Original article
Identifying intermediate-risk candidates for active surveillance of prostate cancer

https://doi.org/10.1016/j.urolonc.2017.06.048Get rights and content

Highlights

  • A total of 144 patients with IR prostate cancer followed by active surveillance for a median of 4.5 years.

  • AS maintained in 50% of Intermediate-risk group at 5 years.

  • Treatment rates were significantly lower for VLR group compared to LR or IR group.

  • In the IR group, percentage of biopsy cores involved was an independent predictor of who would cease AS.

Abstract

Purpose

Although already established for very-low and low-risk (LR) prostate cancer (PCa), controversy remains around offering active surveillance (AS) to men with intermediate-risk (IR) PCa. As IR represents a broad spectrum of disease biology, there is a critical need to define eligibility criteria that will enable both patient and physician to accept AS as the best balance of competing risks. In this study, we aimed to identify predictors of progression to enable optimal patient selection.

Materials and methods

In our AS cohort, men were assigned to risk categories according to the National Comprehensive Cancer Network (NCCN favorable and NCCN unfavorable) and the CAPRA classifications. Clinical, biochemical and pathological characteristics, progression to definitive invasive treatment, and pathologic progression on follow-up biopsies were compared among these groups. A multivariate Cox regression model was used to identify independent predictors of progression on AS.

Results

AS was the initial management option for 651 men, including 144 with IR PCa. During the median follow-up of 4.5 years (range: 0.6–19.1), 259 patients (39.7%) underwent definitive treatment. Further, 5- and 10-year predicted rates of intervention for IR patients were 50% and 66%, respectively. Treatment rates were no different between the NCCN LR and NCCN IR groups, but were higher in CAPRA IR compared to CAPRA LR groups (P = 0.025). NCCN unfavorable IR patients had a twofold increased risk of definitive intervention compared to favorable IR (hazard ratio [HR] = 2.07; 95% CI: 1.17–3.65; P = 0.01). In the entire cohort, the percentage of biopsy cores positive (continuous variable; P = 0.006) and ISUP grade 2 or higher on initial biopsy (P = 0.027) were independent predictors of cessation of AS on multivariate analysis. In the intermediate group, only the percentage of positive biopsy cores was an independent predictor (P = 0.021) of AS cessation. Only 1 IR patient developed metastatic disease (0.7%). Actuarial overall survival at 5 and 10 years was 98.6% and 94.1%, respectively. There were 2 PCa deaths at 18.7 and 19.1 years of follow-up.

Conclusion

In all AS, increasing percentage of core involvement and presence of Gleason pattern 4 are predictors of increased risk of progression. For IR patients, the NCCN favorable criteria and CAPRA score predict those more likely to remain on AS.

Introduction

Active surveillance (AS) is widely recommended as a standard initial management option for men diagnosed with very low and low risk (LR), apparently localized prostate cancer (PCa) [1], [2], [3]. Its role in IR PCa [4], [5], [6] remains controversial, and many clinicians believe that all IR cases should be managed early because of an increased risk of metastatic disease, despite the fact that in many cases AS avoids overtreatment and associated morbidity [7], [8]. However, the PIVOT trial demonstrated that for men treated with radical prostatectomy for IR, screen detected PCa had no overall survival advantage compared to men treated with observation alone, suggesting the feasibility of a modern surveillance protocol in this patient group as well [9].

In this retrospective review, we describe our 21-year experience with AS in a cohort of men with very low-, low-, or intermediate-risk (IR) PCa managed in a tertiary referral center. We hypothesize that some men with IR disease can be safely monitored with AS if they are carefully selected . We have offered AS to men with IR disease with the knowledge that some will prove to have clinically insignificant cancers, whereas others with more aggressive disease will be uncovered and are only deferring therapeutic intervention for a period of time. In our series, we have analyzed the use of National Comprehensive Cancer Network (NCCN) favorable/unfavorable risk criteria and CAPRA score, as well as clinical, biochemical, and pathological parameters as predictors of progression in LR and IR candidates.

Section snippets

Data source and patient selection

Since 1993, men with clinically localized PCa have been offered AS at the Vancouver Prostate Centre (VPC). Their clinical data have been collected in an Institutional Review Board–approved, prospectively accrued database. Men have been followed with a well-defined protocol including digital rectal examination and prostate-specific antigen (PSA) measurements every 6 months, restaging confirmatory transrectal ultrasound (TRUS)–guided prostate biopsy within 18 months of first diagnosis and

Results

The clinical and pathological characteristics of the 651 patients meeting inclusion criteria are shown in Table 1. Mean age and PSA at diagnosis were 64.3 years and 5.7 ng/ml, respectively. Median follow-up for all groups was 4.5 years, with a range of 0.6 to 19.1 years (Table 1). More than 10-year follow-up was achieved in 54 men (8.2%) and more than 5-year follow-up in 293 men (45%).

Discussion

This study describes a 21-year experience of AS in a large cohort of patients with very low-, low- and intermediate-risk PCa. Most men with IR disease were “favorable” IR and were selected for AS because of individual priorities of sexual function and continence that outweighed the patient’s (and physician’s) concerns about the risk of imminent disease progression. Our results show extremely low rates of metastasis and PCa death in each of the very low-, low-, and intermediate-risk groups.

The

Conclusion

Parameters that predict for a lower risk of progression in patients with IR disease include the NCCN favorable IR criteria, a low CAPRA score, and a low percentage of biopsy cores involved. However, until we have a better biologically or image-based method of separating the “good actors” from the “bad actors,” the patient and physician should accept that selecting AS is better considered “AS with probable delayed intervention.” In our experience, the risks of progression to incurable PCa and

Acknowledgments

The authors would like to acknowledge the contribution of Mr. Kenny Lynch and Drs. Antonio Hurtado-Coll and Michael Peacock in data collation and resource management.

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