Prostate Cancer Research International: Active Surveillance Research Articles

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong, China: what did we learn?

This study aimed to report the outcomes of active surveillance (AS) in the management of low-risk prostate cancer (PCa). It recruited 87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol with local adaptation at SH Ho Urology Centre, Prince of Wales Hospital, Hong Kong, China. We investigated the predictors of disease progression and found that baseline prostate-specific antigen density (PSAD) and the presence of the highest Prostate Imaging-Reporting and Data System (PI-RADS) score 5 lesion on magnetic resonance imaging (MRI) are significantly correlated with disease progression. Moreover, men with PSAD >0.2 ng ml-2 or PI-RADS 4 or 5 lesions had significantly worse upgrading-free survival compared to those with PSAD ≤0.2 ng ml-2 and PI-RADS 2 or 3 lesions. The study concludes that AS is a safe and effective management strategy for selected patients to defer radical treatment and that most disease progression can be detected after the first repeated biopsy. The combination of PSAD >0.2 ng ml-2 and PI-RADS 4 or 5 lesions may serve as a useful predictor of early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

Medium-term follow up of active surveillance for early prostate cancer at a non-academic institution.

To report oncological outcomes of active surveillance (AS) at a single non-academic institution adopting the standardised Prostate Cancer Research International Active Surveillance (PRIAS) protocol. Competing risk analyses estimated the incidence of overall mortality, metastases, conversion to treatment, and grade reclassification. The incidence of reclassification and adverse pathological findings at radical prostatectomy were compared between patients fulfilling all PRIAS inclusion criteria vs those not fulfilling at least one. We analysed 341 men with Grade Group 1 prostate cancer (PCa) followed on AS between 2010 and 2022. There were no PCa deaths, two patients developed distant metastases and were alive at the end of the study period. The 10-year cumulative incidence of metastases was 1.9% (95% confidence interval [CI] 0.33-6.4%). A total of 111 men were reclassified, and 127 underwent definitive treatment. Men not fulfilling at least one PRIAS inclusion criteria (n = 43) had a higher incidence of reclassification (subdistribution hazards ratio 1.73, 95% CI 1.07-2.81; P = 0.03), but similar rates of adverse pathological findings at radical prostatectomy. Metastases in men on AS at a non-academic institution are as rare as those reported in established international cohorts. Men followed without stringent inclusion criteria should be counselled about the higher incidence of reclassification and reassured they can expect rates of adverse pathological findings comparable to those fulfilling all criteria. Therefore, AS should be proposed to all men with low-grade PCa regardless of whether they are followed at academic institutions or smaller community hospitals.

MP43-08 ACTIVE SURVEILLANCE FOR PROSTATE CANCER: UPTAKE OVER TIME AND THE IMPACT OF AN ORGANIZED PROTOCOL

You have accessJournal of UrologyCME1 May 2022MP43-08 ACTIVE SURVEILLANCE FOR PROSTATE CANCER: UPTAKE OVER TIME AND THE IMPACT OF AN ORGANIZED PROTOCOL Sebastiaan Remmers, and Monique Roobol Sebastiaan RemmersSebastiaan Remmers More articles by this author , and Monique RoobolMonique Roobol More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002609.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The European Randomized Study of Screening for Prostate Cancer (ERSPC) showed that PSA-based screening coincides with overdiagnosis and overtreatment. Active Surveillance (AS) was initiated to reduce the harm of overtreatment. However, the rate of uptake of AS is highly heterogeneous around the world. Here, we look at the uptake of AS over time. Specifically, we assessed whether the initiation of an organized protocol increased the rate of men opting for AS and looked at differences between screening and clinical setting. METHODS: Data include diagnoses in the period 1993-2013 in men aged ≤70 yr diagnosed within ERSPC Rotterdam and eligible for AS according to the Prostate cancer Research International: Active Surveillance (PRIAS) pre-MRI criteria (Gleason 6, PSA <10 ng/ml, ≤cT2a). The number of PRIAS eligible men was compared against all men with low-risk disease in both arms of the trial and we assessed the choice of initial treatment for PRIAS eligible men before and after 2006 (the year PRIAS was initiated). RESULTS: In the study period, 962 men in the screening (S-) arm and 265 men in the control (C-) arm were diagnosed with cT1c/cT2a Gleason 6 disease (Tab/Fig). The percentage of PRIAS eligible men in this group is very different: 91% in the S-arm and 63% in the C-arm, reflecting lead time (lower PSA and tumor load). In the 90s and before PRIAS was initiated (i.e. <2006), 22% of all PRIAS eligible men in the S- arm opted for AS and 77% for radical prostatectomy (RP) / radiotherapy (RT); in the C- arm 27% opted for AS and 68% for RP/RT. From 2006 (initiation of PRIAS) till 2013 63% of the PRIAS eligible men in the S-arm opted for AS and 34% for RP/RT; in the C- arm 47% of the PRIAS eligible men opted for AS and 47% for RP/ RT. A difference most likely due to (although eligible for AS according to the PRIAS criteria) higher PSA values at diagnosis in the C- arm (median 6.2 ng/ml) than in the S-arm (median 3.9 ng/ml). CONCLUSIONS: In conclusion, PSA-based screen-detected low risk PCa is in general suitable for an AS approach. The initiation and awareness of an organized protocol for AS has increased the uptake in men diagnosed with low-risk PCa, but there is certainly still room for improvement. Since (opportunistic) early detection practices are ubiquitous, next to avoiding overdiagnosis, the use of AS in clinical practice should be strongly encouraged. Source of Funding: No © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e743 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sebastiaan Remmers More articles by this author Monique Roobol More articles by this author Expand All Advertisement PDF DownloadLoading ...

