Prognostic Value of the Intermediate Risk Feature in Men with Favorable Intermediate Risk Prostate Cancer: Implications for Active Surveillance

Abstract

<h3>Purpose/Objective(s)</h3> Active surveillance (AS) is an appropriate treatment option for carefully selected men with favorable intermediate risk prostate cancer. Additional strategies are needed to help identify patients that are most suitable for AS. As the presence of Gleason Score (GS) 4 disease on biopsy is thought to be a stronger risk factor than a prostate-specific antigen (PSA) of 10-20, some guidelines express caution regarding the use of AS for these men. We sought to investigate whether outcomes differed for men with favorable intermediate risk prostate cancer on AS based on whether they were classified as intermediate risk due to PSA or GS. <h3>Materials/Methods</h3> We identified a cohort of patients diagnosed with localized intermediate risk prostate cancer between January 2001 and December 2015 in the United States Veterans Affairs Health System who pursued AS. AS was defined as not having received a prostatectomy, radiation, or androgen deprivation therapy in the first year from diagnosis and the receipt of at least 1 prostate biopsy after diagnosis. From this cohort, we selected patients who had a single favorable intermediate risk feature, either GS 3+3 = 6 and PSA 10-20 or a GS of 3+4 with PSA <10. Demographic data were collected including race, age, Charlson Comorbidity Index (CCI), and smoking status. Education level (% with bachelor's degree) and median income were estimated based on patient ZIP code using US census data. The primary endpoint of the study was the competing risk-adjusted cumulative incidence of receiving definitive treatment (prostatectomy or radiation). Secondary endpoints included rates of metastatic prostate cancer, prostate cancer-specific mortality (PSCM), and all-cause mortality (ACM). <h3>Results</h3> The cohort included 663 men with a median follow up of 7.5 years. A majority of patients (n=404, 60.9%) were intermediate risk due to GS only, the remainder (n=259, 30.1%) were PSA only. The GS only group was slightly younger (median age 65.1 years vs 66.3, p=0.017) but there were no other significant differences between groups in race, CCI score, smoking status, education or income. The cumulative incidence of definitive treatment at 5 years was similar in the GS only and PSA only groups (67.6% vs 63.6%, p=0.32). There were also no differences between groups in 5-year rates of metastatic disease (4.0% vs 4.4%, p=0.77), PSCM (0.5% vs 2.4%, p=0.27), or ACM (5.3% vs 5.6%, p=0.14). <h3>Conclusion</h3> Men with favorable intermediate risk prostate cancer due to GS who pursued active surveillance had similar outcomes to those who were intermediate risk due to PSA. Clinical intermediate risk features alone do not appear sufficient to risk-stratify patients for AS. Incorporation of additional data such as tumor genomic classifiers may be essential to predict outcomes after AS for intermediate risk patients.