Rebecca G Levin-Epstein1, Naomi Y Jiang1, Xiaoyan Wang2, Shrinivasa K Upadhyaya3, Sean P Collins4, Simeng Suy4, Nima Aghdam4, Constantine Mantz5, Alan J Katz6, Leszek Miszczyk7, Aleksandra Napieralska7, Agnieszka Namysl-Kaletka7, Nicholas Prionas8, Hilary Bagshaw8, Mark K Buyyounouski8, Minsong Cao1, Nzhde Agazaryan1, Audrey Dang9, Ye Yuan1, Patrick A Kupelian1, Nicholas G Zaorsky10, Daniel E Spratt11, Osama Mohamad12, Felix Y Feng12, Brandon A Mahal13, Paul C Boutros14, Arun U Kishan1, Jesus Juarez1, David Shabsovich1, Tommy Jiang1, Sartajdeep Kahlon1, Ankur Patel1, Jay Patel1, Nicholas G Nickols15, Michael L Steinberg1, Donald B Fuller16, Amar U Kishan17. 1. Department of Radiation Oncology, University of California, Los Angeles, USA. 2. UCLA Division of General Internal Medicine and Health Services Research, USA. 3. Department of Biological and Agricultural Engineering, University of California, Davis, USA. 4. Department of Radiation Medicine, Georgetown University Hospital, USA. 5. 21st Century Oncology, Inc., Fort Myers, USA. 6. FROS Radiation Oncology and CyberKnife Center, Flushing, USA. 7. Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, Poland. 8. Department of Radiation Oncology, Stanford University Medical Center, USA. 9. Department of Radiation Oncology, Tulane Medical Center, New Orleans, USA. 10. Department of Radiation Oncology, Penn State Cancer Institute, Hershey, USA. 11. Department of Radiation Oncology, University of Michigan, Ann Arbor, USA. 12. Department of Radiation Oncology, University of California San Francisco, USA. 13. Department of Radiation Oncology, University of Miami, USA. 14. Department of Human Genetics, University of California, Los Angeles, USA; Department of Urology, University of California, Los Angeles, USA. 15. Department of Radiation Oncology, University of California, Los Angeles, USA; Department of Radiation Oncology, West Los Angeles Veterans Health Administration, USA. 16. Department of Radiation Oncology, Genesis Healthcare, USA. 17. Department of Radiation Oncology, University of California, Los Angeles, USA; Department of Urology, University of California, Los Angeles, USA. Electronic address: aukishan@mednet.ucla.edu.
Abstract
BACKGROUND AND PURPOSE: The optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens. MATERIALS AND METHODS: In 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS). RESULTS: Median follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p < 0.0001). The 38/4 cohort demonstrated the steepest PSA decay slope and greater odds of nPSA ≤0.2 ng/mL (both p < 0.0001 vs. all other regimens). BCR occurred in 6.25%, 6.75%, 3.95%, and 8.95% of men treated with 35/5, 36.25/5, 40/5, and 38/4, respectively (p = 0.12), with the highest BCRFS after 40/5 (vs. 35/5 hazard ratio [HR] 0.49, p = 0.026; vs. 36.25/5 HR 0.42, p = 0.0005; vs. 38/4 HR 0.55, p = 0.037) including the entirety of follow-up, but not for 5-year BCRFS (≥93% for all regimens, p ≥ 0.21). CONCLUSION: Dose-escalation was associated with greater prostate ablation and PSA decay. Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS. Biochemical control remains excellent, and prospective studies will provide clarity on the benefit of dose-escalation.
BACKGROUND AND PURPOSE: The optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens. MATERIALS AND METHODS: In 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS). RESULTS: Median follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p < 0.0001). The 38/4 cohort demonstrated the steepest PSA decay slope and greater odds of nPSA ≤0.2 ng/mL (both p < 0.0001 vs. all other regimens). BCR occurred in 6.25%, 6.75%, 3.95%, and 8.95% of men treated with 35/5, 36.25/5, 40/5, and 38/4, respectively (p = 0.12), with the highest BCRFS after 40/5 (vs. 35/5 hazard ratio [HR] 0.49, p = 0.026; vs. 36.25/5 HR 0.42, p = 0.0005; vs. 38/4 HR 0.55, p = 0.037) including the entirety of follow-up, but not for 5-year BCRFS (≥93% for all regimens, p ≥ 0.21). CONCLUSION: Dose-escalation was associated with greater prostate ablation and PSA decay. Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS. Biochemical control remains excellent, and prospective studies will provide clarity on the benefit of dose-escalation.
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