Toward the optimal use of androgen suppression therapy in the radiotherapeutic management of prostate cancer.
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Androgen Antagonists↗
Biomedical subjects
Anthony V D'Amico
Publications and source records attributed to Anthony V D'Amico.
Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.
PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.
Humans↗
Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial.
BACKGROUND: Use of 5 mg/day finasteride (Proscar) for benign prostatic hyperplasia is known to affect serum concentrations of prostate-specific antigen (PSA). When men taking this treatment undergo screening for prostate cancer, a compensatory adjustment of the PSA concentration (to multiply the value by two) is recommended. Whether this recommendation should apply to men taking 1 mg/day finasteride (Propecia) for the treatment of androgenic alopecia is unknown. We aimed to assess the effect of 1 mg/day finasteride on serum PSA in men aged 40-60 years with male-pattern hair loss. METHODS: Between March 13, 1998, and Jan 12, 2000, 355 men aged 40-60 years with male-pattern hair loss were stratified by age decade (40-49 years and 50-60 years), and randomised in a ratio of four to one to 1 mg/day finasteride or placebo. The primary endpoint was the effect of this treatment for 48 weeks on serum PSA concentration compared with placebo. This trial is in the process of being registered on the US National Institutes of Health website . Analyses were according to protocol. FINDINGS: Within 48 weeks of randomisation, men aged 40-49 years and 50-60 years who were assigned 1 mg/day finasteride had a median decrease in serum PSA concentration of 40% (95% CI 34-46) and 50% (44-57), respectively. In men assigned placebo, the median changes were 0% [-14 to 14] and a median increase of 13% [2 to 24], respectively. INTERPRETATION: In men aged 40-60 years, 1 mg/day finasteride for 48 weeks lowers serum PSA concentration. Therefore, the existing recommendation for the adjustment of serum PSA concentration in prostate-cancer screening in men taking 5 mg/day finasteride should also apply to men taking the 1 mg/day preparation for male-pattern hair loss. Research is needed to assess the effect of 1 mg/day finasteride preparation beyond 48 weeks of treatment.
5-alpha Reductase Inhibitors↗
Cancer-specific mortality after radiation therapy with short-course hormonal therapy or radical prostatectomy in men with localized, intermediate-risk to high-risk prostate cancer.
BACKGROUND: The presence of multiple determinants of aggressive cancer biology may impact prostate cancer-specific mortality (PCSM) rates compared with fewer factors. The authors estimated PCSM after radiation therapy with short-course androgen suppression therapy (RT+AST) or radical prostatectomy (RP) in men with clinically localized, intermediate-risk to high-risk prostate cancer. METHODS: The study cohort included 3240 men treated from 1981 to 2002 with RT with 6 months of AST (n = 550) or RP (n = 2690) for localized prostate cancer with at least 1 risk factor (prostate-specific antigen [PSA] >10 ng/mL, biopsy Gleason score 7-10, or clinical tumor category T2b or T2c). Competing risks regression analyses were used to determine whether the number of risk factors present was associated with time to PCSM. RESULTS: Men with all 3 risk factors had significantly shorter time to PCSM after RT+AST (adjusted hazards ratio [HR] of 9.3; 95% confidence interval [95% CI], 1.9-44.5 [P(Gray) = .005]) or RP (adjusted HR of 6.3; 95% CI, 3.2-12.2 [P(Gray) < .001]) when compared with men with any 1 or 2 risk factors. The 7-year estimates of PCSM for men having 1, 2, or 3 risk factors were 0.83% (95% CI, 0.27-1.4%), 2.6% (95% CI, 1.0-4.2%), and 12.6% (95% CI, 7.1-18.1%), respectively. CONCLUSIONS: Men with multiple determinants of intermediate-risk to high-risk prostate cancer have significantly increased estimates of PCSM despite aggressive therapy compared with men with only 1 or 2 determinants. These men are appropriate candidates for enrollment onto randomized controlled trials evaluating the benefit of adding systemic therapies such as docetaxel to RT+AST or RP.
Aged↗
Patient and treatment factors associated with complications after prostate brachytherapy.
