Editorial

Prospective Validation of Active Surveillance in Prostate Cancer: The PRIAS Study

Only 1 randomized controlled trial has compared focal therapy and active surveillance (AS) for the low-risk prostate cancer (PCa). We investigated whether focal HIFU (fHIFU) yields oncologic advantages over AS for low-risk PCa.

We included 2 non-randomized prospective series of 132 (fHIFU) and 421 (AS) consecutive patients diagnosed with ISUP 1 PCa between 2008 and 2018. A matched pair analysis was performed to decrease potential bias. Study main outcomes were freedom from radical treatment (RT) or androgen-deprivation therapy (ADT), treatment-free survival (TFS), time to metastasis, and overall survival (OS).

Median fHIFU follow-up was 50 months (interquartile range, 29-84 months). Among matched variables, no major differences were recorded except for AS having more suspicious digital rectal examination findings (P = .0074) and recent enrollment year (P = .0005). Five-year intervention-free survival from RT or ADT was higher for the fHIFU cohort (67.4% vs. 53.8%; P = .0158). Time to treatment was approximately 10 months shorter for AS than for fHIFU (time to RT, P = .0363; time to RT or ADT, P = .0156; time to any treatment, P = .0319). No differences were found in any-TFS (fHIFU, 61.4% vs. AS, 53.8%; P = .2635), OS (fHIFU, 97% vs. AS, 97%; P = .9237), or metastasis (n = 0 in fHIFU and n = 2 in AS; P = .4981). Major complications (≥ Clavien 3) were rare (n = 4), although 36.4% of men experienced complications. No relevant changes were noted in continence (P = .3949).

At a 4-year median follow-up, fHIFU for mainly low-risk PCa (ISUP grade 1) is safe, may decrease the need for radical treatment or ADT and may allow longer time to treatment compared to AS. Nonetheless, no advantages are seen in PCa progression and/or death (OS).

To date, only one trial compared focal therapy and active surveillance (AS) for low-risk prostate cancer (PCa). In addition, long-term outcomes of focal cryotherapy (FC) are lacking.

Our aim was to evaluate long-term outcomes of FC and compare them with AS.

We included two prospective series of 121 (FC) and 459 (AS) consecutive patients (2008–2018) for low- to intermediate-risk PCa.

Study outcomes were radical therapy–free or androgen deprivation therapy (ADT)-free, any treatment-free, metastasis-free, and overall survival. A matched pair analysis was performed using seven covariates.

The median FC follow-up was 85 mo (interquartile range 58–104); 92 (76%) men had International Society of Urological Pathology (ISUP) grade 1. Among matched variables, no significant differences were present except for cT stage and year of entry (both p < 0.01). Ten-year radical therapy–free or ADT-free, any treatment-free, metastasis-free, and overall survival were 51%, 40.2%, 93.9%, and 97%, respectively for FC. No differences were noted with AS (all p > 0.05), with the exception of time to radical therapy, time to radical therapy and ADT, and time to any treatment, all being shorter for AS (all p < 0.01). Freedom from radical treatment or ADT was higher for FC (AS 10 yr 39.3%; p = 0.04). Complications were relatively rare (26.5%) and mainly of low grade (Clavien >2, n = 3); three men developed incontinence (p = 0.0814), while both International Index of Erectile Function 5 and International Prostate Symptom Score scores increased (p = 0.0287 and p = 0.0165, respectively). Limitations include absence of randomization.

At an early long-term follow-up, FC in the context of mainly low-risk PCa is safe and increases time to radical therapy but does not provide meaningful oncological advantages compared with AS.

We compared focal cryotherapy with active surveillance mainly for low-risk prostate cancer. Focal cryotherapy, despite having fewer complications, did not yield meaningful advantages over active surveillance at 10 yr. Active surveillance should be preferred to focal cryotherapy for these patients.

Active surveillance (AS) is the preferred option for initial management for low-risk prostate cancer (PC). Although many AS protocols exist, there is little evidence to support one over another.

