The use of stereotactic body radiation therapy (SBRT) for the definitive treatment of prostate cancer is increasing rapidly, yet the optimal dose(s) are still uncertain.13 Dose-escalation has been associated with improved biochemical and progression-free survival in conventionally fractionated external beam radiation therapy,4 but this has been minimally explored in SBRT.

The differential effect of SBRT dose on post-treatment prostate-specific antigen (PSA) kinetics has also not been directly evaluated. Various PSA nadir thresholds have been identified that may act as surrogates for early prediction of late outcomes with extended follow-up.5,6 These thresholds serve as critical tools in the interpretation and management of post-treatment PSA increases or fluctuations, as well as in the prognostication for when durable biochemical control appears likely. However, prior studies have also demonstrated that different radiation therapy modalities have differential degrees of prostate ablation and corresponding PSA decay kinetics, possibly related to the degree of dose deposition to the prostate gland.7,8 As more and more men are selecting SBRT for their care, understanding the SBRT dose-response for both PSA kinetics and biochemical control has become increasingly important.

In our study, we compared PSA kinetics and biochemical control among four commonly used prostate SBRT dose-fractionation regimens in a pooled multi-institutional analysis of 1,908 men with low-risk, intermediate-risk, and unfavorable intermediate-risk prostate cancer treated across eight institutions from 2003-2018. In order of increasing biologically equivalent dose, the regimens were: 35 Gy in 5 fractions (35/5), 36.25 Gy in 5 fractions (36.25/5), 40 Gy in 5 fractions (40/5), and 38 Gy in 4 fractions (38/4).

We observed that PSA decay kinetics followed a pattern consistent with dose-escalation, such that increasing biologically effective dose was significantly associated with a steeper slope of PSA decay, a lower PSA nadir (for 38/4 only), and a greater odds of achieving PSA threshold values of PSA 0.2 and 0.5 ng/mL. However, with respect to biochemical recurrence-free survival, 40/5 emerged as the winner compared to all other dose groups. Importantly, this finding emerged late, with no significant difference among the groups in the first five years, with 5-year biochemical recurrence-free survival rates ranging from 93-96.5%.

The finding that dose-escalation beyond the 40/5 dose level was not associated with gains in biochemical control presents the question of why 38/4, with higher biologically equivalent dose, would not provide at least comparable biochemical control. We posit that this may be due to slight imbalances in unfavorable risk patients, which though not statistically significant between groups may impact results beyond their actual clinical significance given that biochemical failures are relatively rare in the low- and intermediate-risk prostate cancer population.

Important questions that were not evaluated in our study still remain, including whether there are differences in acute or late toxicity between these regimens, and whether there are differences in patterns of disease recurrence particularly intra-prostatic versus extra-prostatic failures.

Our study is an important step in the process of solidifying the optimal prostate SBRT dose and the role of dose-escalation for localized, low- and intermediate-risk prostate cancer. However, the gold standard for evaluating this question will be a prospective trial, which we hope can be implemented in the future.

Written by: Rebecca G Levin-Epstein, Naomi Y Jiang, Xiaoyan Wang, Shrinivasa K Upadhyaya, Sean P Collins, Simeng Suy, Nima Aghdam, Constantine Mantz, Alan J Katz, Leszek Miszczyk, Aleksandra Napieralska, Agnieszka Namysl-Kaletka, Nicholas Prionas, Hilary Bagshaw, Mark K Buyyounouski, Minsong Cao, Nzhde Agazaryan, Audrey Dang, Ye Yuan, Patrick A Kupelian, Nicholas G Zaorsky, Daniel E Spratt, Osama Mohamad, Felix Y Feng, Brandon A Mahal, Paul C Boutros, Arun U Kishan, Jesus Juarez, David Shabsovich, Tommy Jiang, Sartajdeep Kahlon, Ankur Patel, Jay Patel, Nicholas G Nickols, Michael L Steinberg, Donald B Fuller, Amar U Kishan

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA., UCLA Division of General Internal Medicine and Health Services Research., Department of Biological and Agricultural Engineering, University of California, Davis, Davis, California., Department of Radiation Medicine, Georgetown University Hospital., 21(st) Century Oncology, Inc., Fort Myers, FL., FROS Radiation Oncology and CyberKnife Center, Flushing, NY., Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, Gliwice, Poland., Department of Radiation Oncology, Stanford University Medical Center., Department of Radiation Oncology, Tulane Medical Center, New Orleans, LA., Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI., Department of Radiation Oncology, University of California San Francisco, San Francisco, CA., Department of Radiation Oncology, University of Miami., Department of Human Genetics, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA., Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA; Department of Radiation Oncology, West Los Angeles Veterans Health Administration., Department of Radiation Oncology, Genesis Healthcare., Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA; Department of Urology, University of California, Los Angeles, CA, USA. Electronic address: .

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Dose-Response with Stereotactic Body Radiotherapy for Prostate Cancer: A Multi-Institutional Analysis of Pr... - UroToday