Survival of men with gleason score (GS) 8–10 adenocarcinoma of the prostate treated with external beam radiation therapy

Abstract

Four risk groups have been previously defined by the RTOG that allowed prediction of disease specific survival (DSS). Based on this study, patients with GS 8–10 and clinical stages of T1-2 and T3 corresponding to RTOG risk groups 3 and 4 were estimated to have a 5 year DSS of 83% and 64% respectively. However, most of these patients were treated before 1992 using older techniques and all treated with radiation alone. These same risk groups had a 5 year DSS of 93% and 81% respectively when treated with long term hormonal therapy (HT). This retrospective single institution study was designed to determine whether we could detect a noticeable change in the expected survival rates of patients with GS 8–10 treated with modern techniques. A total of 81 patients with T1-3 GS 8–10 adenocarcinoma of the prostate were treated with external beam radiation therapy from July 1987 to December 1996 and were included in this study. Median follow up for all patients and for the 37 living patients was 58.8 months and 87.8 months respectively. A modified ASTRO definition of biochemical failure was used. The date of failure was the midpoint between the date of the last PSA prior to the first of three rising values and the date of the first rising value. For patients treated with hormone therapy, the third value must be > 1.5ng/ml. Any patient started on HT after treatment was classified as a failure. Failure distributions were compared using the log rank test. Independent predictors of outcome were identified using the likelihood ratio test (LLRT) to compare models using Cox’s proportional hazard method. Among this high grade cohort, 47% had T3 disease and 68% had either T3 disease or pretreatment PSA (pPSA) > 20ng/ml. 41% of patients were treated after 1993 and were more likely to have received a maximum dose (Dmax) > 72 Gy (56% vs. 100%, p < 0.0001), more likely to be treated with 3D conformal radiation therapy (3DCRT) (60% vs. 100%, p < 0.0001), more likely to have neoadjuvant or adjuvant HT as a component of treatment (10% vs. 52%, p < 0.0001), and less likely to have T3 and pPSA > 20 disease (31% vs. 9%, p = 0.02). Despite these differences related to treatment era, no difference was found in biochemical failure, DSS or overall survival (OS) for patients treated through 1993 vs. after 1993. The mean Dmax for all patients was 74.9 Gy ranging from 61.2–81.0 Gy. The median biochemical control rate was 35 months with 38% remaining disease free at 5 years. With multivariate analyses, having pPSA > 20 with T3 disease was the strongest predictor of biochemical failure (LRRT: p = 0.002). Although only 27% of the patients received neoadjuvant or adjuvant HT, the use of HT contributed to more favorable biochemical control (LRRT: p = 0.03). No other factors were found to be significant independent predictors for biochemical control. The 5 year OS and DSS for all patients were 69% and 87% respectively. The five year DSS estimates by T stage corresponding to RTOG risk groups 3 and 4 were 88% for T1 and T2 and 84% for T3. When pPSA, treatment era, whole pelvis vs. prostate RT alone, Dmax, age, and use of hormones were considered simultaneously, none were significant predictors of OS. These patients with GS 8–10 who were treated primarily with radiotherapy alone continue to do poorly with 2/3 of patients having biochemical failure by 5 years. However, DSS in this investigation appears to be at least comparable to that observed by the RTOG for patients in risk groups 3 and 4 despite the fact that few of our patients received long term HT. This may be due to our consistent use of higher doses. The addition of long term HT and higher doses is likely to result in further improvements in outcome