a 25% underestimation to a 25% overestimation, in 5% stepwise increments. RESULTS: With a 0.15 PSAD cut-off, we would have missed 14, 34 and 48% of cancers, if we had respectively used a volume underestimate of 25%, the measured volume and a volume overestimate of 25%. CONCLUSIONS: Potential gland volume under- or overestimation may substantially affect the diagnostic performance of PSAD. Although PSAD may represent a useful adjunct in the early detection of prostate cancer, it may compromise cancer detection in a substantial proportion of cases, if used as the only indicator for biopsy.