Purpose of review

Active surveillance is a management strategy for early-stage prostate cancer designed to balance early detection of aggressive disease and overtreatment of indolent disease. We evaluate recently reported outcomes and discuss the potentially most important endpoints for such an approach.

Recent findings

The past 2 years have seen the publication of two trials of watchful waiting versus immediate treatment and updates of multiple active surveillance cohorts for men with early-stage prostate cancer. The watchful waiting trials demonstrated a small potential mortality benefit to immediate treatment when applied to all risk levels (6% absolute difference at 15 years), emphasizing the importance of a risk-adapted strategy. In reported active surveillance cohorts, prostate cancer death and metastasis remain rare events. Intermediate outcomes such as progression to treatment and upgrading/upstaging on final disease appear consistent among cohorts, but must be interpreted with caution when compared with historical controls of immediate treatment because of potential selection bias.

Summary

The safety of active surveillance has been reinforced by recent reports. Accumulation of additional data on men with intermediate risk cancer and development and validation of new biomarkers of risk will allow refined and, likely, expanded use of this approach.

Purpose of review

Over the past several years, multiple biomarkers designed to improve prostate cancer risk stratification have become commercially available, while others are still being developed. In this review, we focus on the evidence supporting recently reported biomarkers, with a focus on gene expression signatures.

Recent findings

Many recently developed biomarkers are able to improve upon traditional risk assessment at nearly all stages of disease. Prominent examples are reviewed in this article. ConfirmMDx uses gene methylation patterns to improve detection of clinically significant cancer following negative biopsy. Both the Prolaris and Oncotype DX Genomic Prostate Score tests can improve risk stratification following biopsy, especially among men who are eligible for active surveillance. Prolaris and the Decipher genomic classifier have been associated with risk of adverse outcome following prostatectomy, while Oncotype DX is being studied in this setting. Finally, recent reports of the association of androgen receptor-V7 in circulating tumor cells with resistance to enzalutamide and abiraterone raise the possibility of extending the use of genetic biomarkers to advanced disease.

Summary

With the development of multiple genetic expression panels in prostate cancer, careful study and validation of these tests and integration into clinical practice will be critical to realizing the potential of these tools.

Background

Biopsy progression on active surveillance (AS) for prostate cancer (PCa) often reflects failure of the initial biopsy to detect cancer present at enrollment. The risks for delayed treatment among men who progress on AS are not well defined.

Objective

To report outcomes for men who underwent surgery after AS compared to men who underwent immediate surgery and the influence of selection bias on this outcome.

Design, setting, and participants

AS-eligible (ASE) men who underwent radical prostatectomy (RP) after a median of 20 mo of AS were compared to ASE men who underwent RP within 6 mo of diagnosis. A subset of men on AS who underwent RP after upgrade to Gleason 3+4 was compared to matched controls with similar pretreatment biopsy features who underwent immediate RP.

Outcome measurement and statistical analysis

Rates of adverse pathology (upstaging, positive surgical margin, or Gleason upgrading) were examined. Logistic regression was used to determine associations between treatment subgroup and adverse pathology.

Results and limitations

Of 157 ASE men who underwent delayed RP after AS, 54 were upgraded to Gleason 3+4 before surgery. ASE men who underwent immediate RP had lower probability of adverse pathology than ASE men who underwent delayed RP (hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.21-0.55). The rate of adverse pathology did not differ between immediate and delayed RP patients matched for pretreatment characteristics (HR 0.79, 95% CI 0.27-2.28). The observational design of this study is its main limitation.

Conclusions

When compared to men with similar pretreatment biopsy features, those who underwent delayed RP were not at higher risk of adverse pathology.

Patient summary

The oncologic safety of delayed treatment when indicated for men enrolled in active surveillance for prostate cancer is important. We found that men who underwent delayed surgery had similar outcomes to men who underwent immediate prostatectomy.

Purpose

Active surveillance to manage prostate cancer provides an alternative to immediate treatment in men with low risk prostate cancer. We report updated outcomes from a long-standing active surveillance cohort and factors associated with reclassification.

Materials and methods

We retrospectively reviewed data on all men enrolled in the active surveillance cohort at our institution with at least 6 months of followup between 1990 and 2013. Surveillance consisted of quarterly prostate specific antigen testing, repeat imaging with transrectal ultrasound at provider discretion and periodic repeat prostate biopsies. Factors associated with repeat biopsy reclassification and local treatment were determined by multivariate Cox proportional hazards regression. We also analyzed the association of prostate specific antigen density and outcomes stratified by prostate size.

Results

A total of 810 men who consented to participate in the research cohort were followed on active surveillance for a median of 60 months. Of these men 556 (69%) met strict criteria for active surveillance. Five-year overall survival was 98%, treatment-free survival was 60% and biopsy reclassification-free survival was 40%. There were no prostate cancer related deaths. On multivariate analysis prostate specific antigen density was positively associated with the risk of biopsy reclassification and treatment while the number of biopsies and time between biopsies were inversely associated with the 2 outcomes (each p <0.01). When stratified by prostate volume, prostate specific antigen density remained significantly associated with biopsy reclassification for all strata but prostate specific antigen density was only significantly associated with treatment in men with a smaller prostate.

Conclusions

Significant prostate cancer related morbidity and mortality remained rare at intermediate followup. Prostate specific antigen density was independently associated with biopsy reclassification and treatment while on active surveillance.