A Phase I Trial of Neoadjuvant Stereotactic Body Radiotherapy (SBRT) Prior to Radical Prostatectomy (RP) in Locally Advanced Prostate Cancer

PURPOSE/OBJECTIVE(S) Many men with locally advanced prostate cancer who undergo RP develop recurrence and require additional therapy. We hypothesized that neoadjuvant SBRT followed by RP may be a convenient, safe, and effective method to provide multi-modality therapy. Herein, we report the results of our phase I trial of neoadjuvant SBRT followed by RP in locally advanced prostate cancer. MATERIALS/METHODS Men with high-risk and clinical node positive prostate cancer were enrolled between 3/2017-10/2017 on a single center phase I trial (NCT02946008). The primary endpoint was 30-day post-RP complications based on operative blood loss, length of stay, readmission, drain or catheter replacement, with a composite goal of ≤28% of patients experiencing a dose-limiting toxicity (DLT), using a continual reassessment method. Dose level 0 and 1 delivered 30 Gy and 35 Gy in 5 fractions to the prostate/seminal vesicles, respectively. All patients received 25 Gy/5 fractions to the pelvic lymph nodes. RP was performed 4-10 weeks after SBRT. No hormone therapy was used. Acute and late toxicities were evaluated by CTCAE v.4.0. Quality of life (QoL) outcomes were obtained with the Expanded Prostate Cancer Index Composite (EPIC-26). RESULTS Median follow-up was 40 months (range, 33-44). Although the study was deemed safe by the 30-day primary endpoint (25% of patients experienced a DLT), the trial was stopped early after enrollment of 16 patients (38 originally planned) due to onset of late adverse events. RP was performed at a median of 6 weeks (range, 5-10). No grade 3 toxicities occurred during or post-SBRT/pre-RP. Post-RP, grade 3+ GU and GI toxicities occurred in 75% and 25% of patients, respectively. Two patients required cystectomy and urinary diversion ≥2 years post-RP. Mean EPIC QoL scores at baseline, post-SBRT/pre-RP, 3 months, 12 months and 24 months post-RP for urinary incontinence: 90 (82-99), 91 (84-97), 14 (5-22), 25 (7-42), and 42 (17-68); sexual function: 70 (54-85), 67 (50-83), 7 (2-12), 12 (5-20), 22 (10-34). No patients reported bothersome rectal bleeding. Seven patients (43%) had a biochemical recurrence, and five patients (31%) developed distant metastases. No patients developed a local or regional recurrence. CONCLUSION Neoadjuvant SBRT to 30-35 Gy in 5 fractions followed by RP results in unacceptably high toxicity and severe QoL declines. Locoregional only treatment intensification is oncologically inadequate, as nearly half of men having recurred by 3 years post-treatment. Given the success of definitive radiotherapy plus hormone therapy in locally advanced prostate cancer, the combination of neoadjuvant SBRT and RP should not be further pursued.