PURPOSE: To assess the prevalence and predictors of complications after prostate brachytherapy in a population-based sample of older men. PATIENTS AND METHODS: We analyzed claims for Medicare-enrolled men older than age 65 years living in Surveillance, Epidemiology, and End Results (SEER) surveillance areas diagnosed with prostate cancer from 1991 to 1999 who underwent brachytherapy as initial treatment. RESULTS: There were 5,621 men who had brachytherapy with at least 2 years of follow-up. A complication diagnosis or invasive procedure occurred in 54.5% of men within 2 years, with 14.1% undergoing an invasive procedure. Urinary, bowel, and erectile morbidity rates were 33.8%, 21.0%, and 16.7%, respectively, and invasive procedure rates were 10.3%, 0.8%, and 4.0%, respectively. On multivariable analysis, combined urinary diagnoses and invasive procedures (obstruction, incontinence, bleeding, fistula) were associated with older age (P < .01), nonwhite race (odds ratio [OR], 1.30; P = .01), low income (OR, 1.74; P < .01), external-beam radiotherapy (EBRT; OR, 0.85; P = .01), androgen deprivation (OR, 1.31; P < .01), later year of brachytherapy (OR, 1.03/yr; P = .02), higher Charlson comorbidity score (P < .01), and prior transurethral resection of the prostate (OR, 1.65; P < .01). Bowel morbidity (bleeding/proctitis, injury) was associated with older age (P = .04), EBRT (OR, 1.46; P < .01), later year (OR, 1.04/yr; P < .01), higher Charlson score (P = .01), and inflammatory bowel disease (OR, 2.60; P < .01). Erectile morbidity was associated with younger age (P < .01), nonwhite race (OR, 1.37; P < .01), AD (OR, 1.18; P = .04), and later year (OR, 1.08/yr; P < .01). Invasive procedure rates declined with later year of brachytherapy (OR, 0.93/yr; P < .01). CONCLUSION: Morbidity after prostate brachytherapy was common, though invasive procedures were required infrequently. Invasive procedures for complications declined during the 1990s, suggesting technical improvement with experience.
Aged↗
Prostate-specific antigen recurrence and mortality after conventional dose radiation therapy in select men with low-risk prostate cancer.
BACKGROUND: Prostate-specific antigen (PSA) recurrence, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) were evaluated for men age >70 years receiving conventional dose external beam radiation therapy (RT). METHODS: Between January 1, 1989, and December 1, 2002, 358 men were treated with RT for localized prostate cancer at a Harvard Medical School Affiliate in Fall River, MA. Median age was 71.2 (range, 43.2-83.5) years and patients were followed for a median of 4.0 (range, 0.2-13.5) years. RESULTS: Univariable analysis demonstrated that increasing pretreatment PSA velocity was significantly associated with increasing pretreatment PSA (P < .0001), Gleason score (P = .0002), and shorter post-RT PSA doubling time (P = .0007) but not with clinical T-category (P = .09) or percent positive biopsies (P = .08). For the select cohort of men age >70 years with low-risk disease and a pretreatment PSA velocity < or =1.0 ng/mL per year, all deaths observed to date have been from nonprostate cancer etiologies. Whereas PSA recurrence in this group reached 43.3% by 7 years, due to the advanced age of the cohort and less aggressive biology, competing causes of mortality predominated as the cause of death despite PSA failure. CONCLUSIONS: In men age >70 years with low-risk prostate cancer and pretreatment PSA velocity < or =1.0 ng/mL/year, prostate cancer death was not observed despite a modest PSA recurrence rate.
Adult↗
Motion and shape change when using an endorectal balloon during prostate radiation therapy.
PURPOSE: To investigate motion and shape change when using an endorectal balloon (ERB) in patients receiving radiotherapy for prostate cancer. METHODS: In nine patients treated for prostate cancer using an ERB, the anterior wall of the ERB was contoured on right lateral images taken immediately before irradiation, and on left lateral images taken immediately after irradiation. Changes in the contours were used to calculate inter-fraction shape change and inter-imaging motion and shape change. Inter-imaging motion describes changes that occur after the right lateral image is taken that are seen in the left lateral image. RESULTS: Eighty-six percent of all inter-imaging shifts of the anterior wall of the ERB were in the posterior direction (mean: 1.8 mm, 1 SD: 1.8 mm, maximum posterior shift: 2.8-7.2 mm). The inter-fraction shape change (1 SD) of the anterior wall was equivalent to a change in the angle of the balloon of 2.5-5.7 degrees, with a range of 8-20 degrees, depending on the patient. Inter-imaging shape changes were similar in size. CONCLUSIONS: The inter-imaging motion and shape changes may be explained by the patient relaxing some time after insertion of the ERB, indicating that it could be reduced by a waiting period after insertion before irradiation. Development of image-guided localization strategies should consider intra-fraction motion and also inter- and intra-fraction shape change.
