Recent Research on Active Surveillance
The Risk of Being Lost to Follow-Up on AS
While active surveillance (AS) is becoming increasingly popular as a management strategy for patients diagnosed with low-risk prostate cancer, insufficient monitoring can put patients at risk for worse outcomes.
A study from the Michigan Urologic Surgery Improvement Collaborative (MUSIC), a prospective registry of patients from 44 urology practices, sought to determine rates of patients who were lost to follow- up, meaning they were not being appropriately tested for disease progression.
The study estimated that 10% of patients are lost to follow-up within two years of being on AS. Patients who were unhealthy and African-American men were more likely to be lost to follow-up. In addition, there was a wide variability in these rates among different urology practices, meaning that some clinics were monitoring patients more closely than others.
Patients who are lost to follow-up are not being appropriately monitored with routine PSA tests and repeat biopsies needed to identify whether the disease has begun to grow enough that active treatment is an appropriate next step. This puts the patient at risk for developing metastatic prostate cancer. The authors concluded, “There is ample opportunity to improve the quality of the performance as AS.”
Ginsburg KB, Auffenberg GB, Qi J, et al. Risk of Becoming Lost to Follow-up During Active Surveillance for Prostate Cancer. Eur Urol. 2018; 74(6):704–707. doi:10.1016/j.eururo.2018.08.010
Gleason Grade Reclassification in Men in AS
Patients on active surveillance should be monitored frequently to assess the growth of a patient’s prostate cancer. Grade reclassification occurs when the cancer’s Gleason grade has progressed to the next stage of Gleason scoring or Grade Group, indicating the cancer is becoming more aggressive. This is indicated by specimen examination after a repeat biopsy or a radical prostatectomy.
Two recent studies examined factors that could affect a man’s chances of having grade reclassification.
A study of more than 1,200 patients from NorthShore University HealthSystem and Johns Hopkins looked at germline genetic mutations in patients on active surveillance.
Approximately 290 patients in the study experienced grade reclassification. Patients who had BRCA1/2 mutations and ATM mutations were more likely to have grade reclassification. These findings are consistent with other research and suggest that men with these mutations are more likely to harbor aggressive prostate cancer. Considering these factors when weighing the pros and cons of treatment options, early active treatment rather than AS could be more beneficial for patients with germline BRCA1/2 mutations and ATM mutations.
Two Kinds of Genetic Mutations
Germline genetic mutations are inherited and are present in every cell in the body. Somatic mutations develop during the course of a person’s life and may only appear in cancer cells.
Carter HB, Helfand B, Mamawala M, et al. Germline Mutations in ATM and BRCA1/2 Are Associated with Grade Reclassification in Men on Active Surveillance for Prostate Cancer. Eur Urol. 2019;75(5):743–749. doi:10.1016/j.eururo.2018. 09.021
Researchers looked at data on more than 1,600 patients at Johns Hopkins from 1995-2016. They found that older age was associated with grade reclassification to Grade Group 3 or greater, which is considered aggressive prostate cancer.
The study divided men into groups by age: younger than 60, 60 to 69, and 70 years and older. Men in the oldest group had a 14% 5-year incidence rate of grade reclassification to Grade Group 3 or greater. The rates were just 4% for men younger than 60 years and 7% for men ages 60-69.
The analysis found that for each 10- year increase in age, men were more than twice as likely to be reclassified to Grade Group 3 or greater prostate cancer.
The authors wrote that these observations imply that for older men, active surveillance, rather than watchful waiting, is a more appropriate strategy.
Druskin SC, Mamawala M, Tosoian JJ, et al. Older Age Predicts Biopsy and Radical Prostatectomy Grade Reclassification to Aggressive Prostate Cancer in Men on Active Surveillance. J Urol. 2019;201(1):98–104. doi:10.1016/j.juro.2018.08.023
The Prostate Cancer Active Surveillance Project
The Summer/Fall 2019 issue of QUEST gave an in-depth report on the Prostate Cancer Active Surveillance Project’s plan to improve active surveillance protocols for men across the U.S. The research team’s proposal is currently under revision for a grant from the National Institutes of Health. Dr. Catalona is part of the PCASP’s research team.