Impact of health-related quality of life on repeat protocol biopsy compliance on active surveillance for favorable prostate cancer: results from a prospective cohort in the PRIAS-JAPAN study.

This study aimed to evaluate how health-related quality of life (HRQOL) is related to repeat protocol biopsy compliance. We conducted a retrospective analysis using data from a prospective cohort in the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study between January 2010 and August 2019. We used the Short Form 8 Health Survey (SF-8), as patient-reported outcomes, to assess HRQOL at AS enrollment and the first year of the protocol. The physical component summary (PCS) and mental component summary (MCS) were calculated from SF-8 questionnaires. The primary outcome was the evaluation of the association of HRQOL at enrollment on the first repeat biopsy compliance. The secondary outcome was the comparison of SF-8 scores during AS, stratified by repeat protocol biopsy compliance. Of 805 patients who proceeded to the first year of the protocol, the non-compliance rate was 15% (121 patients). In the adjusted model, lower MCS at enrollment was significantly associated with the first repeat protocol biopsy non-compliance (odds ratio [OR], 2.134; 95% confidence interval [CI], 1.031-4.42; P = 0.041) but not in lower PCS (OR, 0.667; 95% CI, 0.294-1.514; P = 0.333). All subscales of SF-8 were lower in the non-compliance group than in the compliance group at any point. MCS in the non-compliance group improved over time from the time of AS enrollment (2.34 increased, P = 0.152). Our data suggest that lower MCS at AS enrollment using patient-reported outcomes was negatively associated with the first repeat protocol biopsy compliance. Our study may support the availability of a simple questionnaire to extract non-compliance.

Longitudinal evaluation of apparent diffusion coefficient values as a predictor of Prostate Cancer Research International Active Surveillance reclassification.

This study aimed to evaluate the effectiveness of apparent diffusion coefficient (ADC) parameters in distinguishing between Prostate Cancer Research International Active Surveillance (PRIAS) non-reclassification and reclassification groups during active surveillance (AS) of prostate cancer. We included 55 patients who fulfilled the PRIAS criteria and underwent ≥ 2 magnetic resonance imaging (MRI) including diffusion-weighted imaging with an interval of ≤ 3years between baseline and second MRI. A mono-exponential fitting model was used to automatically create ADC maps with minimum b-values of 0 and maximum of 2000s/mm2. For detectable lesions on ADC maps, the lesions were manually segmented on each slice of the ADC maps. For undetectable lesions, the corresponding normal-appearing zone of the lobe on each slice of ADC maps was segmented. The ADC data for each slice were summed to obtain the 25th, 50th, and 75th percentile ADC values of the histogram at baseline and second MRI. These ADC parameters at baseline and second MRI, and the changes of ADC parameters from baseline to second MRI were compared between PRIAS non-reclassification and reclassification groups. The PRIAS reclassification group had significantly lower 25th, 50th, and 75th percentile ADC values at second MRI compared to the non-reclassification group. The non-reclassification group had significantly lower changes in ADC values in these percentiles compared to the reclassification group. The ADC parameters at second MRI and the changes from baseline to second MRI may be effective distinguishing factors between PRIAS non-reclassification and reclassification groups.

Active surveillance for prostate cancer.

