Five-alpha reductase inhibitors in men undergoing active surveillance for prostate cancer: impact on treatment and reclassification after 6 years follow-up

92 Background: The role of 5α-reductase inhibitors (5-ARIs) in prostatic diseases remains controversial because of an FDA black box label. We have previously published on the impact of 5-ARIs in men managed with active surveillance (AS), demonstrating their protective effect against progression. However, the long-term safety of 5-ARIs in the setting of AS has never been described, thus we sought to assess this. Methods: This is a single-institution, prospectively maintained, retrospective cohort study comparing men taking a 5-ARI versus no 5-ARI while on AS for PCa. Pathologic progression was evaluated and defined as Gleason score > 6, maximum core involvement > 50%, or more than 3 cores positive on a follow-up prostate biopsy. Time dependent covariate analysis to account for time on AS but not on 5-ARI was conducted to diminish the likelihood of overestimating the benefit. To account for differences in prostate volume at baseline between 5-ARI and non-5-ARI groups sensitivity analyses were performed, restricting men in the non-5-ARI group to those with larger glands (volume > 40 ml). Kaplan-Meier analyses were conducted along with multivariable Cox proportional hazard regression modeling for predictors of pathologic progression. Results: The original cohort of 288 men on AS were analyzed. The median follow-up was 61.2 months (IQR: 29.8-95.24) with 124 men (43%) experiencing pathologic progression and 119 men (41.3%) abandoning AS. Men taking a 5-ARI experienced a lower rate of pathologic progression (24.3% vs 49.1%; p < 0.001) and were less likely to abandon AS (25.7% vs 46.3%; p = 0.002). On multivariable Cox proportional hazards analysis, lack of 5-ARI use was most strongly associated with pathologic progression (HR: 2.56; 95% confidence interval, 1.32-5.02). Sensitivity analyses done to account for gland size demonstrated that lack of 5-ARI use was still predictive of progression (HR: 2.76; CI, 1.45–5.25; p = 0.002). Importantly, 5-ARI use was not associated with increased risk of high-grade prostate cancer. Conclusions: 5-ARIs were associated with a significantly lower rate of pathologic progression and abandonment of AS in men with median follow-up of 5 years.

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A novel predictor of clinical progression in patients on active surveillance for prostate cancer

Canadian Urological Association Journal ◽

10.5489/cuaj.6122 ◽

2019 ◽

Vol 13 (8) ◽

Author(s):

Guan Hee Tan ◽

Antonio Finelli ◽

Ardalan Ahmad ◽

Marian Wettstein ◽

Alexandre Zlotta ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Cox Regression ◽

Area Under The Curve ◽

Progression Free Survival ◽

Roc Curves ◽

Standard Of Care ◽

Low Risk ◽

Clinical Progression

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PC). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP). Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and <2 years follow-up. TCLo was the number of locations with positive cores at diagnosis (DBx) and CBx. TCLo density was TCLo / prostate volume (PV). CP was progression to any active treatment while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical pathology. Independent predictors of time to CP or GP were estimated with Cox regression. Kaplan-Meier analysis compared progression-free survival curves between TCLo density groups. Test characteristics of TCLo were explored with receiver operating characteristic (ROC) curves. Results: We included 181 patients who had CBx between 2012-2015, and met inclusion criteria. The mean age of patients was 62.58 years (SD=7.13) and median follow-up was 60.9 months (IQR=23.4). A high TCLo density score (>0.05) was independently associated with time to CP (HR 4.70, 95% CI: 2.62-8.42, p<0.001), and GP (HR 3.85, 95% CI: 1.91-7.73, p<0.001). ROC curves showed TCLo density has greater area under the curve than number of positive cores at CBx in predicting progression. Conclusion: TCLo density is able to stratify patients on AS for risk of CP and GP. With further validation, it could be added to the decision-making algorithm in AS for low-risk localized PC.

