Long-term use of combined radiation therapy and hormonal therapy in the management of stage D1 prostate cancer

PURPOSE: To determine tumor response, patterns of relapse, and prognostic indicators in patients followed long-term after combined hormonal radiation therapy of adenocarcinoma of the prostate in men with tumor metastatic to pelvic lymph nodes. METHODS AND MATERIALS: Seventy-nine patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node metastases were treated with combined radiation therapy and hormonal therapy. Of these, 55 patients (70%) had T3 disease, with the remainder having earlier-stage disease; 45 (57%) patients had N2 disease (Whitmore-Jewett staging). No distant metastases were detected at initial staging, and no patient had radiographic or pathologic involvement of the para-aortic nodes. Pelvic lymph nodes were irradiated to a dose 45-54 Gy, and the prostate was irradiated to a dose 65-71.8 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose diethylstilbestrol (DES) (2 patients), orchiectomy (21 patients), luteinizing hormone-releasing hormone agonist (12 patients), or combined androgen blockade (44 patients). Prognostic factors examined included microscopic vs. measurable lymph node involvement, one-sided vs. two-sided disease, T stage, pretreatment PSA, method of androgen blockade, and Gleason score. Log-rank analysis was used to determine statistical significance with respect to overall survival, disease-free survival, clinical freedom from progression, and biochemical freedom from progression; Cox multivariate analysis was employed to determine potential confounders. RESULTS: Median follow-up was 6.7 years. There were 25 recurrences among the 79 patients, including 7 biochemical recurrences without clinical evidence of disease, three local recurrences in the prostate, and distant metastases in 14 patients; 2 patients were deceased, with cause of death listed as prostate cancer, though the location of recurrence was unknown. Patients with biochemical failure before 5 years were more likely to fail distantly, 16% vs. 4% (p < 0.001). Overall actuarial survival at 5, 8, and 12 years was 86%, 72%, and 53%, respectively, whereas actuarial disease-free survival was 90%, 87%, and 81%. Ten patients died of intercurrent disease; these included 4 patients who died of a separate (nonpelvic) malignancy of nonadenocarcinomatous histology with no elevation in PSA. When the potential prognostic variables were examined, a trend toward increased biochemical recurrence in patients with Gleason score >or=8 was observed; this became statistically significant when the 4 patients with known residual lymph node disease after biopsy were excluded (p < 0.03). Gleason score remained the only significant indicator on multivariate analysis. A single long-term toxic event, recto-ureteral fistula, was observed. CONCLUSION: Combined hormonal and radiation therapy continues to represent an effective treatment option for patients with adenocarcinoma of the prostate with metastasis confined to pelvic lymph nodes. All patient groups seem to have a better disease-free survival than that reported previously in single-modality hormone or radiation treatment series. There is a suggestion that patients with lower Gleason score have a lower risk for recurrence. Combined modality therapy may also extend disease-free survival and allow patients to maintain independent function.