Catheterization↗
Six-month androgen suppression plus radiation therapy compared with radiation therapy alone for men with prostate cancer and a rapidly increasing pretreatment prostate-specific antigen level.
PURPOSE: We evaluated whether treatment with 6 months of androgen-suppression therapy (AST) and radiation therapy (RT) compared with RT was associated with the time to prostate-specific antigen (PSA) recurrence, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) in men with a pretreatment PSA velocity more than 2 ng/mL/yr. PATIENTS AND METHODS: The study cohort comprised 241 men with clinically localized or locally advanced prostate cancer treated with RT and AST or RT from 1989 to 2002. Cox regression and Gray's formulation were used to assess whether treatment was associated significantly with the time to PSA recurrence or ACM and PCSM, respectively, adjusting for known prognostic factors. RESULTS: Despite the significantly longer median follow-up, younger age at diagnosis, higher proportion of Gleason score 7 to 10, and advanced T-category cancers, significantly lower estimates of PSA recurrence (P < .001), PCSM (P = .007), and ACM (P < .001) were observed in men who were treated using RT and AST compared with RT. Treatment with RT and AST compared with RT was associated with a longer time to PSA recurrence (adjusted hazard ratio [HR], 0.22; 95% CI, 0.14 to 0.35; P < .001), PCSM (HR, 0.23, 95% CI, 0.09 to 0.64; P = .005), and ACM (HR, 0.30; 95% CI, 0.16 to 0.58; P < .001). CONCLUSION: Treatment using 6 months of AST and RT compared with RT in men with a pretreatment PSA velocity greater than 2 ng/mL/yr was associated with a longer time to PSA recurrence, PCSM, and ACM.
Aged↗
Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer.
BACKGROUND: The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer-specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate-specific antigen (PSA) levels after they received local treatment. METHODS: The study population consisted of 67 patients who had a PSA doubling time (DT) < or =6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS: : A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score > or =8 (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8% versus 50.9% for patients with a PSA nadir < or =0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score < or =7 versus > or =8, respectively. CONCLUSIONS: : Among men with a PSA DT < or =6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score > or =8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer.
Aged↗
Perineural invasion associated with increased cancer-specific mortality after external beam radiation therapy for men with low- and intermediate-risk prostate cancer.
PURPOSE: To identify an association between perineural invasion (PNI) and cancer-specific survival in patients with prostate cancer after standard-dose external beam radiation therapy (RT). METHODS AND MATERIALS: A total of 517 consecutive patients who underwent RT (median dose, 70.5 Gy) between 1989 and 2003 for low-risk or intermediate-risk prostate cancer were studied. A genitourinary pathologist (AAR) scored presence or absence of PNI on all prostate needle-biopsy specimens. A Cox regression multivariable analysis was performed to assess whether the presence of PNI was associated with risk of prostate cancer-specific mortality after RT when the recognized risk-group variables were factored into the model. Estimates of cancer-specific mortality were made using a cumulative incidence method. Comparisons of survival were made using a two-tailed log-rank test. RESULTS: At a median follow-up of 4.5 years, 84 patients (16%) have died, 15 of 84 (18%) from prostate cancer. PNI was the only significant predictor of prostate cancer-specific mortality after RT (p=0.012). The estimated prostate cancer-specific mortality was 14% at 8 years for PNI+ patients vs. 5% for PNI- patients (p=0.0008). CONCLUSIONS: Patients with low- or intermediate-risk prostate cancer who have PNI on prostate needle biopsy have a significantly higher rate of prostate cancer-specific mortality after standard-dose radiation therapy than patients without PNI. Although this analysis is retrospective, this association argues for consideration of the use of more aggressive therapy, such as hormonal therapy with RT or dose escalation, in these select patients.