Many men diagnosed with localized prostate cancer can postpone definitive treatment without raising their risk of metastasis or death from disease. Active surveillance (AS) is a method of monitoring select men, with the option of switching to active treatment upon signs of progression, thereby avoiding the well-known side-effects of surgery and radiotherapy. This review analyzes the data from long-running AS cohorts to determine the safety and efficacy of AS. We conducted a narrative review of recently published data, including 14 articles from 13 AS cohorts. The cohorts used varying inclusion criteria, with reported differences in clinical T stage and Gleason Score (Grade Group), among other features. Some studies (n=5) limited their cohorts to low-risk patients, while others (n=8) also included intermediate-risk patients. The heterogeneity of the cohorts produced mixed results, with the risk of prostate cancer metastasis ranging from 0.1–1.0% at 10 years and the risk of prostate cancer mortality ranging from 0–1.9% at 10 years. However, the majority of studies reported risks of less than 0.5% at 10 years for both metastasis and death. For most cohorts, half of men remained untreated for 5–10 years, with estimates ranging from 37% receiving active treatment in the Toronto cohort to 73% in the Prostate Cancer Research International AS (PRIAS) study. Current data do not support the use of negative magnetic resonance imaging (MRI) to avoid scheduled biopsy. Taken together, the data collected from these AS cohorts suggests that AS is a safe approach for men with low-grade prostate cancer and some men with intermediate risk disease. AS should be more broadly implemented for eligible patients to avoid the decreases in quality of life from undergoing active treatment. Studies expanding the inclusion criteria and further defining a subset of men with favorable intermediate-risk prostate cancer who might safely benefit from AS are needed to assess the long-term outcomes of using AS in intermediate-risk groups.

P1037 - Impact of health-related quality of life on repeat protocol biopsy compliance on active surveillance for favorable prostate cancer: Results from a prospective cohort in the PRIAS-JAPAN study

Abstract Objectives This study aimed to evaluate how health-related quality of life (HRQOL) is related to repeat protocol biopsy compliance. Materials and methods We conducted a retrospective analysis using data from a prospective cohort in the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study between January 2010 and August 2019. We used the Short Form 8 Health Survey (SF-8), as patient-reported outcomes, to assess HRQOL at AS enrollment and the first year of the protocol. The physical component summary (PCS) and mental component summary (MCS) were calculated from SF-8 questionnaires. The primary outcome was the evaluation of the association of HRQOL at enrollment on the first repeat biopsy compliance. The secondary outcome was the comparison of SF-8 scores during AS, stratified by repeat protocol biopsy compliance. Results Of 805 patients who proceeded to the first year of the protocol, the non-compliance rate was 15% (121 patients). In the adjusted model, lower MCS at enrollment was significantly associated with the first repeat protocol biopsy non-compliance (odds ratio [OR], 2.134; 95% confidence interval [CI], 1.031-4.42; P = 0.041) but not in lower PCS (OR, 0.667; 95% CI, 0.294-1.514; P = 0.333). All subscales of SF-8 were lower in the non-compliance group than in the compliance group at any point. MCS in the non-compliance group improved over time from the time of AS enrollment (2.34 increased, P = 0.152). Conclusion Our data suggest that lower MCS at AS enrollment using patient-reported outcomes was negatively associated with the first repeat protocol biopsy compliance. Our study may support the availability of a simple questionnaire to extract non-compliance.

The impact of age on pathological insignificant prostate cancer rates in contemporary robot-assisted prostatectomy patients despite active surveillance eligibility.

The aim of this study was to assess insignificant prostate cancer (iPCa) rates after robot-assisted radical prostatectomy (RARP) in contemporary patients who were preoperatively eligible for active surveillance (AS). iPCa indicates no risk of PCa progression. We retrospectively analyzed 2837 RARP patients (2010-2019) who fulfilled at least one AS entry criteria set: Prostate Cancer Research International - Active Surveillance (PRIAS), University of California San Francisco (UCSF) (San Francisco, CA, USA), National Comprehensive Cancer Network (NCCN) or University of Toronto, ON, Canada. We utilized four different iPCa definitions: 1) based on pT2 and Gleason Score ≤6 and also cumulative tumor-volume; 2) ≤2.5mL; 3) ≤0.7mL; or 4) ≤0.5mL. For each AS set we tested the rates of iPCa and compared between age <70 vs. ≥70 years. This was complemented by multivariable logistic regression (LRM) predicting iPCa, adjusted for age and clinical AS variables. Finally, within the subgroup who had iPCa, we tested the rate of those who were deemed preoperatively AS ineligible. Between most (PRIAS) and least stringent (TORONTO) AS sets, iPCa was correctly predicted in 70-57%. Similarly, for iPCa definitions 2-4, rates were 59-42%, 34-19% and 27-14%. Senior patients harbored decreased proportions of iPCa. LRM confirmed that advanced age is associated with a lower chance of iPCa. More stringent AS sets lead to higher rates of AS ineligibility, e.g. 53% for PRIAS, despite iPCa. AS sets show limited accuracy for stricter iPCa definitions, which further declined with advanced age. Greater AS stringency resulted in more AS ineligible patients despite harboring iPCa. In consequence, patients are at risk for overtreatment. Clinicians must consider age and different AS sets that result in highly variable detection rates of iPCa.

