3286 - High Risk Prostate Cancer Treated with Radiation Therapy: Favorable Outcomes in Men with PSA>20 as the Sole High Risk Factor

A. Shimomura¹, A. A. Solanki², and S. Liauw³; ¹University of Chicago Medical Center, Chicago, IL, ²Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, ³Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL

Purpose/Objective(s): Within the traditional 3-tier NCCN low, intermediate, or high risk categorization for prostate cancer, it is recognized that heterogeneity can exist within each stratum. We explored clinical factors associated with disease outcome for men with high-risk prostate cancer treated with primary radiation therapy (RT). Materials/

Methods: Of 742 men with prostate cancer treated with primary RT with curative intent between 2005-2021, 282 had NCCN high-risk disease and comprised the study group. The median age was 68, and 66% of the cohort was black. Median PSA was 19 (IQR 9-38), 56% had T2b disease or greater, and Gleason score was 6/7/8/9/10 in 4%/26%/35%/32%/2%, respectively. The median RT dose was 78 Gy; 18 (6%) had brachytherapy boost. Androgen deprivation therapy (ADT) was given in 94% for a median 28 mo. Potential prognostic variables were tested on univariate and multivariable (MVA) analysis for freedom from biochemical failure (FFBF), distant metastasis (FFDM), and cause specific survival (CSS). The number of “high risk factors” including PSA>20, cT3a+ stage, and Gleason 8+ were assessed, as well as “very high risk disease” including cT3b stage, multiple high risk factors, and primary Gleason pattern 5 disease. Median follow-up was 53 mo.
Results: In men with low, favorable intermediate, unfavorable intermediate, high, and very high risk disease, the 5-y FFBF was 91/94/90/83/72, 5-y FFDM was 100/98/98/89/80, and 10-y CSS was 100/100/96/98/89 (all p<0.01). The 136 men with “very high risk” disease had inferior FFBF and FFDM compared to the other 146 men with "standard" high-risk disease (p<0.01). The number of NCCN high risk factors was 1, 2, or 3 in 157 (56%), 84 (30%), and 41 (15%) men, and was associated with 5-y FFBF (83%, 80%, 45%) and 5-y FFDM (89%, 84%, 69%, respectively, all p<0.01). 49 men had PSA>20 as the only high risk factor; this cohort had a median age 67, 88% black, 86% Gleason 7, and received a median dose of 78 Gy with ADT in 86% for a median 12 mo. Compared to others with high risk disease, men with PSA>20 as the sole risk factor had improved 5-y FFBF (94% vs 74%, p=0.05) and FFDM (97% vs 82%, p=0.02), similar to outcomes for intermediate risk disease. Meanwhile, men with Gleason 9-10 disease had inferior 5-y FFBF (68% vs 82%, p=0.01) and FFDM (78% vs 89%, p<0.01). MVA models in high-risk men revealed that Gleason score and T2b stage were associated with FFBF and FFDM (both p<0.05 in separate models), while PSA was not (p>0.6).
Conclusion: In men treated with primary RT, men with “very high risk” disease including multiple high risk factors had a poorer disease outcome. Using number of risk factors appears appropriate to stratify risk for clinical decisions, but PSA may offer the weakest prognostic value of any high risk factor. Select men with PSA>20 and cT1-2, Gleason 6-7 disease may warrant consideration of less aggressive therapy than RT with long-term ADT.