A phase I pilot study of pre-operative radiotherapy for prostate cancer: Long-term toxicity and oncologic outcomes.

BACKGROUND: Neoadjuvant radiotherapy (RT) improves disease control in various cancers, and has become an established oncologic treatment strategy. During 2001-2004, we conducted a phase I pilot study assessing the role of short-course pre-operative RT (PreORT) for men with unfavourable intermediate- and high-risk localized prostate cancer. Herein, we present long-term follow-up toxicity and oncologic outcomes.

MATERIALS AND METHODS: Eligible patients had histologically proven prostate cancer, cT1-T2N0M0 disease, PSA >15-35 ng/ml regardless of Gleason score, or PSA 10-15 ng/ml with Gleason score ≥7. Patients received 25 Gy in five consecutive daily fractions (5 Gy per fraction) to the prostate-only, followed by radical prostatectomy within 14 days after RT completion. Primary outcomes were intra-operative morbidity, and late genitourinary (GU) and gastrointestinal (GI) toxicities.

RESULTS: In total, 15 patients were enrolled; 14 patients completed PreORT followed by radical prostatectomy, which also included bilateral lymph node dissections in 13 cases. Median follow-up was 12.2 years (range 6.7-16.3 years). Late GU toxicity was common, with 2 patients (13.3%) experiencing G2 toxicity, and 6 patients (40%) G3 toxicity. There were no patients with G4-5 late GU toxicity. Late GI toxicity was infrequent, with only 1 patient (6.7%) experiencing transient G2 proctitis. At last follow-up, 8 (53.3%) and 6 (40%) patients experienced biochemical and metastatic disease recurrence, respectively.

CONCLUSION: The use of PreORT in men with high-risk prostate cancer is associated with unexpected high-rates of late GU toxicity. Future studies examining the role of RT pre-radical prostatectomy must cautiously select RT technique and dose schedule. Importantly, long-term follow-up data is essential to fully determine the therapeutic index of PreORT in the management of localized disease.