Dose–response with stereotactic body radiotherapy for prostate cancer: A multi-institutional analysis of prostate-specific antigen kinetics and biochemical control

• Published in: Radiotherapy and oncology Vol. 154; pp. 207 - 213
• Main Authors: Levin-Epstein, Rebecca G., Jiang, Naomi Y., Wang, Xiaoyan, Upadhyaya, Shrinivasa K., Collins, Sean P., Suy, Simeng, Aghdam, Nima, Mantz, Constantine, Katz, Alan J., Miszczyk, Leszek, Napieralska, Aleksandra, Namysl-Kaletka, Agnieszka, Prionas, Nicholas, Bagshaw, Hilary, Buyyounouski, Mark K., Cao, Minsong, Agazaryan, Nzhde, Dang, Audrey, Yuan, Ye, Kupelian, Patrick A., Zaorsky, Nicholas G., Spratt, Daniel E., Mohamad, Osama, Feng, Felix Y., Mahal, Brandon A., Boutros, Paul C., Kishan, Arun U., Juarez, Jesus, Shabsovich, David, Jiang, Tommy, Kahlon, Sartajdeep, Patel, Ankur, Patel, Jay, Nickols, Nicholas G., Steinberg, Michael L., Fuller, Donald B., Kishan, Amar U.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-01-2021
• Subjects: Biochemical control; Dose-escalation; Dose–response; Humans; Kinetics; Male; Prospective Studies; Prostate cancer; Prostate-Specific Antigen - metabolism; Prostatic Neoplasms - radiotherapy; Prostatic Neoplasms - surgery; Radiosurgery; SBRT; Stereotactic body radiation therapy; Biochemical control; Dose–response; Stereotactic body radiation therapy; Dose-escalation; Prostate cancer; SBRT
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2020.09.053

•Dose-escalation was associated with greater prostate ablation and PSA decay.•All dose groups in our study achieved median nPSAs of ≤0.2 ng/mL.•Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS.•Rates of BCR were low across all dose groups, with 5-year BCRFS estimates of at least 93%.
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.
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).
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).
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.