High efficacy of hypofractionated proton therapy with 4 fractions of 5 Gy as a boost to 50 Gy photon therapy for localized prostate cancer

Purpose: We report the outcome of hypofractionated proton boost as an alternative to high dose-rate brachytherapy boost, aimed at an equivalent dose exceeding 86 Gy in 2 Gy fractions, for patients with localized prostate cancer and all risk groups.

Methods: Proton boost of 20 Gy given in 4 daily fractions to the prostate was followed after a one-week rest by photon therapy to 50 Gy in 2 Gy fractions. Outcomes are presented per risk group according to both NCCN and ISUP classifications. Advanced imaging was performed for adequate staging, and at an early stage of rising PSA, to identify the relapse site. Endpoints were PSA relapse-free-, locoregional relapse-free-, and distant metastasis-free- survival. Prostate cancer-specific-, metastasis-free-, and overall survival were also estimated. Genitourinary (GU) and gastrointestinal (GI) toxicity were based on patients' questionnaires and physicians' records.

Results: We treated 531 patients between 2002 and 2015; 504 had localized disease. The cohort included 180 patients with T3/T4 disease (36%). The majority of the 50% with high-/very high-risk disease received ADT, 9-24 months; 92 had adjuvant pelvic node treatment. Median follow-up was 113 months (43-193). For low-, intermediate-, high-, and very high-risk patients, the 5-year PSA relapse-free survival was 100%, 94%, 82%, and 72%, respectively. Prolonged ADT improved biochemical control and nodal treatment regional control. The NCCN classification had higher predictive discrimination than the ISUP classification. The 5-year prevalence grade 3+ was 2% for GU and 0% for GI toxicity in pre-treatment symptom-free patients, and not worsened by nodal treatment.

Conclusion: Dose escalation with hypofractionated proton boost was as effective as reported with high dose-rate brachytherapy boost, and the GU and GI toxicity profile was very similar. The proton boost was also appropriate for patients with larger prostate volume, higher T-stage, and high-risk disease encompassing elective regional node photon therapy.