P2PSA-associated parameters are significant predictors of reclassification of first-year protocol biopsy on active surveillance for early-stage prostate cancer patients: From the PRIAS-JAPAN study.

153 Background: 44 Japanese institutions have joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study as PRIAS-JAPAN. As an side study, PRIAS-JAPAN investigates the usefulness of [-2] proPSA (p2PSA), a precursor of PSA, as a predictive marker for the reclassification during active surveillance patients. In this study, we aimed to evaluate the usefulness of p2PSA related parameters to predict the reclassification of first year protocol biopsy (1yr PBx). Methods: 19 institutions participated in this side study which started in January 2013. All participants were eligible for PRAIS inclusion criteria. These patients were required to receive blood sampling on every visit and protocol biopsy after inclusion. PSA and PSA isoforms (free-PSA, p2PSA) were measured in serum samples and parameters (%free-PSA, %p2PSA, phi) were also calculated. Mann-Whitney U test was used to compare continuous variables between reclassification and non-reclassification groups. Fisher's exact test and Chi-squared test with yates' continuity correction were used for categorical variables. Multivariable logistic regression models were used to predict the risk of reclassification. To assess the predictive power for reclassification, we plotted ROC curves and calculated the AUC. Decision curve analysis (DCA) was used to evaluate whether adding variables to the baseline (age, PSA, prostate volume) model would yield net clinical benefit. Results: From January 2013 to July 2017, this study enrolled 237patients. 99 patients were excluded for the reason of discontinuation of AS, non-adherence of protocol blood sampling and rejection of biopsy. 138patients were able to analyzed PSA, PSA isoforms and its parameters at the time of inclusion and 1yr PBx. Patients who showed reclassification were significantly higher level of %p2PSA at inclusion and %p2PSA and phi just before 1yr PBx. Multivariate analyses showed %p2PSA at inclusion (p= 0.04), %p2PSA (p= 0.01) and Phi (p= 0.008) before 1yr PBx were statistically significant predictors of reclassification at 1yr PBx. ROC analysis revealed that %p2PSA before 1yr PBx (AUC 0.674) and phi before 1yr PBx (AUC 0.669) were a significant discriminant factor in predicting reclassification. DCA analysis showed that phi before 1yr PBx had a highest net benefit in the range of clinically plausible risk threshold (10–40%). Conclusions: %p2PSA and Phi before 1yr PBx have good prediction power and phi is a most useful indicator of clinical decision making about active surveillance. Clinical trial information: UMIN 000009876.

Supporting Patients With Untreated Prostate Cancer on Active Surveillance: What Causes an Increase in Anxiety During the First 10 Months?

BackgroundThe psychological burden possibly deriving from not immediately undergoing radical treatment for prostate cancer (PCa) could be a potential disadvantage of active surveillance (AS), especially in the eve of some relevant clinical exams [i.e., re-biopsy, prostate-specific antigen (PSA) test, and medical examination]. Even if it is known from the literature that the majority of PCa men in AS do not report heightened anxiety, there is a minority of patients who show clinically significant levels of anxiety after diagnosis. The present study aimed to investigate if demographic, clinical, and psychological variables at the entrance in AS (T0) were associated with the risk of developing clinically significant PCa-related anxiety 2 months before the first re-biopsy (T1) and to offer psychological support to improve quality of life (QoL).Materials and MethodsA total of 236 patients participated in the PCa Research International: AS (PRIAS) protocol and in PRIAS-QoL study. Demographic/clinical features, health-related QoL domains, coping with cancer, PCa-related anxiety [Memorial Anxiety Scale for PCa (MAX-PC)], personality traits, and decision-making-related factors were assessed at T0. MAX-PC was also administered at T1. PCa-related anxiety at T1 was considered to be of clinical significance if the MAX-PC score was ≥1.5. Multivariable logistic regression coupled to bootstrap was used to detect factors associated with high levels of anxiety.ResultsThe median age was 64.4 years. Fifty-six patients (24%) reported MAX-PC total score above the cutoff. Three factors were associated with a high level of PCa anxiety at T1: anxious preoccupation [odds ratio (OR) = 4.36], extraversion (OR = 1.9), and prostate-related symptoms (median OR = 0.46). Physical well-being was associated with a low PCa anxiety subscale (median OR = 0.15); neuroticism and functional well-being were associated with PSA anxiety (median OR = 7.05 and 0.73, respectively). Neuroticism and helplessness/hopelessness were associated with fear of progression (median OR = 18.1 and 5.8, respectively).ConclusionOnly a partial portion of the sample experienced significant levels of anxiety after 10 months. Psychological assessment should be routinely conducted to detect risk factors (i.e., anxious preoccupation, extraversion) for increased anxiety, offering tailored psychological interventions aimed at promoting interpersonal awareness and emotional well-being.

