PSOR5 Presentation Time: 11:50 AM: Interstitial Hyperthermia and High Dose-Rate Brachytherapy Combined with Short-Term Androgen Deprivation Therapy and External-Beam Radiation in High- and Very High-Risk Prostate Cancer

Abstract

<h3>Purpose</h3> Multimodality treatment of high- and very-high risk prostate cancer has evolved tremendously in recent years to incorporate long-term androgen deprivation therapy (ADT), external-beam radiation therapy (EBRT), and brachytherapy, resulting in improved biochemical progression-free survival (bPFS). However, outcomes remain imperfect, and many patients are unwilling or unable to tolerate long-term ADT use. Existing studies show that hyperthermia is a potent and well-tolerated radiosensitizer. We report the outcomes of patients treated with short-term ADT, EBRT, and high dose-rate (HDR) brachytherapy combined with interstitial hyperthermia. <h3>Materials and Methods</h3> In a single-institution, retrospective study, we reviewed all patients with high- or very high-risk prostate adenocarcinoma who began definitive treatment between December 2016 and March 2020 with up to six months of ADT, whole-pelvis EBRT, and a combination of HDR brachytherapy boost and interstitial hyperthermia. Our primary endpoint was bPFS based on the Phoenix definition (PSA nadir +2 ng/mL) calculated from time of ADT initiation. We also report data on type of failure, survival, and toxicity. <h3>Results</h3> 56 patients were reviewed, including 21 with high-risk and 35 with very high-risk prostate adenocarcinoma. Median age was 72 years (range 52-82 years). Median duration of ADT use was 4 months (range 0-6 months). All patients received whole-pelvis EBRT of 45Gy/25fx. 55 patients (98%) received a 5.4Gy/3fx EBRT boost to the prostate and seminal vesicles. All patients received two Iridium-192 HDR implants to further boost the prostate and seminal vesicles, with each implant separated by at least one week (median 2 weeks, range 1-6 weeks) and consisting of two fractions of 5.5Gy separated by five to seven hours, for a total of 22Gy/4fx. All patients received at least one interstitial hyperthermia treatment of at least 45 minutes in between fractions of the same implant. 50 patients (89%) received both planned hyperthermia treatments of at least 60 minutes each at a goal temperature of 42-43 degrees Celsius. Median duration of follow-up was 28 months for all patients, with 34 months for high-risk and 28 months for very-high risk disease. The estimated two/three-year bPFS-rates were 100%/100% for high-risk and 92.0%/87.7% for very high-risk disease. Figure 1 represents the Kaplan-Meier curve for bPFS. Of the three very high-risk patients who failed biochemically, one failed regionally at 25 months, and two failed distantly at 15 and 23 months. There were no local failures. Two patients with very-high risk disease have died, both of unrelated lung disease at nine and 13 months. Four patients stopped their hyperthermia treatment early due to intolerance, with one developing an acute perineal burn that fully healed three months later. There were otherwise no grade 3 or higher acute toxicities. Four patients (7%) developed late grade 3 toxicities, all genitourinary-related. <h3>Conclusions</h3> Multimodality treatment of prostate cancer with short-term ADT, EBRT, HDR brachytherapy, and interstitial hyperthermia is safe and well-tolerated. For patients with high-risk disease, it provides excellent biochemical control while sparing long-term use of ADT. Patients with very high-risk disease may benefit from long-term use of ADT and/or other forms of systemic therapy. Longer follow-up and prospective trials are needed to validate our findings.