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Magnetic Resonance Imaging for Tailoring the Need to Biopsy During Follow-up for Men on Active Surveillance for Prostate Cancer

European Urology ◽

10.1016/j.eururo.2021.05.024 ◽

2021 ◽

Author(s):

Anwar R. Padhani ◽

Olivier Rouvière ◽

Ivo G. Schoots

Keyword(s):

Magnetic Resonance Imaging ◽

Prostate Cancer ◽

Magnetic Resonance ◽

Active Surveillance ◽

Resonance Imaging

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Comparative performance of MRI-derived PRECISE scores and delta-radiomics models for the prediction of prostate cancer progression in patients on active surveillance

European Radiology ◽

10.1007/s00330-021-08151-x ◽

2021 ◽

Author(s):

Nikita Sushentsev ◽

Leonardo Rundo ◽

Oleg Blyuss ◽

Tatiana Nazarenko ◽

Aleksandr Suvorov ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Cancer Progression ◽

Predictive Value ◽

Machine Learning Algorithms ◽

Superior Performance ◽

Control Group ◽

P Value ◽

Lasso Regression

Abstract Objectives To compare the performance of the PRECISE scoring system against several MRI-derived delta-radiomics models for predicting histopathological prostate cancer (PCa) progression in patients on active surveillance (AS). Methods The study included AS patients with biopsy-proven PCa with a minimum follow-up of 2 years and at least one repeat targeted biopsy. Histopathological progression was defined as grade group progression from diagnostic biopsy. The control group included patients with both radiologically and histopathologically stable disease. PRECISE scores were applied prospectively by four uro-radiologists with 5–16 years’ experience. T2WI- and ADC-derived delta-radiomics features were computed using baseline and latest available MRI scans, with the predictive modelling performed using the parenclitic networks (PN), least absolute shrinkage and selection operator (LASSO) logistic regression, and random forests (RF) algorithms. Standard measures of discrimination and areas under the ROC curve (AUCs) were calculated, with AUCs compared using DeLong’s test. Results The study included 64 patients (27 progressors and 37 non-progressors) with a median follow-up of 46 months. PRECISE scores had the highest specificity (94.7%) and positive predictive value (90.9%), whilst RF had the highest sensitivity (92.6%) and negative predictive value (92.6%) for predicting disease progression. The AUC for PRECISE (84.4%) was non-significantly higher than AUCs of 81.5%, 78.0%, and 80.9% for PN, LASSO regression, and RF, respectively (p = 0.64, 0.43, and 0.57, respectively). No significant differences were observed between AUCs of the three delta-radiomics models (p-value range 0.34–0.77). Conclusions PRECISE and delta-radiomics models achieved comparably good performance for predicting PCa progression in AS patients. Key Points • The observed high specificity and PPV of PRECISE are complemented by the high sensitivity and NPV of delta-radiomics, suggesting a possible synergy between the two image assessment approaches. • The comparable performance of delta-radiomics to PRECISE scores applied by expert readers highlights the prospective use of the former as an objective and standardisable quantitative tool for MRI-guided AS follow-up. • The marginally superior performance of parenclitic networks compared to conventional machine learning algorithms warrants its further use in radiomics research.

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Re: Long-Term Follow-up of a Large Active Surveillance Cohort of Patients with Prostate Cancer

The Journal of Urology ◽

10.1016/j.juro.2015.08.058 ◽

2015 ◽

Vol 194 (5) ◽

pp. 1286-1286

Author(s):

Samir S. Taneja

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Long Term Follow Up

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MP48-17 DO PROGRESSION RATES ON FOLLOW UP BIOPSY OVER TIME DIFFER BETWEEN MEN WITH VERY LOW RISK AND LOW RISK PROSTATE CANCER ON ACTIVE SURVEILLANCE?

The Journal of Urology ◽

10.1097/01.ju.0000556405.39904.0b ◽

2019 ◽

Vol 201 (Supplement 4) ◽

Author(s):

Srinath Kotamarti* ◽

Andrew Wood ◽

Alyssa Yee ◽

Daniel Rabinowitz ◽

Allison Marziliano ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Low Risk ◽

Risk Prostate Cancer ◽

Low Risk Prostate Cancer ◽

Over Time

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Nine-year Follow-up for a Study of Diffusion-weighted Magnetic Resonance Imaging in a Prospective Prostate Cancer Active Surveillance Cohort

European Urology ◽

10.1016/j.eururo.2015.10.010 ◽

2016 ◽

Vol 69 (6) ◽

pp. 1028-1033 ◽

Cited By ~ 42

Author(s):

Daniel R. Henderson ◽

Nandita M. de Souza ◽

Karen Thomas ◽

Sophie F. Riches ◽

Veronica A. Morgan ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Prostate Cancer ◽

Magnetic Resonance ◽

Active Surveillance ◽

Resonance Imaging ◽

Diffusion Weighted ◽

Weighted Magnetic Resonance Imaging

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Adverse pathology as a predictor of distant metastasis and prostate cancer mortality with 20-year follow up.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.219 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 219-219