Clinical evaluation and disease management of PI-RADS 3 lesions. Analysis from a single tertiary high-volume center

Objective To evaluate the clinical and pathological implications of Prostate Cancer (PCa) patients with a Prostate Imaging - Reporting and Data System (PI-RADS) 3 lesion at multi parametric magnetic resonance imaging (mpMRI). Methods We included 356 patients with a PI-RADS score 3 lesion at mpMRI who underwent prostate biopsy for a suspect of PCa at a single tertiary high-volume centre between 2013 and 2016. We developed Uni- (UVA) and multi variable (MVA) logistic regression analyses assessing the predictors of three endpoints: 1) diagnosis of PCa, 2) active surveillance (AS) criteria and 3) clinically significant (CS) PCa at final pathology. Results PCa was diagnosed in 285 patients (80%), out of these 154 (56%) were eligible for AS according to Prostate Cancer Research International Active Surveillance (PRIAS) criteria. Over the 228 (64%) patients who underwent surgery, 93 (40.8%) had a CS disease at final pathology. Hundred and ninety-three (84.6%) had a pT2 disease and 35 (15.4%) had a pT3 disease. The size of the main lesion, age, PSA and prostate volume efficiently predicted PCa at MVA (all p < 0.05). None of our predictors were significantly associated with AS characteristics. Over those patients who underwent surgery, the biopsy Gleason Score (p = 0.007) efficiently predicted a CS PCa at final pathology. Conclusions mpMRI-detected PI-RADS 3 lesions should be sent to a prostate biopsy if other clinical parameters suggest the presence of a PCa. In case of diagnosis of a PCa, patients should undergo confirmatory biopsy before being included in AS protocols to avoid underestimation of a CS disease.

The impact of complications after initial prostate biopsy on repeat protocol biopsy acceptance rate. Results from the Prostate Cancer Research International: Active Surveillance JAPAN study.

Patients with favorable-risk prostate cancer on active surveillance (AS) are strictly followed for safer execution. Repeat protocol biopsy is essential for evaluating cancer aggressiveness. However, the acceptance rate of repeat biopsy is not high enough because of the burdens of biopsy. We assessed the impact of complications after the initial biopsy on repeat protocol biopsy at 1year using data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study. We performed a retrospective analysis using a prospective cohort in the PRIAS-JAPAN study. Patients with favorable-risk prostate cancer (n = 856) who consented to participate in the PRIAS-JAPAN study from 2010 to 2018 were enrolled. Follow-up evaluations included regular prostate-specific antigen, digital rectal examination and biopsy. Rates of complications after biopsies and repeat protocol biopsy non-acceptance rate at 1year were reported. Logistic regression analysis explored the association between the complications after the initial biopsy and repeat protocol biopsy non-acceptance. Altogether, 759 patients (88.7%) actually proceeded to protocol at 1year. Repeat protocol biopsy non-acceptance rate at 1year was 14.9%. Regarding complications after the initial biopsy, hematuria (p = 0.028) and pain (p < 0.001) rates were significantly higher in the repeat biopsy non-acceptance group, but infection (p = 0.056) and hematospermia (p = 0.337) rates were not different. On multivariate logistic regression analysis, pain was a significant predictor for repeat protocol biopsy non-acceptance (odds ratio 4.68, 95% confidence interval 1.864-11.75; p = 0.001). Pain at the initial biopsy negatively impacts patients' compliance with further protocol biopsies during AS.

Multiparametric magnetic resonance imaging and clinical variables: Which is the best combination to predict reclassification in active surveillance patients?

Introduction & objectivesWe tested the role of multiparametric magnetic resonance imaging (mpMRI) in disease reclassification and whether the combination of mpMRI and clinicopathological variables could represent the most accurate approach to predict the risk of reclassification during active surveillance.Materials & methodsThree-hundred eighty-nine patients (pts) underwent mpMRI and subsequent confirmatory or follow-up biopsy according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol. Pts with negative (−) mpMRI underwent systematic random biopsy. Pts with positive (+) mpMRI [Prostate Imaging Reporting and Data System, version 2 (PI-RADS-V2) score ≥3] underwent targeted + systematic random biopsies. Multivariate analyses were used to create three models predicting the probability of reclassification [International Society of Urological Pathology ≥ Grade Group 2 (GG2)]: a basic model including only clinical variables (age, prostate-specific antigen density, and number of positive cores at baseline), an Magnetic resonance imaging (MRI) model including only the PI-RADS score, and a full model including both the previous ones. The predictive accuracy (PA) of each model was quantified using the area under the curve.ResultsmpMRI negative (−) was recorded in 127 (32.6%) pts; mpMRI positive (+) was recorded in 262 pts: 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. At a median follow-up of 12 months, 125 pts (32%) were reclassified to GG2 prostate cancer. The rate of reclassification to GG2 prostate cancer was 17%, 35%, 38%, and 52% for mpMRI (−), PI-RADS 3, 4, and 5, respectively (P < 0.001). The PA was 69% and 64% in the basic and MRI models, respectively. The full model had the best PA of 74%: older age (P = 0.023; Odds ratio (OR) = 1.040), prostate-specific antigen density (P = 0.037; OR = 1.324), number of positive cores at baseline (P = 0.001; OR = 1.441), and PI-RADS 3, 4, and 5 (overall P = 0.001; OR = 2.458, 3.007, and 3.898, respectively) were independent predictors of reclassification.ConclusionsDisease reclassification increased according to the PI-RADS score increase, at confirmatory or follow-up biopsy. However, a no-negligible rate of reclassification was found also in cases of mpMRI (−). The combination of mpMRI and clinicopathological variables still represents the most accurate approach to pts on active surveillance.

