3352 - Estimation of a/ß Ratio for Late Genitourinary Toxicity Following Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer
Presenter(s)
S. Takano1, N. Tomita1, T. Takaoka1, D. Okazaki1, M. Niwa1, A. Torii1, N. Kita1, M. Oguri1, M. Imai2, T. Mizuno3, K. Nomura4, S. Otsuka5, S. Ayakawa6, Y. Manabe7, A. Miyamoto8, Y. Ogawa9, A. Miyakawa10, T. Yasui11, and A. Hiwatashi1; 1Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 2Department of Radiology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan, 3Department of Radiation Oncology, Suzuka General Hospital, Suzuka, Japan, 4Department of Radiotherapy, Nagoya City West Medical Center, Nagoya, Japan, 5Department of Radiology, Okazaki City Hospital, Okazaki, Japan, 6Department of Radiation Oncology, Japan Community Health care Organization Chukyo Hospital, Nagoya, Japan, 7Department of Radiation Oncology, Nanbu Tokushukai General Hospital, Okinawa, Japan, 8Department of Radiation Oncology, Hokuto Hospital, Obihiro, Japan, 9Department of Radiation Oncology, Kasugai Municipal Hospital, Kasugai, Japan, 10Department of Radiation Oncology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan, 11Department of Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Purpose/Objective(s): In salvage radiotherapy (SRT) for biochemically recurrent prostate cancer, our previous study showed that slight hypofractionation (2.1–2.3 Gy/fraction) was associated with an increased risk of late genitourinary (GU) toxicity. We hypothesized that this may be attributed to a lower a/ß ratio for the postoperative bladder compared to the traditionally assumed a/ß values (3–5 Gy) from definitive radiotherapy. This study aimed to estimate the a/ß ratio for late GU toxicity after SRT.
Materials/Methods: We identified 153 eligible patients treated with SRT for biochemically recurrent prostate cancer after radical prostatectomy between 2008 and 2018 at 10 institutions. Eligibility required image-guided intensity-modulated radiotherapy without whole-pelvic radiotherapy. SRT was delivered to the prostate and seminal vesicle bed at a median (range) dose of 66 Gy (63.8–78.2) in 1.8–2.3 Gy fractions. Dose-volume histograms of the bladder were extracted in 1 Gy increments. Late grade =2 (=G2) GU toxicity was modeled using the Lyman-Kutcher-Burman (LKB) and relative seriality (RS) models, with both EQD2-converted (LKB-EQD2, RS-EQD2) and non-EQD2-converted versions (LKB-NoEQD2, RS-NoEQD2). Maximum likelihood estimation with 1000 bootstrap samples was used to compute the 95% confidence intervals (CIs) for model parameters. Nested models were compared using the likelihood ratio test.
Results: With a median follow-up duration of 62 months, the 5-year cumulative incidence of late =G2 GU toxicity was 16% (95% CI, 10.5–22.5%). The most common toxicities were =G2 hematuria (16 patients, 11%), =G2 incontinence (5 patients, 3%), and =G2 urinary tract obstruction (4 patients, 3%). EQD2-converted models tended to provide better fits compared to non-EQD2-converted models (P = 0.12 for LKB, P = 0.047 for RS). For late =G2 GU toxicity, EQD2-converted models yielded low a/ß estimates (<0.50 Gy): for LKB-EQD2, a/ß = 0.01 Gy (95% CI, 0.01–0.01 Gy), TD50 = 88.0 Gy (95% CI, 72.4–510 Gy), m = 0.25 (95% CI, 0.11–0.93), and n = 0.02 (95% CI, 0.01–0.11); for RS-EQD2, a/ß = 0.01 Gy (95% CI, 0.01–0.46 Gy), D50 = 78.2 Gy (95% CI, 69.5–125 Gy), ? = 2.51 (95% CI, 0.56–8.63), and s = 6.02 (95% CI, 1.59–20.5). The 95% CIs for endpoint-specific a/ß estimates were also low: =G2 incontinence (LKB-EQD2: 95% CI, 0.01–0.78 Gy, RS-EQD2: 95% CI, 0.01–0.03 Gy), =G2 urinary tract obstruction (LKB-EQD2: 95% CI, 0.01–0.75 Gy, RS-EQD2: 95% CI, 0.01–0.83 Gy), and =G2 hematuria (LKB-EQD2: 95% CI, 0.01–1000 Gy, RS-EQD2: 95% CI, 0.01–0.17 Gy).
Conclusion: This study estimated an a/ß ratio for late =G2 GU toxicity after SRT to be <0.5 Gy. These results suggest that the postoperative bladder may have high sensitivity to larger radiation doses per fraction. Given the typical a/ß ratio for prostate cancer (1.5 Gy), the therapeutic benefit of hypofractionation in the salvage setting may be more limited than expected.