Biopsy, Needle↗
Predictors of mortality after prostate-specific antigen failure.
PURPOSE: We identified factors associated with the length of survival after prostate-specific antigen (PSA) failure. METHODS AND MATERIALS: The study cohort comprised 81 of 206 men enrolled on a randomized trial evaluating external-beam radiation therapy (RT) with or without androgen suppression therapy (AST) and who experienced PSA failure. Salvage AST was administered at a PSA level of approximately 10 ng/mL as per protocol. Cox regression was used to determine factors associated with length of survival after PSA failure. RESULTS: A PSA DT (doubling time) <6 months (p = 0.04) and age at the time of PSA failure (p = 0.009) were significantly associated with length of survival. By 5 years, 35% and 65% of all-cause mortality was from prostate cancer in men whose age at PSA failure was 75 or higher vs. <75, respectively. Across all ages, 0%, 4%, as compared with 63% of men, were estimated to die of prostate cancer within 5 years after PSA failure if their PSA DT was >12, 6-12, or <6 months, respectively. CONCLUSIONS: Advanced age and a PSA DT <6 months at the time of PSA failure are associated with a significantly shorter survival.
Aged↗
A prospective evaluation of rectal bleeding after dose-escalated three-dimensional conformal radiation therapy using an intrarectal balloon for prostate gland localization and immobilization.
OBJECTIVES: To estimate the rates of rectal bleeding after dose-escalated three-dimensional conformal radiation therapy (3D-CRT) on a prospective, Phase II study in which a modified intrarectal balloon was used for prostate gland localization and immobilization. METHODS: The study cohort comprised 100 men with biopsy-proven adenocarcinoma of the prostate and at least one high-risk feature (prostate-specific antigen level greater than 10 ng/mL, Gleason score 7 or higher, or clinical or radiographic T3 disease). Treatment consisted of androgen suppression therapy and four-field 3D-CRT with an intrarectal balloon for the initial 15 treatments. Planning treatment volume dose was 75.6 Gy. The primary endpoint of time to grade 3 rectal bleeding was estimated with the Kaplan-Meier method for 57 men with a minimum follow-up of 1 year. RESULTS: For 57 men with a median (range) follow-up of 1.8 (1.0 to 3.3) years, the median (range) volume of rectum exceeding 70 Gy was 3.7 (0.6 to 14.7) cm3, and the 2-year estimate of grade 3 rectal bleeding rate was 10%. This rate was 100% as compared with 0 (P < 0.0001) for men who were taking warfarin (n = 3) or high-dose aspirin (n = 1) as compared with neither, respectively. All grade 3 rectal bleeding events were controlled with argon plasma coagulation. CONCLUSIONS: Dose-escalated 3D-CRT with an intrarectal balloon technique for prostate localization and immobilization produced no measurable grade 3 rectal bleeding unless the patient was taking anticoagulants.
Adenocarcinoma↗
Impact of age, benign prostatic hyperplasia, and cancer on prostate-specific antigen level.
BACKGROUND: The distribution of prostate-specific antigen (PSA) values for men with or without prostate carcinoma are confounded because of verification bias. Correcting for verification bias, the means and variances of PSA values were estimated in specific clinical scenarios. METHODS: Existing receiver operating characteristic (ROC) curves, adjusted for the presence of verification bias in a screening population, were used to estimate the mean and variance of PSA values for men with or without prostate carcinoma, stratified by age and the presence or absence of benign prostatic hyperplasia. Men with a suspicious digital rectal exam (nodular) were excluded from analysis. RESULTS: Among men with cancer and the absence of benign prostatic hyperplasia, mean PSA values were 2.05 ng/mL and 2.66 ng/mL for younger (<60 yr) and older (> or =60 yrs) men, respectively. These estimates were 2.56 ng/mL and 3.90 ng/mL in the presence of benign prostatic hyperplasia for younger and older men, respectively. For men without prostate carcinoma, these values were 0.78 ng/mL and 1.23 ng/mL for younger and older men, respectively, among those without benign prostatic hyperplasia, and 0.97 ng/mL and 1.75 ng/mL for younger and older men, respectively, among those with benign prostatic hyperplasia. CONCLUSIONS: Accurate estimates of the mean and variance of PSA values for men with or without cancer may provide PSA thresholds for biopsy that are specific for age and prostate size as assessed by digital rectal exam. Therefore, the current threshold of 4.0 ng/mL should not be applied indiscriminately.