The impact of complications after diagnostic biopsy on repeat biopsy in men: Results from the Prostate Cancer Research International: Active surveillance (PRIAS-JAPAN) study.

e17616 Background: Active surveillance(AS) is the strategy to avoid the overtreatment for favorable prostate cancer. For safer AS protocol execution, repeat protocol biopsy is essential in evaluating cancer aggressiveness accurately. However, some men on AS refuse repeat protocol biopsy because of burdens on biopsy. We aimed to assess the complications of prostate biopsy and the impact of complications after diagnostic biopsy on repeat protocol biopsy from the analysis Japanese cohort forming part of the Prostate cancer Research International: Active surveillance (PRIAS) study. Methods: PRIAS-JAPAN started in January 2010, 39 institutions are participating in this study. Men are prospectively followed and repeat protocol biopsy are planned at 1 year and 4 years thereafter, or if prostate specific antigen-doubling time is &lt; 10 years. Data was collected on the complications such as infection, hematuria, hematospermia, pain, and antibiotics, and approach of biopsy, retrospectively. We compared the complications in diagnostic biopsy between repeat biopsy acceptance group and repeat biopsy non-acceptance group at 1 year. Results: From 2010 to 2018, 862 men with low-risk prostate cancer were prospectively enrolled in PRIAS-JAPAN. 794 men (92%) actually proceeded to protocol at 1 year. Of the 794 men, repeat protocol biopsy non-acceptance rate at 1 year was 18.4%(146 men). According to differences in the complications of diagnostic biopsy, hematuria(p = 0.003) and pain(p &lt; 0.001) rate were significantly higher in repeat biopsy non-acceptance group, but infection(p = 0.105) and hematospermia(p = 0.224). Approach of biopsy(p = 0.651) was not different in two groups. Conclusions: Hematuria and pain in diagnostic biopsy were significantly more frequent in repeat biopsy non-acceptance group. Our study supports the importance of adequate explanation and management of the complications at biopsy to improve the rate of protocol biopsy acceptance. [Table: see text]

A novel nomogram to identify candidates for active surveillance amongst patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 or ISUP GG2 prostate cancer, according to multiparametric magnetic resonance imaging findings

ObjectivesTo develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low‐risk classification, and (iv) EAU low‐risk or low‐volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification.Patients and MethodsWe selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low‐risk, and EAU low‐risk or low‐volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate‐specific antigen density (PSA‐D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging‐Reporting and Data System (PI‐RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI‐RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used.ResultsOf the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low‐risk, EAU low‐risk or low‐volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low‐risk, EAU low‐risk or low‐volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA‐D, ISUP GG, PI‐RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P &lt; 0.001). The adoption of a 25% nomogram threshold increased the proportion of AS‐eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (Δ: −14.3%), JH (Δ: −5.9%), EAU low‐risk (Δ: −17.2%), and EAU low‐risk or low‐volume ISUP GG2 classifications (Δ: −18.0%).ConclusionThe novel nomogram combining clinical, biopsy and mpMRI findings was able to increase by ~25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, the PRIAS or JH criteria. Moreover, this nomogram significantly reduced the estimated frequency of csPCa that would be recommended for AS compared to, respectively, the PRIAS, JH, EAU low‐risk, and EAU low‐risk or low‐volume ISUP GG2 classifications.

