While the uptake of active surveillance (AS) for low-risk prostate cancer has increased over time, about half of patients eventually discontinue this strategy, according to an observational Canadian population-based study.

The use of AS increased from 38% in 2008 to 69% in 2014; however, over this study period, 50.8% of patients discontinued AS and proceeded to definitive treatment, reported Antonio Finelli, MD, MSc, of the University of Toronto, and colleagues in the Journal of Urology.

The majority of patients transitioning to definitive treatment did so for pathological reasons — grade progression in 51.5% and volume progression in 8.5% — while 11.1% went on to definitive treatment without progression.

Factors associated with transitioning to definitive treatment included younger age, care provided by high-volume physicians and institutions, and higher prostate-specific antigen (PSA) levels and greater prostate cancer volume at the time of diagnosis.

Treatment-free survival with AS was 85% at 1 year, 63% at 2 years, 58% at 3 years, 55% at 4 years, and 52% at 5 years.

“These results may help guide policy making, developing quality indicators, and developing targeted continued education for physicians and patients embarking on AS to establish realistic expectations,” Finelli and team wrote.

While AS has become the standard of care for patients with low-risk prostate cancer, the authors noted that there are limited real-world data on discontinuation rates outside of academic centers, despite the fact that most patients with low-risk disease are treated in community settings.

In an editorial comment accompanying the study, Michael S. Sessine, MD, and Jeffrey J. Tosoian, MD, MPH, both of the University of Michigan in Ann Arbor, noted that the 5-year treatment-free survival rate in the current study population was below the rates reported by prospective AS programs at Sunnybrook Health in Toronto and Johns Hopkins Medicine in Baltimore.

They pointed out that these programs showed an increase in the proportion of patients remaining on AS over time, which was “likely the result of better initial patient selection (i.e., less undersampling), with more patients exposed to MRI and targeted biopsies during diagnostic and confirmatory testing.” They suggested that the lower treatment-free survival rate in the current study could be attributed to initial undersampling.

“While 51.5% of patients underwent treatment following grade progression, the reason for treatment was unknown in nearly 30%, making it difficult to know with certainty the root of these differences,” wrote Sessine and Tosoian. Regardless, the new findings “have added to the growing body of AS literature and provided potential risk factors for treatment that can be used to better educate and counsel patients initiating AS.”

For this study, Finelli and coauthors used health databases from Ontario and identified 20,745 men diagnosed with low-risk prostate cancer from January 2008 through December 2014. The final study cohort consisted of 16,852 patients, 51% of whom were managed by AS, 36% with initial treatment, and 13% with watchful waiting.

Patients were followed from the date of their diagnosis until the start of definitive treatment, loss to follow-up, death, metastatic progression, or data lock (Dec. 31, 2017).

Of the men who went on to receive definitive treatment after AS, 52% underwent radical prostatectomy, 34% received radiotherapy with androgen deprivation therapy (ADT), 6.0% received radiotherapy alone, 4.7% were managed with ADT alone, and 2.7% underwent radical prostatectomy and ADT. The median time to definitive treatment after initial AS was 16 months.

On multivariable analysis, factors associated with AS discontinuation were:

• Younger age at diagnosis
• Year of diagnosis
• More comorbidities
• Treatment at an academic center versus non-academic center
• Treatment by a radiation oncologist versus a urologist
• Treatment by higher-volume physicians and/or institutions
• Disease characteristics such as higher PSA level, higher positive cores, and higher maximum percentage core involvement at diagnosis