Intensity modulated radiation therapy in prostate cancer-Better survival with higher total dose?

Abstract

Background and purpose: For patients with intermediate and high-risk prostate cancer, radiation treatment is a well-established alternative to surgery. Modern techniques, such as intensity-modulated radiation therapy and volumetric modulated arc therapy, allow for precise dose escalation to the tumor while minimizing exposure to surrounding healthy tissues. The purpose of this analysis was to assess the safety and efficacy of two different radiation treatment protocols (high dose vs low dose) in prostate cancer patients across all risk categories.

Patients and methods: Between 2015 and 2021, a total of 300 consecutive patients with localized adenocarcinoma of the prostate underwent intensity-modulated radiation therapy and volumetric modulated arc therapy at this institution. The study's endpoints were overall survival, prostate cancer specific overall survival, metastases-free survival, biochemically no evidence of disease survival rates as well as acute and long-term toxic effects. Influence of patient- and treatment-related parameters, including risk stratification (low and medium vs. high risk), radiation therapy dose levels (< 76 Gy vs. ≥ 76 Gy), radiation therapy duration (≤ 51 days vs. > 51 days), treatment with or without elective node irradiation, and the use of concurrent androgen deprivation therapy was evaluated by the log-rank-test and using multivariate Cox-analysis.

Results: Overall survival, prostate cancer specific overall survival, metastases-free survival and biochemically no evidence of disease survival rates were 88%, 96%, 94%, 92% and 56%, 76%, 90%, 75% at 5 and 10 years, respectively. Univariate analysis identified a significant impact of total dose and androgen deprivation therapy. Overall survival rates for patients with a total radiation dose ≥ 76 Gy were 92% and 59% at 5 and 10 years, respectively, in comparison with patients receiving a total dose of < 76 Gy having a 5-year overall survival of 82% and a 10-year of overall survival 52% (p=0.012). Androgen deprivation therapy had an impact on overall survival with a 5-year of 90% and a 10-year of 57% survival rates, in comparison to a group without androgen deprivation therapy that had a significantly lower 5-year overall survival of 79.8% and a 10-year overall survival of 23.8% (p=0.041). In multivariate analysis, total radiation dose remained of significant impact on overall survival (p=0.022) and risk grouping (p=0.026) on biochemically no evidence of disease survival. Regarding toxicity, Grade II and III late genitourinary toxicity was observed in 13 patients (4.3%), and late gastrointestinal toxicity of similar grade affected 12 patients (4%) in the cohort.

Conclusion: Data from this retrospective analysis underscore the highly relevant influence of total dose in contemporary radiation treatment of patients with prostate cancer.

Keywords: Androgen deprivation therapy; Dose escalation; IMRT; Pelvic radiation; Prostate cancer; Radiation therapy; Toxicities; VMAT.