Adherence to Active Surveillance Protocols for Low-risk Prostate Cancer: Results of the Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance Initiative

BackgroundActive surveillance (AS) enrolment criteria and follow-up schedules for low-risk prostate cancer vary between institutions. However, uncertainty remains about adherence to these protocols. ObjectiveTo determine adherence to institution-specific AS inclusion criteria and follow-up schedules within the Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative. Design, setting, and participantsWe retrospectively assessed the data of 15 101 patients from 25 established AS cohorts worldwide between 2014 and 2016. Outcome measurements and statistical analysisAdherence to individual AS inclusion criteria was rated on a five-point Likert scale ranging from poor to excellent. Nonadherence to follow-up schedules was defined as absence of repeat biopsy 1 yr after the scheduled date. Cohorts were pooled into annual and Prostate Cancer Research International: Active Surveillance (PRIAS)-based biopsy schedules, and a generalised linear mixed model was constructed to test for nonadherence. Results and limitationsSerum prostate-specific antigen (PSA) inclusion criteria were followed in 92%, Gleason score (GS) criteria were followed in 97%, and the number of positive biopsy cores was followed in 94% of men. Both age and tumour stage (T stage) criteria had 99% adherence overall. Pooled nonadherence rates increased over time—8%, 16%, and 34% for annual schedules and 11%, 30%, and 29% for PRIAS-based schedules at 1, 4, and 7 yr, respectively—and did not differ between biopsy schedules. A limitation is that our results do not consider the use of multiparametric magnetic resonance imaging. ConclusionsIn on-going development of evidence-based AS protocols, variable adherence to PSA and GS inclusion criteria should be considered. Repeat biopsy adherence reduces with increased duration of surveillance, independent of biopsy frequency. This emphasises the importance of risk stratification at the commencement of AS. Patient summaryWe studied adherence to active surveillance protocols for prostate cancer worldwide. We found that inclusion criteria were generally followed well, but adherence to repeat biopsy reduced with time. This should be considered when optimising future active surveillance protocols.

Outcomes of the patients with pT0 on first protocol biopsy during active surveillance for early prostate cancer: From the PRIAS-JAPAN study.

20 Background: We assessed the outcomes of the patients with pT0 on first protocol biopsy during active surveillance(AS) from the analysis Japanese cohort forming part of the Prostate Cancer Research International: Active Surveillance (PRIAS) study. Methods: PRIAS-JAPAN started in January 2010. 39 institutions are participating in this study. The inclusion criteria for the PRIAS study are as follows: clinical stage T1c/T2, PSA ≤ 10 ng/ml, PSA density (PSAD) &lt; 0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score (GS) ≤ 6 at initial diagnostic biopsy.In this analysis, we defined the patients presenting no reclassification with cancer after first protocol biopsy as NR-CA group and the patients presenting no reclassification showing pT0 as NR-noCA group. We compared AS remaining rate, pathological outcomes in extra biopsy and second protocol biopsy at 4 years between two groups. Results: First protocol biopsy was performed on 514 patients. 191 patients were in NR-noCA group and 199 patients were in NR-CA group. Patients background of NR-noCA group was as follows: Median age was 68, median PSA was 5.6ng/ml, and median prostate volume was 38.4cc. T1c were in 183 and T2a were in 8. At the time of first protocol biopsy, there was no significant differences about PSA parameters and pathological factors between NR-noCA group and NR-CA group. Also, extra biopsy performing rate (NR-noCA group vs NR-CA group; 5.75% vs 7.53%) and implementation rate of second protocol biopsy at 4 years (75.6% vs 63.6%) showed no significant differences. On second protocol biopsy, number of cancer positive cores were significantly smaller and rate of pT0 was higher in NR-noCA group. After five years, both group showed comparable AS remaining rate (76.9 vs 75.3%). Thirty eight patients of NR-noCA group selected definitive therapy and surgery was the most frequently chosen treatment option. Conclusions: Although rate of pT0 on second biopsy was higher in NR-noCA group, there was no significant difference between both groups in AS remaining rate. The patients in NR-noCA group tended to choose surgery as a definitive therapy. Clinical trial information: UMIN000002874.

Making Active Surveillance a path towards health promotion: A qualitative study on prostate cancer patients' perceptions of health promotion during Active Surveillance.

Health promotion is a key aspect for health outcomes of prostate cancer (PCa) patients. However, it has been poorly explored among patients following monitoring programmes, for example Active Surveillance (AS). This study aimed to explore PCa patients' perceptions of health promotion during AS. An explorative qualitative research design was adopted. Four focus groups were used to collected data from 24 men enrolled in the Prostate Cancer Research International: AS (PRIAS) protocol. A thematic analysis with an inductive approach was performed. Participants described promoting health during AS as challenged by mental, age-related, informational and organisational issues. It was reported as an effort to stay in the present with a positive outlook, despite the worries for the future ("the mental theme"). It was perceived as impacted by being older and having to manage physical and mental struggles related to age ("the life-course theme"). It depended, in their accounts, on obtaining reliable information and personalised education ("the educational theme"). Finally, it was related on taking responsibility on the care process ("the organisational theme"). This study suggested ways of promoting health during AS that can help healthcare professionals and organisations building a "health-promoting AS," able to improve overall health outcomes.

