Marie E. Vastola

Low rates of androgen deprivation therapy use with salvage radiation therapy in patients with prostate cancer after radical prostatectomy

OBJECTIVE The RTOG 9601 and GETUG-AFU 16 randomized controlled trials demonstrated that the addition of androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) improves progression-free and, for RTOG 9601, overall survival. We examined national trends in the use of ADT with SRT. MATERIALS AND METHODS Of the 484,009 patients in the National Cancer Database from 2004 to 2012 with localized or locally advanced prostate cancer treated with radical prostatectomy (RP), 4,200 men received SRT (≥6mo after surgery). We used Pearsons chi-squared test to evaluate changes in ADT use, and multiple logistic regression to examine predictors of ADT use. RESULTS Overall, 32.1% of SRT patients received ADT, which increased after initial results of RTOG 9601 showed an improvement in metastasis-free survival in 2010 (28.5% in 2008/2009 vs. 34.5% in 2011/2012, P = 0.006). Predictors of ADT use include presurgery prostate-specific antigen>20ng/ml vs.<10ng/ml (adjusted odds ratio [AOR] = 1.34, P = 0.002; 36.7% vs. 29.6%); positive vs. negative margins (AOR = 1.29, P = 0.001; 34.9% vs. 27.8%); Gleason 3+4 (AOR = 1.53; 21.3%), Gleason 4+3 (AOR = 2.40; 32.0%), or Gleason 8 to 10 (AOR = 4.49; 49.2%) vs. Gleason 2 to 6 (P≤0.005 for all; 13.2%); and pathologic T3a (AOR = 1.46; 30.9%), T3b (AOR = 2.50; 47.6%), or T4 (AOR = 4.14; 60.9%) vs. T2 (P<0.001 for all; 19.1%). Starting SRT 12 to 23.9 months (AOR = 0.69; 23.2%) or≥24 months (AOR = 0.25; 8.0%) after RP was associated with decreased odds of ADT use vs. starting SRT 6 to 8.9 months after RP (P≤0.002 for both; 35.0%). CONCLUSION Although less than one-third of SRT patients from the study era received ADT, there is evidence that physicians and patients have begun slowly adopting this practice with the 2010 reporting of a decrease in the cumulative incidence of metastases with the addition of ADT to SRT. Given the newly reported survival benefit of RTOG 9601, additional work will be necessary to identify which patients benefit the most from the use of ADT with SRT to individualize treatment.

Pathologic Outcomes of Gleason 6 Favorable Intermediate-Risk Prostate Cancer Treated With Radical Prostatectomy: Implications for Active Surveillance

&NA; We examined the pathologic outcomes of 2807 men with Gleason 6 favorable intermediate‐risk (FIR) prostate cancer treated with radical prostatectomy; 25.5% of patients with prostate‐specific antigen of 10 to 20 ng/mL and 12.4% with cT2b to T2c stage harbored higher grade or stage disease, suggesting that Gleason 6 FIR patients with cT2b to T2c tumors might generally be reasonable candidates for active surveillance. Background: The safety of active surveillance (AS) for Gleason 6 favorable intermediate‐risk (FIR) prostate cancer is unknown. To provide guidance, we examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR patients treated with radical prostatectomy. Patients and Methods: We identified 2807 men in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 6 FIR disease (<50% positive biopsy cores [PBC] with either prostate‐specific antigen [PSA] of 10‐20 ng/mL or cT2b‐T2c disease) treated with radical prostatectomy. Logistic regression was used to identify predictors of upgrading (Gleason 3+4 with tertiary Gleason 5 or Gleason ≥4+3) or upstaging (pT3‐4/N1). Results: Fifty‐seven percent of the cohort had PSA of 10 to 20 ng/mL; 25.5% patients with PSA of 10 to 20 ng/mL and 12.4% with cT2b to T2c disease were upgraded or upstaged. In multivariable analysis, predictors of upgrading or upstaging included increasing age (P = .026), PSA (P = .001), and percent PBC (P < .001), and black race versus white (P = .035) for patients with PSA of 10 to 20 ng/mL and increasing PSA (P = .001) and percent PBC (P < .001) for patients with cT2b to T2c disease. Men with PSA of 15.0 to 20.0 ng/mL or 37.5% to 49.9% PBC with PSA of 10 to 20 ng/mL had >30% risk of upgrading or upstaging, whereas cT2b to T2c patients with <12.5% PBC or PSA <5.0 ng/mL had <10% risk. Conclusion: We found that Gleason 6 FIR patients with cT2b to T2c tumors had a low risk of harboring higher grade or stage disease and would be reasonable AS candidates, whereas patients with PSA of 10 to 20 ng/mL had a high risk and might generally be poor AS candidates.

Receipt of definitive therapy in elderly patients with unfavorable-risk prostate cancer

Conservative management of aggressive prostate cancer in the elderly without definitive therapy has been associated with a 10‐year prostate cancer‐specific mortality of approximately 50%. The authors examined the prevalence of definitive therapy in elderly patients with intermediate‐risk or high‐risk disease.

Risk of Upgrading and Upstaging Among 10 000 Patients with Gleason 3 + 4 Favorable Intermediate-risk Prostate Cancer

BACKGROUND It is unknown whether active surveillance can be safely offered to patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer. OBJECTIVE To examine the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. DESIGN, SETTING, AND PARTICIPANTS The study involved 10 089 patients in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA) <10ng/ml, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBCs) who underwent radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression was used to examine predictors of upgrading (pathologic Gleason ≥4+3 or tertiary Gleason 5 in a Gleason 7 tumor) or upstaging (pT3-4/N1). RESULTS AND LIMITATIONS Some 30.3% of Gleason 3+4 FIR patients were upgraded or upstaged. On multivariable analysis, predictors included higher PSA, percentage PBC, age, and cT2a versus cT1c (all p<0.001), but not black race (p=0.895). When stratified into ordinal variables, PSA 8.1-9.9 versus ≤4.0ng/ml (adjusted odds ratio [AOR] 1.93, 38.3% vs 24.4%), PBC 37.5-49.9% versus <12.5% (AOR 1.79, 37.8% vs 25.1%); highest age quartile (≥67 yr) versus lowest (≤55 yr; AOR 1.46, 35.7% vs 24.7%); and cT2a versus cT1c (AOR 1.33, 34.3% vs 29.8%) were associated with a higher risk of upgrading or upstaging (all p<0.001). Men with PBC <12.5% and PSA ≤4.0ng/ml had a 21.7% risk of more advanced disease. This increased to 44.3% for PBC 37.5-49.9% and PSA 8.1-9.9ng/ml. A limitation of the study is its retrospective nature. CONCLUSIONS Approximately one in three patients with Gleason 3+4 FIR harbored disease of higher grade or stage. Younger patients with low percentage PBC and PSA and cT1c disease have a lower risk and may be candidates for active surveillance. However, widely available clinical information is insufficient for predicting the risk of more advanced disease, and the development and incorporation of additional tools, including magnetic resonance imaging and genomic tests, are necessary. PATIENT SUMMARY Nearly one-third of patients with Gleason 3+4 favorable intermediate-risk prostate cancer harbor disease of higher grade or higher stage than their biopsy and clinical examination suggest. These patients would therefore be poor candidates for active surveillance.