Concurrent Radiation and Deep Hyperthermia Therapy for the Treatment of Recurrent Prostate Cancer

Abstract

Robustpreclinical and clinical data have established hyperthermia as an effective radiosensitizer which can be used in the setting of recurrent disease to enhance the therapeutic window. We present a single institution experience examining outcomes in recurrent prostate cancer (RPCA) patients treated with concurrent deep hyperthermia (DHT) and radiation (RT). We hypothesized that concurrent DHT and RT would be well tolerated and would provide durable local control without unexpected toxicity. Consecutive RPCA patients treated with concurrent DHT and pelvic RT were retrospectively analyzed. Patients received twice weekly DHT treatments in addition to daily or twice daily (BID) RT. DHT was delivered using a concentric ring radiofrequency phased array system to a target temperature of 40-43°C. Acute and late treatment associated toxicities, graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, were evaluated. Survival and control outcomes were evaluated using the Kaplan-Meier method. Eighteen patients were included for analysis. Median patient age was 69 yrs (64-82 yrs). Fifteen (83%) patients had received prior RT and 12 (67%) patients had undergone radical prostatectomy. At time of treatment, two patients had RPCA which had dedifferentiated to a small cell phenotype. Eight (44%) patients had extra-pelvic disease at time of treatment. Seventeen (94%) patients received proton RT, while 1 (6%) received photon RT. Median RT dose was 49 Gy (range 30-73.8 Gy). Five (28%) patients received BID RT. Fifteen (83%) patients also received sequential or concurrent systemic therapy including androgen deprivation therapy or chemotherapy. A total of 142 DHT treatments were administered (median of 7.5 treatments). Fourteen (78%) patients completed ≥ 75% of planned DHT treatments. Reasons for inability to complete treatment included discomfort and abnormal vital signs during DHT. Only one patient reported Grade 2 pain and pruritus attributed to concurrent RT and DHT. One acute Grade 3 RT toxicity (diarrhea) was reported. No late Grade 3+ toxicities occurred. Of ten patients (56%) treated with curative intent, 8 (44%) had no reported failures at 2-year follow up while two had distant failure and biochemical failure respectively. Three (17%) patients were treated with palliative intent for disease related pain; two reported partial relief and one reported complete pain relief. With a median follow-up of 27 months (1-46 months), 2-year failure free survival was 41.4% (95% CI: 27.8-55%), local control was 76.5% (95% CI 66.2-86.8%) and overall survival was 70.9% (95% CI 58.4-83.3%). Our results suggest that concurrent RT and DHT is well tolerated and allows for safe escalation of local therapy for RPCA, providing patients with durable local control and palliation with an acceptable toxicity profile. Prospective validation is warranted.