Effect of definition of preradiotherapy prostate-specific antigen velocity on its association with prostate cancer-specific mortality and all-cause mortality.

OBJECTIVES: An increasing prostate-specific antigen (PSA) velocity (PSAV) is associated with a shorter time to prostate cancer-specific mortality (PCSM) after definitive local therapy. This study examined the effect on this association when the PSAV was estimated using all PSA values (PSAV-all) instead of the PSA values within 18 months before diagnosis (PSAV-18). METHODS: We studied 358 men (median age 71.2) with clinically localized prostate cancer treated with external beam radiotherapy to a dose of 70.35 Gy from 1989 to 2002. The median follow-up was 4.0 years. The Cox and Gray's multivariate regression analyses were used to evaluate the association between PSAV and the interval to PSA recurrence, all-cause mortality, and PCSM, adjusting for known prognostic factors. RESULTS: The median PSAV-18 and PSAV-all was 1.50 ng/mL/yr (interquartile range 0.74 to 3.82) and 1.20 ng/mL/yr (interquartile range 0.69 to 3.34), respectively. Of the 358 men, 226 (63%) had only two PSA values; therefore, the estimation of their PSAV was the same, irrespective of the method used. Remarkably, despite the identical estimates for PSAV in 63% of the men in this study, after adjusting for known prognostic factors, the hazard ratios describing the significant associations with the interval to PSA recurrence, PCSM, and all-cause mortality increased and the associated P values decreased using PSAV-18 compared with PSAV-all. CONCLUSIONS: The results of this study have shown that the PSAV estimated using the pretreatment PSA values obtained approximately 18 months before diagnosis compared with using all previous PSA values provides a stronger association with the interval to PSA recurrence, PCSM, and all-cause mortality after RT.

Prediagnostic prostate-specific antigen velocity and probability of detecting high-grade prostate cancer.

OBJECTIVES: Men with high-grade prostate cancer experience a survival benefit when androgen suppression therapy is combined with radiotherapy (RT) compared with RT alone. We evaluated whether an association exists between the pretreatment prostate-specific antigen (PSA) velocity and high-grade prostate cancer at diagnosis, controlling for known predictors of high-grade disease. METHODS: The study cohort consisted of 358 men with Stage T1c-T4 prostate cancer treated with external beam RT from 1989 to 2002. Univariate and multivariate logistic regression analyses were used to assess whether an association exists between the pretreatment PSA velocity, PSA level, age, clinical T stage, and Gleason score 4+3 or greater compared with Gleason score 3+4 or less prostate cancer. RESULTS: Of the 358 men, 73 had a Gleason score of 4+3 or greater. The median PSA velocity was 2.71 ng/mL/yr (interquartile range 1.09 to 12.6) for men with a Gleason score of 4+3 or greater and 1.24 ng/mL/yr (interquartile range 0.71 to 3.37) for men with a Gleason score of 3+4 or less. All clinical covariates were significantly associated (P < or = 0.05) with a Gleason score of 4+3 or greater on univariate analysis. On multivariate analysis, the PSA velocity (odds ratio 1.06, 95% confidence interval 1.02 to 1.10, P = 0.004), age (odds ratio 1.07, 95% confidence interval 1.02 to 1.13, P = 0.008), and clinical T stage (odds ratio 2.17, 95% confidence interval 1.21 to 3.92, P = 0.01) were significantly associated with the detection of Gleason score 4+3 or greater prostate cancer. CONCLUSIONS: The prediagnostic PSA velocity, patient age, and clinical T stage were significantly associated with high-grade prostate cancer at diagnosis. Because a biopsy Gleason score of 4+3 or greater is associated with a prostatectomy Gleason score of 7 or greater in the vast majority of cases, these parameters can identify men at high risk of harboring occult high-grade prostate cancer, permitting improved selection of RT fields and the use of androgen suppression therapy.

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.

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.

Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy.

CONTEXT: Men with localized prostate cancer and a preoperative prostate-specific antigen (PSA) velocity greater than 2.0 ng/mL per year experience a 10-fold increase in prostate cancer-specific mortality despite surgery. OBJECTIVE: To assess whether a greater than 2.0-ng/mL increase in PSA level during the year prior to diagnosis was significantly associated with prostate cancer-specific mortality following radiation therapy (RT). DESIGN, SETTING, AND PATIENTS: Between January 1, 1989, and December 1, 2002, 358 men treated with RT for localized prostate cancer formed the study cohort (median age at treatment, 71.2 [range, 43.2-83.5] years). A Cox regression multivariable analysis was used to evaluate whether a PSA velocity greater than 2.0 ng/mL per year was significantly associated with prostate cancer-specific mortality and all-cause mortality after controlling for prognostic factors available at diagnosis. MAIN OUTCOME MEASURE: Time to prostate cancer-specific mortality for the 125 men with low-risk prostate cancer (clinical tumor category T1c or T2a and PSA level <10.0 ng/mL and Gleason score < or =6) and the 233 men with higher-risk disease, stratified by the PSA velocity. RESULTS: A PSA velocity greater than 2.0 ng/mL per year was significantly associated with a shorter time to prostate cancer-specific mortality (adjusted hazard ratio [HR], 12.0; 95% confidence interval [CI], 3.0-54.0; P = .001) and all-cause mortality (adjusted HR, 2.1; 95% CI, 1.3-3.6; P = .005) when compared with men whose PSA velocity was 2.0 ng/mL per year or less. Men presenting with low-risk disease and a PSA velocity greater than 2.0 ng/mL per year had a 7-year estimate of prostate cancer-specific mortality of 19% (95% CI, 2%-39%) compared with 0% for men whose PSA velocity was 2.0 ng/mL per year or less. The corresponding values for men with higher-risk disease were 24% (95% CI, 12%-37%) and 4% (95% CI, 0%-11%), respectively. CONCLUSIONS: A greater than 2.0-ng/mL increase in PSA level during the year prior to diagnosis is associated with a significantly higher risk of death due to prostate cancer following RT despite having low-risk disease. Such men who are planning to undergo RT and are in good health could be considered for RT combined with androgen suppression therapy because this approach improves survival in men with higher-risk disease.