Many men with low-risk prostate cancer switch from active surveillance to active treatment
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Use of active surveillance for low-risk prostate cancer increased significantly over time, but a relatively high rate of men switched to definitive treatment within 5 years, according to a population-based study in The Journal of Urology.
“These results may help guide policymaking, developing quality indicators, and developing targeted continued education for physician and patients embarking on [active surveillance] to establish realistic expectations,” Narhari Timilshina, PhD candidate in the department of medicine at University Health Network and at Institute of Health Policy, Management and Evaluation at University of Toronto, and colleagues wrote.
The analysis included 16,852 men diagnosed with low-risk (Gleason score 6/grade group 1) prostate cancer between 2008 and 2014 in Ontario, Canada. Among them, 51% (median age, 63.9 years) underwent active surveillance as initial management, 36% (median age, 62.4 years) received initial treatment and 13% (median age, 72.9 years) underwent watchful waiting.
All men in the active surveillance cohort had confirmatory biopsies within 2 years after their diagnosis biopsy.
Researchers defined discontinuation of active surveillance as receipt of any definitive intervention or treatment with primary androgen deprivation therapy. They followed patients from the date of diagnosis until the start of definitive treatment, loss to follow-up, death, metastatic progression or data lock period (Dec. 31, 2017), whichever came first.
Results showed use of active surveillance increased from 38% in 2008 to 69% in 2014.
However, after median follow-up of 48 months, more than half of men (50.8%) discontinued active surveillance, mostly because of tumor progression. Cumulative probability of remaining on active surveillance declined from 85.2% at 1 year to 58% at 3 years and 52.4% at 5 years.
After initial active surveillance, median time to definitive treatment was 16 months (IQR, 11-25 months).
“Factors associated with active surveillance discontinuation were younger age at diagnosis, year of diagnosis, higher comorbidities, treatment at academic center, treatment by physician and institution in the highest volume tertile, and adverse cancer-specific characteristics (higher prostate specific antigen [PSA], higher number of positive cores and higher percentage of core involvement at diagnosis),” researchers wrote.
About half of men (52%) on initial active surveillance went on to receive radical prostatectomy, whereas 34% received radiotherapy with ADT, 6% received radiotherapy alone and 4.7% received ADT alone.
Researchers noted several study limitations, which included an inability to confirm the intent of active surveillance compared with watchful waiting or to account for PSA progression, psychological characteristics, quality of life or symptomatic progression, all of which could influence discontinuation.
“Based on our results, there is a significant rate of pathological progression, in particular grade progression, that drives discontinuation of active surveillance,” researchers wrote.
They noted the importance of the results for men with prostate cancer, their providers and policymakers.
“There is a dire need to develop robust tests such as biomarkers and advanced imaging to move the field beyond nonspecific measures (ie, PSA) and invasive prostate biopsy,” Timilshina and colleagues wrote. “Competing health risks and patient characteristics should be combined with disease-specific traits to better select patients for inclusion. The practice would benefit from the development of quality indicators, targeted continuing education for physicians, and patient education with shared decision-making at the onset of active surveillance.”
Perspective
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Andres F. Correa, MD
Timilshina and colleagues should be congratulated for reporting this real-world analysis on the use of active surveillance for men with low-risk prostate cancer and shining some light into identifiable factors associated with active surveillance discontinuation. That being said, the use of registry data and definition of active surveillance are significant limitations of the study.
The reason for discontinuation is unknown for approximately one-third (28.9%) of men, and that is a significant confounder of the results. Moreover, the researchers’ definition of active surveillance may include men who were considered for active surveillance but not active surveillance candidates because they were upgraded to Gleason group 2 disease after confirmation biopsy, explaining the significant drop-off between 1 and 3 years. Using a more stringent definition of active surveillance would have teased this potential confounder and allowed a more appropriate population to be analyzed.
The study does show the importance of the treating physician in the decision to continue active surveillance for management of low-risk prostate cancer. This finding confirms a Michigan Urological Society Improvement Collaborative cooperative study by Auffenberg and colleagues, which demonstrated that the most important factor associated with selection and continuation of active surveillance is the physician, regardless of clinical and patient-related factors.
Reference:
Auffenberg GB, et al. JAMA Surg. 2017;doi:10.1001/jamasurg.2017.1586.
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