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Review: Active Surveillance for Intermediate-risk Prostate Cancer

Key findings

  • Only a minority of patients with intermediate-risk (IR) prostate cancer are managed with active surveillance (AS), largely because of uncertainty about appropriate indications
  • This narrative review found that definitions of IR prostate cancer, definitions of favorable and unfavorable disease, and recommendations about the use of AS vary among the four major sets of guidelines for managing localized prostate cancer
  • Some major guidelines recommend observation or watchful waiting based on life expectancy; watchful waiting is not a synonym for AS
  • Mass General Brigham researchers are developing a machine-learning model that will hopefully allow robust prediction of outcomes in patients with IR prostate cancer

The use of active surveillance (AS) to manage intermediate-risk (IR) prostate cancer has gradually increased over time. Still, only a minority of patients are managed with this approach, mainly because of uncertainty about its safety.

Physicians at Mass General Brigham recently published a narrative review about that uncertainty in the World Journal of Urology. The authors are Madhur Nayan, MDCM, PhD, a fellow in the Department of Urology at Massachusetts General Hospital, Adam S. Feldman, MD, MPH, director of research and a urologic oncologist in the department, and Filipe L. F. Carvalho, MD, PhD, a fellow in the Division of Urology at Brigham and Women's Hospital.

Varying Definitions

Part of the ambiguity about whether AS is appropriate for IR prostate cancer is attributable to the lack of uniformity in definitions of IR disease.

There are four major sets of guidelines for managing localized prostate cancer that contain four different definitions:

The Cancer of the Prostate Risk Assessment (CAPRA) score involves the fifth definition.

In some guidelines, IR disease is further stratified as favorable or unfavorable, and definitions of those statuses, too, vary across guidelines.

Recommendations for AS

The AUA/ASTRO/SUO, CUA, EAU, and NCCN guidelines also differ with respect to their recommendations about when to use AS in IR prostate cancer.

Guidelines that recognize favorable IR agree AS can be considered for those patients, but they also caution that the evidence supporting that recommendation is weak. When AS is chosen, there is limited evidence to guide its intensity or when to transition to observation.

The reviewers discuss in detail the limitations in interpreting observational studies and the lack of contemporary randomized controlled trials to guide practice.

AS is not cited in any of the major guidelines as an option for unfavorable IR prostate cancer. In fact, outcomes of AS are significantly worse for these patients.

Recommendations for Watchful Waiting

AS is not a synonym for watchful waiting:

  • AS means actively monitoring the course of disease with the intent to provide curative therapy if cancer progresses
  • Watchful waiting refers to a decision to forego local therapy for curative intent and instead monitor the course of the disease, with the possibility of starting primary androgen deprivation and/or palliative treatment if progression occurs

The AUA/ASTRO/SUO guidelines suggest observation or watchful waiting if life expectancy is ≤5 years; the NCCN guidelines suggest observation if life expectancy is ≤10 years. These recommendations based on life expectancy imply that in elderly patients and those with multiple comorbidities, the benefit of actively monitoring favorable IR disease does not outweigh the competing risks of death.

Risk Stratification

Prostate cancer that is grade group 3 (International Society of Urological Pathology) is known to warrant timely intervention, but there is uncertainty about when AS is appropriate for grade group 2 disease. Several disease characteristics have been proposed to risk-stratify these patients, including prostate-specific antigen, PSA density, clinical stage (cT2 vs T1), percentage of core involvement, perineural invasion, Black race, certain MRI features, and genomic classifiers.

A combination of clinical, pathological, imaging, and genetic information will likely prove to be more useful than any single criterion. Mass General Brigham researchers are using a diverse multi-institutional cohort to develop a machine-learning model for robust prediction of outcomes in patients with IR prostate cancer. These predictions will be validated in a subsequent randomized trial.

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Madhur Nayan, MDCM, PhD, and Adam S. Feldman, MD, MPH, and colleagues created the first machine learning models for predicting prostate cancer progression during active surveillance and found they outperformed traditional logistic regression.


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