To assess whether there is difference in overall (OS), prostate cancer–specific (CSS), metastasis-free (MFS), or treatment-free (TFS) survival between a strict (Prostate cancer Research International: Active Surveillance [PRIAS]) and a loose (European Randomized study of Screening for Prostate Cancer [ERSPC]) AS protocol.

This study included two cohorts of men (n = 518) with low-risk, localized, Gleason score ≤7 PC. The ERSPC cohort included 241 men followed for 9.5 yr (median) with a non–protocol-based follow-up. The PRIAS cohort included 277 men followed for 5 yr (median) with a strict protocol.

OS, CSS, MFS, and TFS were compared by the Kaplan-Meier method, competing risk analysis, and Cox proportional hazard regression.

As expected, due to the difference in median follow-up time between the cohorts, a difference in the absolute number of events was seen. However, no difference in any of the survival outcomes was evident in the Kaplan-Meier or competing risks analysis. Furthermore, in Cox proportional hazard regression analysis, cohort (ERSPC vs PRIAS) was not associated with any of the outcomes. Results are limited by the retrospective study design, limited statistical power, and inability to match the cohorts for predictive factors.

There was no difference in survival outcomes between a non–protocol-based follow-up and a protocol-based contemporary AS follow-up of patients with low-risk PC. However, a longer follow-up is needed.

We compared survival outcomes of two cohorts of patients with low-risk prostate cancer: a strict and a loose follow-up protocol. We found no differences in survival measures between the cohorts.

Background

Currently, interpretation of prostate MRI is performed qualitatively. Quantitative assessment of the mean apparent diffusion coefficient (mADC) is promising to improve diagnostic accuracy while radiomic machine learning (RML) allows to probe complex parameter spaces to identify the most promising multi-parametric models. We have previously developed quantitative RML and ADC classifiers for prediction of clinically significant prostate cancer (sPC) from prostate MRI, however these have not been combined with radiologist PI-RADS assessment.

Purpose

To propose and evaluate diagnostic algorithms combining quantitative ADC or RML and qualitative PI-RADS assessment for prediction of sPC.

Methods and population

The previously published quantitative models (RML and mADC) were utilized to construct four algorithms: 1) Down(ADC) and 2) Down(RML): clinically detected PI-RADS positive prostate lesions (defined as either PI-RADS≥3 or ≥4) were downgraded to MRI negative upon negative quantitative assessment; and 3) Up(ADC) and 4) Up(RML): MRI-negative lesions were upgraded to MRI-positive upon positive assessment of quantitative parameters. Analyses were performed at the individual lesion level and the patient level in 133 consecutive patients with suspicion for clinically significant prostate cancer (sPC, International Society of Urological Pathology (ISUP) grade group≥2), the test set subcohort of a previously published patient population. McNemar test was used to compare differences in sensitivity, specificity and accuracy. Differences between lesions of different prostate zones were assessed using ANOVA. Reduction in false positive assessments was assessed as ratios.

Results

Compared to clinical assessment at the PI-RADS≥4 cut-off alone, algorithms Down(ADC/RML) improved specificity from 43% to 65% (p = 0.001)/62% (p = 0.003), while sensitivity did not change significantly at 89% compared to 87% (p = 1.0)/89% (unchanged) on the patient level. Reduction of false positive lesions was 50% [26/52] in the PZ and 53% [15/28] in the TZ. Algorithms Up(ADC/RML) led, on a patient basis, to an unfavorable loss of specificity from 43% to 30% (p = 0.039)/32% (p = 0.106), with insignificant increase of sensitivity from 89% to 96%/96% (both p = 1.0). Compared to clinical assessment at the PI-RADS≥3 cut-off alone, similar results were observed for Down(ADC) with significantly increased specificity from 2% to 23% (p < 0.001) and unchanged sensitivity on the lesion level; patient level specificity increased only non-significantly.

Conclusion

Downgrading PI-RADS≥3 and ≥ 4 lesions based on quantitative mADC measurements or RML classifiers can increase diagnostic accuracy by enhancing specificity and preserving sensitivity for detection of sPC and reduce false positives.