Age Factors↗
Prostate-specific antigen velocity and survival for patients with hormone-refractory metastatic prostate carcinoma.
BACKGROUND: The authors investigated whether prostate-specific antigen (PSA) velocity was associated significantly with the time to death after randomization among patients with hormone-refractory metastatic prostate carcinoma (HRMPC) who were treated with cytotoxic, cytotatic, or combination therapy. METHODS: The study cohort included 213 men with HRMPC who were treated on 3 prospective, randomized Phase II studies between February 1996 and October 2001. Cox regression analysis was used to evaluate whether there was a significant association between PSA velocity and the time to death after randomization, controlling for treatment and known prognostic factors. RESULTS: Increasing PSA velocity was associated significantly with shorter survival after randomization (P = 0.005) controlling for treatment and known prognostic factors. The adjusted hazard ratio for death was 1.8 (95% confidence interval [95% CI], 1.3-2.5; P = 0.0004) for men who had a PSA velocity > 0.0 ng/mL per month compared with men who had a PSA velocity < or = 0.0 ng/mL per month. Estimates of survival 2 years after randomization for these men were 16% (95% CI, 7-25%) and 44% (95% CI, 35-53%), respectively. CONCLUSIONS: PSA velocity was associated significantly with the length of survival among men with HRMPC who received cytotoxic, cytostatic, or combination therapy.
Adult↗
Identifying men diagnosed with clinically localized prostate cancer who are at high risk for death from prostate cancer.
PURPOSE: We identified factors at diagnosis that are significantly associated with time to prostate cancer specific mortality following radical prostatectomy or external beam radiation therapy. MATERIALS AND METHODS: The study cohort included 1,453 men treated with radical prostatectomy (1,095) or external beam radiation therapy (358) for localized prostate cancer between 1989 and 2002. Cox regression multivariate analysis was used to evaluate whether prostate specific antigen, prostate specific antigen velocity, biopsy Gleason score and clinical tumor category at diagnosis were significantly associated with time to prostate cancer specific mortality following radical prostatectomy or external beam radiation therapy. RESULTS: In addition to increasing prostate specific antigen (p < or =0.04) and biopsy Gleason score 8 to 10 disease (p < or =0.02), prostate specific antigen velocity more than 2 ng/ml yearly was significantly associated with shorter time to prostate cancer specific mortality in patients treated with radical prostatectomy (adjusted HR 12, 95% CI 3 to 54) and external beam radiation therapy (adjusted HR 12, 95% CI 3 to 54) compared with that in men with prostate specific antigen velocity 2 ng/ml yearly or less (p < or =0.001). Despite low risk disease 7-year estimates of prostate cancer specific mortality were 5% to 19% in patients in whom prostate specific antigen increased by more than 2 ng/ml during the year before diagnosis compared with less than 1% in those with a prostate specific antigen increase of 2 ng/ml or less. CONCLUSIONS: Despite prostate specific antigen level less than 10 ng/ml and Gleason score 6 cancer a prostate specific antigen increase of more than 2 ng/ml during the year before diagnosis places a man at high risk for prostate cancer death following radical prostatectomy or external beam radiation therapy.
Aged↗
Prostate cancer prevention and finasteride.
PURPOSE: We assessed whether the association between the larger changes in prostate specific antigen and high grade prostate cancer observed in the Prostate Cancer Prevention Trial can explain the increased detection of high grade prostate cancer in men randomized to finasteride vs placebo. MATERIALS AND METHODS: A literature review was performed to obtain evidence to develop a hypothesis that may explain the results of the Prostate Cancer Prevention Trial. RESULTS: On average finasteride halved prostate specific antigen. As shown by the Medical Therapy of Prostatic Symptoms study and Prostate Cancer Prevention Trial, it also decreased the annual median increase in prostate specific antigen from benign prostatic hyperplasia. Therefore, despite doubling prostate specific antigen during the first 3 years of the Prostate Cancer Prevention Trial, to have prostate specific antigen exceed 4 ng/ml and have a prostate biopsy recommended men receiving finasteride vs placebo required greater increases in prostate specific antigen, which was shown in the Prostate Cancer Prevention Trial to be associated with high grade disease (p < 0.001). Also, the decrease of the contribution to prostate specific antigen from benign prostatic hyperplasia by finasteride improved the performance characteristics of prostate specific antigen to detect Gleason score 7 or higher prostate cancer. CONCLUSIONS: By decreasing the contribution to prostate specific antigen from benign prostatic hyperplasia finasteride makes changes in prostate specific antigen more cancer specific. This effect may explain the increased detection of high grade prostate cancer in men randomized to finasteride in the Prostate Cancer Prevention Trial. How to best use prostate specific antigen to recommend biopsy in men on 5alpha-reductase inhibitors requires further study.
