Metformin Active Surveillance Trial in Low-Risk Prostate Cancer
Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.
Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial
Author(s): Jeff M. Michalski, MD, MBA1; Kathryn A. Winter, MS2; Bradley R. Prestidge, MD3; Martin G. Sanda, MD4; Mahul Amin, MD5; William S. Bice, PhD6; Hiram A. Gay, MD1; Geoffrey S. Ibbott, PhD7; Juanita M. Crook, MD8; Charles N. Catton, MD9; Adam Raben, MD10; Walter Bosch, DSc1; David C. Beyer, MD11; Steven J. Frank, MD7; Michael A. Papagikos, MD12; Seth A. Rosenthal, MD13; H. Joseph Barthold, MD14; Mack Roach, III, MD15; Jennifer Moughan, MS2; and Howard M. Sandler, MD16
Source: DOI: 10.1200/JCO.22.01856 Journal of Clinical Oncology 41, no. 24 (August 20, 2023) 4035-4044.
Dr. Maen Hussein's Thoughts
Our radiation oncologists will find this article particularly interesting – more radiation is NOT better.
PURPOSE
To determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer.METHODS
Men with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd). BT arm was delivered to prostate only (145 Gy if 125-Iodine, 125 Gy if 103-Pd). The primary end point was FFP: PSA failure (American Society for Therapeutic Radiology and Oncology [ASTRO] or Phoenix definitions), local failure, distant failure, or death.RESULTS
Five hundred eighty-eight men were randomly assigned; 579 were eligible: 287 and 292 in COMBO and BT arms, respectively. The median age was 67 years; 89.1% had PSA < 10 ng/mL, 89.1% had GS 7, and 66.7% had T1 disease. There were no differences in FFP. The 5-year FFP-ASTRO was 85.6% (95% CI, 81.4 to 89.7) with COMBO compared with 82.7% (95% CI, 78.3 to 87.1) with BT (odds ratio [OR], 0.80; 95% CI, 0.51 to 1.26; Greenwood T P = .18). The 5-year FFP-Phoenix was 88.0% (95% CI, 84.2 to 91.9) with COMBO compared with 85.5% (95% CI, 81.3 to 89.6) with BT (OR, 0.80; 95% CI, 0.49 to 1.30; Greenwood T P = .19). There were no differences in the rates of genitourinary (GU) or GI acute toxicities. The 5-year cumulative incidence for late GU/GI grade 2+ toxicity is 42.8% (95% CI, 37.0 to 48.6) for COMBO compared with 25.8% (95% CI, 20.9 to 31.0) for BT (P < .0001). The 5-year cumulative incidence for late GU/GI grade 3+ toxicity is 8.2% (95% CI, 5.4 to 11.8) compared with 3.8% (95% CI, 2.0 to 6.5; P = .006).CONCLUSION
Compared with BT, COMBO did not improve FFP for prostate cancer but caused greater toxicity. BT alone can be considered as a standard treatment for men with intermediate-risk prostate cancer.Author Affiliations
1Washington University—Siteman Cancer Center, St. Louis, MO;2NRG Oncology Statistics and Data Management Center/ACR, Philadelphia, PA;3Bon Secours DePaul Medical Center, Norfolk, VA;4Emory University Hospital/Winship Cancer Institute, Atlanta, GA;5University of Tennessee Health Science Center, Memphis, TN;6John Muir Medical Center, Walnut Creek, CA;7University of Texas MD Anderson Cancer Center, Houston, TX;8BCCA-Cancer Centre for the Southern Interior, Kelowna, British Columbia, Canada;9University Health Network-Princess Margaret Hospital, Toronto, Ontario, Canada;10Delaware/Christiana Care NCI Community Oncology Research Program, Newark, DE;11Arizona Oncology Services Foundation, Tucson, AZ;12Novant Health New Hanover Regional Medical Center—Zimmer Cancer Institute, Wilmington, NC;13Sutter Cancer Research Consortium, Roseville, CA;14Beth Israel Deaconess Hospital-Plymouth, Plymouth, MA;15UCSF Medical Center-Mount Zion, San Francisco, CA;16Cedars-Sinai Medical Center, Los Angeles, CARelated Articles
177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study
For our radiation oncology colleagues, the addition of PSMA-directed therapy prior to stereotactic body radiation therapy (SBRT) improved progression-free survival (PFS) in patients with oligometastatic prostate cancer. Two cycles of PSMA-directed therapy were administered before SBRT.
Development and Validation of an Artificial Intelligence Digital Pathology Biomarker to Predict Benefit of Long-Term Hormonal Therapy and Radiotherapy in Men With High-Risk Prostate Cancer Across Multiple Phase III Trials
A new MMAI-derived digital pathology biomarker was trained and prospectively validated across multiple NRG/RTOG phase III trials, including RTOG 9202 (N=1,192), to predict which high-risk/locally advanced PCa patients benefit from LT-ADT vs ST-ADT with RT. In the overall cohort, LT-ADT reduced DM (17% vs 26% at 15 years) and DDM (15% vs 23% at 15 years), but this benefit was limited to biomarker-positive patients (DM: 19% vs 33%; DDM: 19% vs 30%), with no advantage seen in biomarker-negative patients (DM: 11% vs 11%; DDM: 9% vs 10%). This tool could allow about a third of our "high-risk" patients to avoid two extra years of ADT without compromising metastasis outcomes, while ensuring we intensify for those most likely to benefit. In short, this is a practical step toward personalizing ADT duration and sparing toxicity for a significant subset of our patients.
European Study of Prostate Cancer Screening — 23-Year Follow-up
A 13% reduction in mortality was observed in the screening group, with an improved harm-benefit ratio. For every 456 men screened, one prostate cancer death was prevented. It is an easy and inexpensive test, though concerns remain regarding unnecessary biopsies and overtreatment.
Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase I Study
Pasritamig was administered to patients who had received a median of four prior lines of systemic therapy. It was well tolerated, with manageable adverse events, making it suitable for outpatient administration. The treatment showed a median radiographic progression-free survival of 7.85 months, and 14 out of 33 participants achieved a ≥50% reduction in baseline PSA levels. So, stay tuned.