The first paper was by Deka et al. “Association Between African American Race and Clinical Outcomes in Men Treated for Low-Risk Prostate Cancer with Active Surveillance” published in the Journal of the American Medical Association (JAMA).1 Dr. Salari notes that there has been lower uptake of active surveillance among Black men, potentially leading to an increased burden of treatment-related side-effects. As we learn more about active surveillance, it is important to ensure that all members of the population are able to take advantage of the benefits of active surveillance. This study was a retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The main outcomes of this study were progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality. This study included 8,726 men, of which 2,280 were African American men (26.1%; median age, 63.2 years) and 6,446 were non-Hispanic White men (73.9%; median age, 65.5 years), with a median follow-up of 7.6 years (IQR 5.7-9.9). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence:
- Of disease progression was 59.9% for African American versus 48.3% non-Hispanic white men (difference 11.6%, 95% confidence interval [CI] 9.2% to 13.9%)
- Of receipt of definitive treatment was 54.8% for African American versus 41.4% non-Hispanic white men (difference 13.4%, 95% CI 11.0% to 15.7%)
- Of metastasis was 1.5% for African American versus 1.4% non-Hispanic white men (difference 0.1%, 95% CI -0.4% to 0.6%)
- Of prostate cancer-specific mortality was 1.1% for African American versus 1.0% non-Hispanic white men (difference 0.1%, 95% CI -0.4% to 0.6%)
- Of all-cause mortality for 22.4% African American versus 23.5% non-Hispanic white men (difference 1.1%, 95% CI -0.9% to 3.1%)
Dr. Salari provided the following conclusions and take-away messages from this study:
- In the equal access Veterans Health Administration (VHA) health care setting, Black men compared with white men had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment
- However, similar (and low) rates of metastasis and mortality were observed
- Active surveillance can be safe and effective for Black men, as >40% of Black men with low-risk prostate cancer were able to avoid treatment for 10 years
- There were several limitations to this study, including no specific follow-up protocol for active surveillance, this study was done in the pre-MRI era, and the VHA health care setting may limit the generalizability of these findings and highlights the importance of access to high-quality and close follow-up
- Longer-term follow-up is needed to better assess mortality risk
The second paper discussed by Dr. Salari was by Schenk et al. “African American Race is Not Associated with Risk of Reclassification during Active Surveillance: Results from the Canary Prostate Cancer Active Surveillance Study” published in The Journal of Urology.2 The Canary PASS (Prostate Active Surveillance Study) is a protocol-driven, active surveillance cohort with a prespecified prostate-specific antigen (PSA) and surveillance biopsy regimen. Men included in this study had Gleason Grade Group 1 or 2 disease at diagnosis and fewer than 5 years between diagnosis and enrollment, and had undergone 1 or more surveillance biopsies. The reclassification risk, defined as an increase in the Gleason score on subsequent biopsy, was compared between African American and Caucasian American men using Cox proportional hazards models. There were 1,315 men included in this study of which 89 (7%) were African American and 1,226 (93%) were Caucasian. There was no difference in the treatment rate in African American and Caucasian men. Additionally, African American race was not associated with risk of reclassification (hazard ratio [HR] 1.16, 95% CI 0.78-1.72):
Of the 441 men who underwent radical prostatectomy after a period of active surveillance, the rate of adverse pathology was similar in those who were African American and Caucasian (46% vs. 47%, p=0.99).
Dr. Salari provided the following conclusions and take-aways from this study:
- In this prospective cohort study of men on active surveillance who followed a standardized protocol of regular PSA testing and biopsy, no difference in risk of reclassification was seen between Black and white men
- There was no higher risk of adverse pathology among a subset of men that eventually underwent radical prostatectomy
- This data supports the use of a standardized active surveillance protocol among Black men with favorable-risk prostate cancer
- Limitations of this study include the modest sample size of Black men (n=89) and relatively short follow-up time (median 3.9 years)
The optimal timing of radiation therapy after radical prostatectomy is still unclear. Previous randomized controlled trials (RCT) showed improved biochemical control with adjuvant radiotherapy compared to observation, but inconsistent results regarding long-term outcomes of progression-free survival (PFS), metastasis-free survival (MFS), and overall survival (OS). In 2020, there was the publication of long-awaited results from three RCTs plus a pre-planned meta-analysis comparing adjuvant radiotherapy to early salvage radiotherapy in cases of PSA progression. The final paper discussed by Dr. Salari was by Vale et al. “Adjuvant or early salvage radiotherapy for the treatment of localized and locally advanced prostate cancer: A prospectively planned systematic review and meta-analysis of aggregate data” published in The Lancet3 – a meta-analysis of these three trials. There were 2,153 patients recruited between November 2007 and December 2016, with a median follow-up ranging from 60 months to 78 months, with a maximum follow-up of 132 months. A total of 1,075 patients were randomly assigned to receive adjuvant radiotherapy and 1,078 to early salvage radiotherapy, of whom 421 (39.1%) had commenced treatment at the time of analysis. Based on 270 events, the meta-analysis showed no evidence that event-free survival was improved with adjuvant radiotherapy compared with early salvage radiotherapy (HR 0.95, 95% CI 0.75-1.21), with only a 1 percentage point (95% CI -2 to 3) change in 5-year event-free survival (89% vs. 88%):
These three trials and the meta-analysis suggest that adjuvant radiotherapy does not improve event-free survival in men with localized or locally advanced prostate cancer.
Dr. Salari provided the following conclusions and summary remarks from the ARTISTIC study:
- There is no evidence that adjuvant radiotherapy improved event-free survival compared with early salvage radiotherapy
- While event-free survival is not a surrogate for MFS, trials of prostate cancer radiotherapy typically show a greater effect on short-term events like biochemical control than long-term outcomes, therefore it is unlikely that a benefit in MFS will emerge
- This data supports the use of early salvage radiotherapy as a standard of care, as it results in similar biochemical control to adjuvant radiotherapy and spares over half of men pelvic radiation and the associated GU/GI toxicities
Written by: Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
1. Deka, Rishi, P. Travis Courtney, J. Kellogg Parsons, Tyler J. Nelson, Vinit Nalawade, Elaine Luterstein, Daniel R. Cherry et al. "Association Between African American Race and Clinical Outcomes in Men Treated for Low-Risk Prostate Cancer With Active Surveillance." Jama 324, no. 17 (2020): 1747-1754.
2. Schenk, Jeannette M., Lisa F. Newcomb, Yingye Zheng, Anna V. Faino, Kehao Zhu, Yaw A. Nyame, James D. Brooks et al. "African American race is not associated with risk of reclassification during active surveillance: results from the Canary Prostate Cancer Active Surveillance Study." The Journal of urology 203, no. 4 (2020): 727-733.
3. Vale, Claire L., David Fisher, Andrew Kneebone, Christopher Parker, Maria Pearse, Pierre Richaud, Paul Sargos et al. "Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data." The Lancet (2020).