Author(s):

Michael Austin Brooks ◽

Lewis Thomas ◽

Cristina Magi-Galluzi ◽

Jianbo Li ◽

Michael Crager ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Active Surveillance ◽

Distant Metastasis ◽

Cancer Mortality ◽

High Grade ◽

Intermediate Risk ◽

Sampling Weights ◽

Prostate Cancer Mortality

219 Background: Adverse pathology (AP) at radical prostatectomy (RP) is often used as a proxy for long-term prostate cancer outcomes. The goal of this study was to assess the association of AP at RP, defined as high-grade (> Grade Group 3) and/or non-organ confined disease (pT3), with distant metastasis and prostate cancer death. Methods: A stratified cohort sample of 428 patients was used to evaluate the association of adverse pathology with the risk of distant metastases and prostate cancer-specific mortality over 20 years after prostatectomy in 2641 patients treated between 1987-2004. Cox regression of cause-specific hazards was used to estimate the absolute risk of both endpoints, with death from other causes treated as a competing risk. Subgroup analysis in patients with low/intermediate risk disease potentially eligible for active surveillance was performed. Results: Among the 428 patients, 343 had AUA Low or Intermediate risk disease and 85 had High risk disease. Median follow-up time was 15.5 years (IQR 14.6–16.6 years). Using the cohort sampling weights for estimation, at RP 29.8% of patients had high-grade disease, 42.3 % had non-organ confined disease, 19.3% had both, and thus 52.8% had AP. Adverse pathology was highly associated with metastasis and prostate cancer mortality in the overall cohort (HR 12.30, 95% CI 5.30-28.55, and 10.03, 95% CI 3.42-29.47, respectively, both p<0.001), and in the low/intermediate risk subgroup potentially eligible for active surveillance (HR 10.48, 95% CI 4.18-26.28, and 8.60, 95% CI 2.40-30.84, respectively, both p≤0.001). Conclusions: Adverse pathology at radical prostatectomy is highly associated with future development of metastasis and prostate cancer mortality and may be used as a short-term predictor of outcomes. [Table: see text]

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Natural history of prostate cancer on active surveillance: stratification by MRI using the PRECISE recommendations in a UK cohort

European Radiology ◽

10.1007/s00330-020-07256-z ◽

2020 ◽

Cited By ~ 2

Author(s):

Francesco Giganti ◽

Armando Stabile ◽

Vasilis Stavrinides ◽

Elizabeth Osinibi ◽

Adam Retter ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Gleason Score ◽

Rank Test ◽

Gleason Grade ◽

Clinical Progression ◽

Radiological Progression ◽

Grade Group ◽

Psa Density

Abstract Objectives The PRECISE recommendations for magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer (PCa) include repeated measurement of each lesion, and attribution of a PRECISE radiological progression score for the likelihood of clinically significant change over time. We aimed to compare the PRECISE score with clinical progression in patients who are managed using an MRI-led AS protocol. Methods A total of 553 patients on AS for low- and intermediate-risk PCa (up to Gleason score 3 + 4) who had two or more MRI scans performed between December 2005 and January 2020 were included. Overall, 2161 scans were retrospectively re-reported by a dedicated radiologist to give a PI-RADS v2 score for each scan and assess the PRECISE score for each follow-up scan. Clinical progression was defined by histological progression to ≥ Gleason score 4 + 3 (Gleason Grade Group 3) and/or initiation of active treatment. Progression-free survival was assessed using Kaplan-Meier curves and log-rank test was used to assess differences between curves. Results Overall, 165/553 (30%) patients experienced the primary outcome of clinical progression (median follow-up, 74.5 months; interquartile ranges, 53–98). Of all patients, 313/553 (57%) did not show radiological progression on MRI (PRECISE 1–3), of which 296/313 (95%) had also no clinical progression. Of the remaining 240/553 patients (43%) with radiological progression on MRI (PRECISE 4–5), 146/240 (61%) experienced clinical progression (p < 0.0001). Patients with radiological progression on MRI (PRECISE 4-5) showed a trend to an increase in PSA density. Conclusions Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. Key Points • Patients without radiological progression on MRI (PRECISE 1–3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. • Clinical progression was almost always detectable in patients with radiological progression on MRI (PRECISE 4–5) during AS. • Patients with radiological progression on MRI (PRECISE 4–5) during AS showed a trend to an increase in PSA density.

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