Follow-up in Active Surveillance for Prostate Cancer: Strict Protocol Adherence Remains Important for PRIAS-ineligible Patients

BackgroundActive surveillance (AS) is a safe treatment strategy for men with low-risk prostate cancer (PC) when performed in a research setting using strict follow-up. However, less is known about the protocol adherence and outcomes for AS in real-world practice. ObjectiveTo evaluate Prostate Cancer Research International Active Surveillance (PRIAS) protocol adherence in a real-world cohort and to relate follow-up intensity to oncological safety. Design, setting, and participantsPatients with biopsy-detected PC diagnosed from 2008 to 2014 treated with AS at six teaching hospitals in The Netherlands. InterventionAS included regular prostate-specific antigen (PSA) testing (every 3–6mo) combined with a confirmatory biopsy 1yr after diagnosis and every 3yr thereafter. Outcome measurements and statistical analysisThe proportions of patients complying with the PRIAS biopsy and PSA monitoring protocol were determined. We assessed if PRIAS-discordant follow-up was associated with a higher risk of metastasis compared with PRIAS-concordant follow-up using Cox regression analysis. Analysis was performed for separate risk groups (PRIAS-eligible and PRIAS-ineligible) on the basis of the PRIAS inclusion criteria. Results and limitationsOf all patients on AS for >6mo, 706/958 (74%) had PRIAS-concordant PSA monitoring. Overall concordant follow-up (PSA and repeat biopsy) was observed in 415/958 patients (43%). The percentage of patients with overall concordant follow-up varied between hospitals (range 34–60%; p<0.001). Among PRIAS-ineligible patients, PRIAS-discordant PSA monitoring was associated with a higher risk of developing PC metastases during AS compared with patients with concordant follow-up (hazard ratio 5.25, 95% confidence interval 1.02–27.1). In the PRIAS-eligible population, we found no significant differences regarding rates of metastases between patients with discordant and concordant follow-up. ConclusionsWe observed substantial variation in AS follow-up intensity between large urological practices in the Netherlands. Overall, 43% of patients on AS in daily clinical practice receive PRIAS-concordant follow-up. Noncompliance with the PRIAS follow-up protocol was associated with a higher rate of metastasis among PRIAS-ineligible patients, indicating that strict protocol adherence is important when these patients opt for AS. Patient summaryFewer than half of patients with prostate cancer on active surveillance are monitored according to the follow-up protocol of the largest ongoing active surveillance study. Lower-intensity monitoring may be less safe for patients who are not in the lowest risk group.

The role of Prostate Imaging Reporting and Data System score in Gleason 3 + 3 active surveillance candidates enrollment: a diagnostic meta-analysis

The contemporary active surveillance (AS) criteria may result in an unsatisfactory misclassification rate, which may delay curative treatment for prostate cancer patients. The magnetic resonance imaging (MRI), not included in any AS criteria, provides useful information for prostate cancer diagnosis. Our goal is to evaluate the diagnostic performance of Prostate Imaging Reporting and Data Systems (PI-RADS) score, a standardized MRI reporting system, in AS candidates enrollment. We searched Cochrane CENTRAL, PubMed, and Embase for pertinent studies through June 2018. The standard methods recommended for meta-analyses of diagnostic evaluation were employed. We draw the summary receiver operating characteristic (SROC) curve. Meta-regression analysis was performed to evaluate the effects of confounding factors. From the resulting 168 studies, 5 provided the diagnostic data on PI-RADS score and pathological results; 834 patients were included. All AS candidates in these studies were defined by Prostate Cancer Research International: Active Surveillance (PRIAS) criterion. The pooled estimates of PI-RADS 4 or 5 on adverse pathological features at radical prostatectomy (RP) among AS candidates were: sensitivity, 0.77 (95% confidence interval (CI), 0.71-0.82); specificity, 0.63 (95% CI, 0.55-0.71); positive predictive value, 0.72 (95% CI, 0.64-0.79); negative predictive value, 0.68 (95% CI, 0.63-0.73); and diagnostic odds ratio, 6 (95% CI, 4-8). The SROC curve was positioned toward the desired upper left corner of the curve, the area under the curve was 0.77 (95% CI, 0.73-0.80). The P-value for heterogeneity was <0.01. The pathological outcomes and endorectal coils contributed to the heterogeneity of sensitivity. The evidences supporting the advantage of PI-RADS v2 over v1 were not sufficient yet. AS candidates with PI-RADS 4 or 5 may be unsuitable for AS even though they fulfill current AS criteria. Those with PI-RADS 3 or less indicated relative safety for AS enrollment.