Enzyme Inhibitors↗
Radical prostatectomy for high-grade prostate cancer.
OBJECTIVES: Patients with high-grade clinically localized disease often have disease beyond the prostate and, if so, are unlikely to benefit from radical prostatectomy in the long-term. The objective of this study was to assess whether use of other known prognostic factors could be helpful in defining which men with Gleason 8 to 10 prostate cancer are most likely to benefit from surgical management. METHODS: A retrospective analysis was performed on men with biopsy Gleason 8 to 10 prostate cancer who underwent radical prostatectomy at two major university centers. No patients received hormonal therapy as part of initial treatment or adjuvant radiation therapy. Surgery was performed using a retropubic approach, and lymph node dissection was performed in all patients. Risk groups were defined based on prostate-specific antigen (PSA) value and percent positive biopsy cores (%PBC). A Cox proportional hazards analysis was performed to assess for differences in pretreatment prognostic factors. Kaplan-Meier curves were generated for each group, and then comparisons between groups were performed using log-rank analysis to assess for differences in 5-year actuarial freedom from biochemical failure. RESULTS: Radical prostatectomy was performed on 196 patients between 1987 and 2002, of whom 168 had sufficient data for analysis. Median follow-up was 18 months (range, 1 to 130 months), with 31 patients at risk for more than 5 years. Patients with a PSA value of less than 10 ng/mL and %PBC of less than 50% had a 5-year actuarial biochemical control rate of 67% versus 23% for all other patients (P = 0.0001). CONCLUSIONS: PSA value and %PBC are useful in selecting patients with high-grade prostate cancer most likely to benefit by radical prostatectomy.
Follow-Up Studies↗
Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality.
OBJECTIVES: To compare the preoperative characteristics, postoperative prostate-specific antigen (PSA) doubling time (DT), and prostate cancer-specific mortality (PCSM) estimates after PSA failure in men diagnosed during a screening study versus a community referral population. A PSA-DT of less than 3 months is a surrogate endpoint for PCSM. METHODS: From 1988 to 2002, 1492 of 9637 patients with clinically localized prostate cancer underwent radical prostatectomy and experienced PSA failure. They were either participating in a screening study (n = 841) or attended 1 of 44 community-based practices (n = 611). The distributions of PSA, Gleason score, tumor stage, and PSA-DT were compared using chi-square metric. The estimates of PCSM after PSA failure were compared using Gray's P value. RESULTS: Compared with the community population, the annually screened men experiencing PSA failure had a lower PSA level at diagnosis (5.1 versus 9.5 ng/mL, P <0.0001), were less likely to have Gleason score 7 to 10 cancer (25.1% versus 42.1%, P <0.0001), and were more likely to have low-risk disease (64.5% versus 23.8%, P <0.0001). Furthermore, the screened cohort had a reduction (P <0.0001) in the proportion with a PSA-DT of less than 3, 3 to 5.99, and 6 to 11.99 months and a significant increase in the proportion with a PSA-DT of 12 months or longer. After a median follow-up of 4.5 and 4.1 years after PSA failure in the screened and community cohorts, respectively, the PCSM estimates were lower (P = 0.0002) in the screened cohort (10-year estimate 3.6% [95% confidence interval 1.3 to 5.8] versus 11.3% [95% confidence interval 5.9 to 17.4]). CONCLUSIONS: Patients diagnosed by annual prostate cancer screening appeared more likely to experience an indolent PSA recurrence and less likely to die of prostate cancer after PSA recurrence compared with patients referred from the community.
Adult↗