Active surveillance (AS) should be cautiously offered to men with intermediate-risk prostate cancer, investigators suggest.

Thenappan Chandrasekar, MD, and colleagues from Thomas Jefferson University in Philadelphia, Pennsylvania, conducted the first population-level analysis of AS, watchful waiting (WW), and active treatment (AT) for low-risk and intermediate-risk prostate cancer. Using the Surveillance, Epidemiology, and End Results (SEER) database 2010-2015, the investigators identified 166,244 men with localized Grade Group (GG) 1 or 2 disease. They were able to distinguish patients on WW versus AS using the recent SEER WW variable.

At 5 years, both cancer-specific (CSS) and overall survival (OS) appeared worse for patients with GG2 and intermediate-risk prostate cancer receiving AS compared with AT involving curative surgery or radiation therapy, Dr Chandrasekar’s team reported in Urology. Among men with GG2, the 5-year CSS was 100% in the AT group compared with 99% in the AS group, and the 5-year OS was 94% vs 88%, respectively. The investigators further stratified 94,891 patients by National Comprehensive Cancer Network (NCCN) favorable and unfavorable risk categories. Among patients with favorable intermediate-risk disease, the 5-year CSS was 100% vs 99% and the 5-year OS was 95% vs 91%, in the AT and AS groups, respectively. Among men with unfavorable intermediate-risk disease, the 5-year CSS was 100% vs 98% and the 5-year OS was 94% vs 88%, in the AT and AS groups, respectively.


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In contrast, men with GG1 prostate cancer had similar survival outcomes whether or not they received active treatment. Among the GG1 cohort, the 5-year CSS was 100% vs 100% and the 5-year OS was 95% vs 94%, in the AT vs AS group, respectively. The WW group, which included older men with comorbidities (as well as those not enrolled in AS or AT for any reason), had the worst survival outcomes across all cohorts. 

“Our analysis of a real-world, population level dataset validates the findings of smaller prospective cohorts suggesting that AS should be used cautiously in patients with reasonable life expectancy diagnosed with GG2 or [intermediate-risk prostate cancer],” Dr Chandrasekar’s team concluded. The investigators encouraged continued research to determine which subgroups of patients with intermediate-risk prostate cancer would benefit from AS. Multiparametric magnetic resonance imaging, tissue-based genetic assays, identification of germline mutations in DNA repair genes, and family history all may improve risk stratification, they noted. 

In an interview, Hiten D. Patel, MD, MPH, of Loyola University Medical Center in Maywood, Illinois, who was not involved in this study but has conducted research in this area, observed, “I still believe AS for some GG2 patients is reasonable to offer. Patients need to be informed upfront that AS for GG2 prostate cancer cannot be equated with AS for GG1, so they are taking a calculated risk. With shared decision-making, AS could still be in-line with a patient’s preferences, such as quality of life.”

In previous studies (JAMA Oncol. 2018 and J Urol. 2018), Dr Patel and colleagues showed that patients with GG2 prostate cancer in virtually all subsets have higher rates of adverse pathologic findings at surgery compared with NCCN low-risk patients. “Therefore, we would expect the same patients placed on AS would have some marginal decrease in CSS,” Dr Patel said. In the current study, the small 5-year differences in CSS between favorable and unfavorable disease could be considered “reasonable trade-offs” by some advocates of AS for intermediate-risk prostate cancer, he said.

According to Dr Patel, there may be a few clinical groups that are at lower risk for adverse outcomes on AS, including patients with a single MRI-identified prostate lesion that is biopsy-confirmed to be GG2, those with low-volume disease and a negative MRI, and patients who have less than 5% of Gleason pattern 4.

“There is still a lot of research needed in this area to set safe but useful triggers for active treatment,” he noted. “Optimal data for localized prostate cancer would require 10 to 15 years of follow-up.

“The real question for patients with GG2 prostate cancer considered for AS is how durable the management strategy is. If thresholds are set such that all patients cross over to active treatment within a few years, then perhaps the limited benefit gained from the intervention-free period will outweigh the additional costs and anxiety.”

Reference

Chandrasekar T, Bowler N, Schneider A, et al. Outcomes of active surveillance for men with intermediate risk prostate cancer: a population-based analysis. Urology. Published online June 27, 2021. doi:10.1016/j.urology.2021.05.068