West Virginia University School of Medicine Morgantown, WV, United States
P. M. Shaikh Jr1, J. A. A. Vargo IV2, M. M. Fareed1, M. T. Khasawneh3, D. A. Clump II4, F. Alite Jr5, M. J. Wu6, T. Altoos7, N. Markovic8, M. M. Harkenrider9, and G. M. Jacobson10; 1Department of Radiation Oncology, West Virginia University, Morgantown, WV, 2UPMC Cancer Center, Pittsburgh, PA, 3Department of Systems Science and Industrial Engineering at Binghamton University, Binghamton, NY, 4West Virginia University Department of Radiation Oncology, Morgantown, WV, 5Geisinger Cancer Institute, Danville, PA, 6Loyola University Chicago, Chicago, IL, 7Pinellas Radiation Oncology Associates, Clearwater, FL, 8Ludwigs-Maximilians-Universität, München, Germany, 9Loyola University Medical Center, Maywood, IL, 10H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Purpose/Objective(s): We aimed to conduct the most extensive and detailed meta-analysis to date, synthesizing data from existing randomized clinical trials (RCTs) to evaluate the effectiveness and safety of hypofractionated radiotherapy (HFRT) versus conventionally fractionated, dose-escalated radiotherapy (CFRT) in the treatment of localized prostate cancer. Materials/
Methods: We searched Medline and relevant conference proceedings for RCTs comparing the outcomes of HFRT (dose per fraction between 2.4 to 4.5 Gy) and CFRT (dose per fraction between 1.8 to 2.0 Gy) in patients with localized prostate cancer. RCTs were excluded if the CFRT dose was below 74 Gy or the HFRT dose had an equivalent dose in 2 Gy fractions (EQD2) of less than 74 Gy, rounded. The primary outcome was biochemical and/or clinical progression-free survival (BCPFS), with secondary outcomes including prostate-cancer-specific survival (PCSS), overall survival (OS), as well as acute and late genitourinary (GU) and gastrointestinal (GI) toxicities. Survival outcomes were analyzed using hazard ratios (HR), while odds ratios (OR) were employed for toxicity data. Depending on heterogeneity, analyses were conducted using either a random-effects (RE) or a fixed-effect model (FE). Results: Ten RCTs comprising a total of 6,267 patients were analyzed. One three-arm trial had an arm with a lower dose HFRT (57 Gy in 19 fractions) and this arm was excluded due to its EQD2 being less than 74 Gy. Pooled analysis showed a statistically significant improvement in BCPFS for HFRT over CFRT (HR = 0.87; 95% CI: 0.77, 0.98, p=0.02, FE). Available subgroup data was pooled and showed significant benefit in Gleason <6 (p=0.03, FE), PSA between 10-20 (p=0.03, FE) and age > 70 (p=0.01, FE). There was a trend towards significance in intermediate risk ((p=0.06, FE) and cT1-2 (p=0.08, FE) disease. No significant differences were observed in PCSS (HR = 0.83; 95% CI: 0.52, 1.32, p=0.43, FE) or OS (HR = 0.90; 95% CI: 0.77, 1.04, p=0.15, FE). HFRT was associated with a significant increase in acute grade 2+ GI toxicity (25.7% vs. 18.2%, OR=1.61, 95% CI: 1.40, 1.85, p<0.00001, FE) and a modest but statistically significant increase in grade 2+ late GU toxicity (21.4% vs. 19.5%, OR=1.14, 95% CI: 0.997, 1.296, p=0.0499, FE). There was no significant difference in acute grade 2+ GU toxicity (41.2% vs. 41.8%, p=0.83, FE) or late grade 2+ GI toxicity (14.2% vs. 13.4%, p=0.65, RE). Conclusion: HFRT demonstrates a statistically significant improvement in BCPFS for patients with localized prostate cancer when compared to CFRT. No PCSS or OS differences were observed. The benefit in BCPFS is achieved at the cost of a slight increase in both acute GI and late GU toxicities. The findings support the consideration of HFRT as the preferred option for the treatment of localized prostate cancer, balancing improved biochemical control against a modest increase in toxicities.
