1084 - Prospective Phase II Trial of Short Course Androgen Deprivation, Pelvic SBRT, and Brachytherapy Boost for NCCN High-Risk Prostate Cancer with Low-Intermediate Risk Decipher Genomic Score
Presenter(s)
A. G. Goglia1, M. A. Kollmeier1, S. M. McBride1, B. R. Mychalczak1, R. M. Gewanter1, D. Guttman1, D. Shasha1, B. A. Mueller1, M. B. Bernstein2, D. R. Parikh1, M. J. Zelefsky3, H. Nagar2, and D. J. Gorovets1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Memorial Sloan Kettering Cancer Center, New York, NY, 3NYU Langone Health, New York, NY
Purpose/Objective(s): The NCCN high risk category accounts for roughly 30% of all newly diagnosed cases of localized prostate cancer. While these patients are at higher risk of recurrence, distant metastasis, and death, more than 70% of high risk patients treated with definitive radiotherapy and androgen deprivation therapy (ADT) never develop metastatic disease. These findings suggest that there is a group of high risk patients whose disease biology does not match their NCCN risk category and are thus being over-treated. The Decipher genomic classifier is a gene expression-based assay commonly used as an additional risk stratification tool; its prognostic value has been retrospectively validated but has not yet been studied prospectively. We hypothesized that favorable genomic classifier scores could identify patients with NCCN high-risk prostate cancer that are suitable for de-intensification of ADT and a compressed course of radiation therapy.
Materials/Methods: This single arm, phase II prospective study enrolled 50 patients with a Decipher genomic classifier (GC) score =0.6 and localized, high-risk prostate cancer defined as Gleason grade group 4 or 5, PSA > 20 ng/mL, or cT3-4N0M0. Patients were treated with 6 months of neoadjuvant/concurrent/adjuvant ADT (leuprolide + bicalutamide) combined with a single 15 Gy Ir-192 HDR brachytherapy implant followed by 25 Gy in 5 daily fractions whole pelvis SBRT. The primary endpoint was 3-year metastasis rate. Only early toxicity (CTCAE v5.0), International Prostate Symptom Score (IPSS), and biochemical recurrence rate (defined as PSA nadir + 2 ng/mL) are reported.
Results: The median age of enrolled patients was 68.5 years old, with a median Decipher GC score of 0.405 [95%CI 0.361 – 0.433], and median baseline PSA of 6.83 [95%CI 5.98 - 8.77]. Pre-treatment MR imaging showed PIRADS 4 or 5 lesions in 84% of enrolled patients (42/50) and pre-treatment biopsies showed Gleason grade group 4 or 5 disease in 64% of patients (32/50). The median follow-up across all enrolled patients was 22 months [95%CI 19.69 – 23.55], and thus only early secondary endpoint outcomes are reported. Median baseline IPSS was 4 [95%CI 3.93 - 6.15], while median IPSS at first follow up was 9.54 [95%CI 7.73 - 11.35] and at most recent follow up was 6.62 [95%CI 5.09 - 8.14]. Grade 2 GU toxicity was seen in 32% of patients (16/50), while grade 2 GI toxicity was seen in 14% of patients (7/50). No grade 3 or higher toxicities were seen. Median time to testosterone recovery was 10 months [95%CI 9.34 - 11.03]. The rate of biochemical recurrence was 2% (1/50).
Conclusion: Thus far, we have thus far observed low GU/GI toxicity, preserved GU quality of life, and encouraging early oncological outcomes with a shorter course of ADT and RT for genomically lower risk, NCCN high-risk prostate cancer patients. Longer follow-up is needed to report the primary endpoint of 3-year metastasis-free survival.