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

Abstract

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. Materials and Methods: 79 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, and 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 of 45 to 54 Gray (Gy) and the prostate was irradiated to a dose of 65 to 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 (LHRH) agonist (18 patients), or combined androgen blockade (38 patients). Prognostic factors examined included microscopic versus measurable lymph node involvement, one-sided versus two-sided disease, T-stage, pre-treatment 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. Results: Median follow-up is 6.7 years, and 20 patients (25%) have been followed for longer than 8 years. There have been 25 recurrences in the entire group including 3 local recurrences in the prostate, 7 patients with biochemical recurrences without clinical evidence of disease, 13 patients with distant metastases, and 2 patients where the location of recurrence was unknown. Patients with biochemical failure before 5 years were more likely to fail distantly: 16% versus 4% (p < 0.001). Overall actuarial survival at 5, 8, and 12 years is 86, 72, and 53%, respectively, while actuarial disease-free survival was 90, 87, and 81%. Ten patients died of intercurrent disease, and 4 of these died of a separate (non-pelvic) malignancy of non-adenocarcinomatous histology with no elevation in PSA. Of the potential prognostic variables examined, there was a trend toward increased biochemical recurrence in Gleason score ≥ 8 patients (p<0.08) and this became statistically significant when the 4 patients with known residual lymph node disease after biopsy were excluded (p<0.03). A single long-term toxic event of 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 confined metastasis to pelvic lymph nodes. All patients appear to benefit from such treatment, although there is a suggestion that patients with lower Gleason score are at decreased risk for recurrence. Combined modality therapy may also extend disease-free survival and allow patients to maintain independent function.