Is There A Role For Local Therapy Alone In Treatment Of High Grade Prostate Cancer?: Assessment Of Outcome With Radical Prostatectomy

Patients with high-grade clinically localized disease often have disease beyond the prostate and if so are likely to fail treatment with radical prostatectomy or radiation alone. Results of RTOG 92–02 indicate the subgroup of clinical T2c-T4 patients with Gleason 8–10 who received long-term androgen suppression therapy (AST) had improved survival and likewise survival benefit was demonstrated with long-term AST in a phase III EORTC study that included a minority of patients eligible based on high grade Gleason Score alone. These finding suggest that AST may be needed to address micrometastatic disease in patients with aggressive prostate cancer. However, most patients on phase III studies to date demonstrating advantage to long-term AST have had other adverse risk factors in addition to high-grade disease. The objective of this study was to assess whether use of other known prognostic factors could be helpful in determining which men with Gleason 8–10 prostate cancer might be successfully managed with local therapy alone. A retrospective analysis was performed on men with biopsy Gleason 8–10 prostate cancer who underwent radical prostatectomy at two major university centers. No patients received AST as part of initial treatment or adjuvant radiation therapy. Surgery was performed using a retropubic approach and lymph node dissection was performed in all patients. Risk groups were defined based on PSA and percent positive biopsy cores (%PBC). A cox proportional hazards analysis was performed to assess for differences in pre-treatment prognostic factors. Kaplan-Meier curves were generated for each group and then comparisons between groups was performed using Log-rank analysis to assess for differences in 5-year actuarial freedom from biochemical failure. 194 patients with Gleason 8–10 underwent radical prostatectomy between 1987 and 2002. 168 had sufficient data for analysis. Median follow-up was 18 months (range 1–130 months) with 31 patients at risk for over 5-years. Patients with PSA <10ng/ml and %PBC <50% had a 5 year actuarial biochemical control rate of 67% Vs. 23% percent for all other patients. (p < 0.001). PSA and %PBC are useful in selecting a sub-group of patients with high-grade prostate cancer most likely to benefit by radical prostatectomy. These findings suggest that long-term androgen suppression is probably not needed for all patients with high-grade prostate cancer due to lack of micrometastatic disease in many men with otherwise favorable prognositic factors. Therefore, strategies including radiation, inclusive of wider treatment fields than possible with prostatectomy and use of dose escalation warrant further investigation in this high-risk patient population.