Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.
Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.
Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.
SAN FRANCISCO — Men with prostate cancer who are on active surveillance may be overtreated if their clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw told attendees of a symposium on genitourinary cancers.
In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.
Dr. Loblaw said that research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer. This surveillance typically entails some type of PSA monitoring, with the decision to initiate treatment often based on a PSA trigger, said the radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.
The investigators therefore tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of progression after a median of 6.8 years (7.2 years for survivors).
At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.
“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.
The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).
The rate was intermediate for a PSA threshold of 10 ng/mL (38%); first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%); linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%); overall PSA velocity of greater than 2 ng/mL per year (42%); and a 1-year PSA velocity of greater than 2 ng/mL (51%).
The findings suggest that only a 20-ng/mL threshold has a low false-trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, he said.
My Take
Active Surveillance May Not Catch On
Active surveillance is a hot topic. More and more men with low-risk disease are being diagnosed with prostate cancer in the United States and around the world. Many of these men would be candidates for active surveillance. In real-world practice, however, many questions remain about offering active surveillance to men with localized prostate cancer, including these:
▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?
▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?
▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment for a patient with localized prostate cancer?
In their study of 315 men, the researchers found that a PSA threshold of 20 ng/mL had the lowest false-trigger rate for men on active surveillance. In other words, by allowing the PSA to go above 20 before offering active treatment, the authors suggested that this PSA threshold may be the most appropriate marker for switching from active surveillance to active treatment.
Although I applaud the researchers for doing this work, many patients would be very uncomfortable allowing their PSA to go as high as 20 before considering a repeat biopsy or treatment. In the D'Amico risk stratification scheme in localized prostate cancer, men with a PSA rated at 20 have high-risk disease. Therefore, if we allow a PSA to go above 20 in men on active surveillance before we recommend active treatment, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients alike.