Study Type – Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Active surveillance aims to reduce overtreatment by selecting patients with low risk prostate cancer (PCa) based on favourable disease characteristics. However, most studies on active surveillance do not have long‐term results available; in particular, data on patients with intermediate risk disease are lacking. Our findings demonstrate that withholding radical treatment in men with low or intermediate risk screen‐detected localized PCa leads to a substantial delay or even avoidance of radical treatment in a majority of men. Favourable disease‐specific outcomes confirm the feasibility of active surveillance for low risk PCa and also support a role for active surveillance in selected patients with intermediate risk PCa. OBJECTIVE To assess the longer‐term feasibility of active surveillance, we aimed to evaluate outcomes of patients with screen‐detected localized prostate cancer (PCa) who initially elected to withhold radical treatment for either low or intermediate risk disease. PATIENTS AND METHODS All men underwent screening for PCa in the Rotterdam and Helsinki arms of the European Randomized Study of Screening for Prostate Cancer (ERSPC); eligible men were diagnosed with PCa prior to the establishment of the ERSPC‐affiliated Prostate Cancer Research International: Active Surveillance (PRIAS) study (1994–2007) and were initially expectantly managed in the absence of a fixed follow‐up protocol. Low risk PCa was defined as clinical stage T1/T2, PSA ≤ 10 ng/mL, PSA density < 0.2 ng/mL/mL, Gleason ≤ 6 and maximum two positive biopsy cores, whereas PSA 10–20 ng/mL, Gleason score 7 and three positive biopsy cores were considered intermediate risk features. Disease‐specific, overall and treatment‐free survival were analysed using the Kaplan–Meier and competing risks methods. RESULTS In all, 509 patients with PCa were eligible, of whom 381 were considered low risk and 128 intermediate risk. During a median follow‐up of 7.4 years, a total of 221 patients (43.4%) switched to deferred treatment after a median of 2.6 years. The calculated 10‐year disease‐specific survival rates were 99.1% and 96.1% for low and intermediate risk patients, respectively (P= 0.44), and for overall survival 79.0% and 64.5%, respectively (P= 0.003). Competing risks analysis showed similar results. CONCLUSIONS Withholding radical treatment in men with low to intermediate risk screen‐detected PCa leads to a substantial delay or even avoidance of radical treatment and its potential side‐effects in a majority of patients. Disease‐specific outcomes at 7.4 years of follow‐up are favourable in low as well as intermediate risk patients. This confirms the feasibility of active surveillance according to contemporary criteria, and also suggests a potential role for active surveillance in selected men with intermediate risk features.
a Gleason score of ≤ 3 + 3 = 6, and one or two positive biopsy cores, were analysed. The follow-up protocol consisted of frequent PSA measurements, digital rectal examinations, and standard repeat biopsies (the first after 1 year). The primary outcome is survival free of active therapy; the secondary endpoints are reasons for stopping AS, findings in 1-year repeat biopsies, and outcomes after radical prostatectomy (RP). RESULTSPatients were included between December 2006 and July 2008. The median (25-75th percentile) follow-up after diagnosis was 1.02 (0.6-1.5) years. The 2-year survival rate free from active therapy was 73%. Of the 82 men who changed to active therapy during the follow-up, 68 (83%) did so based on the protocol. Of the 261 repeat biopsies available for analysis, 90 (34%) showed no cancer, while 57 (22%) showed a Gleason score of > 6 or more than two positive biopsy cores. There was a relatively unfavourable PSA doubling time of 0-10 years in 53% (102/194) and 62% (33/53) of men with favourable and unfavourable re-biopsy results, respectively. After RP, four of 24 (17%) men had T3 disease and 12 (50%) had a Gleason score of > 6. CONCLUSIONAS seems feasible, but mortality outcomes are unknown. A strict follow-up protocol including standard 1-year repeat biopsies resulted in a quarter of men stopping AS after 2 years.
The clinical course of prostate cancer is highly variable. Current prognostic variables, stage, and Gleason score have limitations in assessing treatment regimens for individual patients, especially in the intermediate-risk group of Gleason score 7. ERG:TMPRSS2 fusion and loss of PTEN are some of the most common genetic alterations in prostate cancer. Immunohistochemistry of PTEN and ERG has generated interest as a promising method for more precise outcome prediction but requires further validation in population-based cohorts. We studied the predictive value of ERG and PTEN expression by immunohistochemistry in two large radical prostatectomy cohorts comprising 815 patients with extensive follow-up information. Clinical end points were initiation of secondary therapy, overall survival, and disease-specific survival. Predictions of clinical outcomes were also assessed according to androgen receptor (AR) activity. PTEN loss, especially in ERG-negative cancers, predicted initiation of secondary treatments and shortened disease-specific survival time, as well as stratifying Gleason score 7 patients into different prognostic groups with regard to secondary treatments and disease-specific survival. High AR immunoreactivity in ERG-negative cancers with PTEN loss predicted worse disease-specific survival. We also observed that in Gleason score 7 ERG-negative cases with PTEN loss and high AR expression have significantly shorter disease-specific survival time compared with ERG-positive cases. Our conclusion is that loss of PTEN is a strong determining factor for shorter disease-specific survival time and initiation of secondary therapies after radical prostatectomy. The predictive value of PTEN immunoreactivity is further accentuated in ERG-negative cancers with high AR expression. Negative PTEN expression, accompanied by ERG status, can be used to stratify patients with Gleason score 7 into different survival groups. Assessment of PTEN and ERG status could provide an additional tool for initial diagnostics when determining the prognosis and subsequent follow-up regimen for patients treated by radical prostatectomy.
Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance is a management option in patients with localized prostate cancer. One concern is the possible psychological burden and quality‐of‐life effects caused by consciousness of living with untreated cancer. Previous studies have reported controversial results about the impact of active surveillance on patient's health‐related quality of life. The data of the present study support the idea that patients with low‐risk prostate cancer manage well on active surveillance and do not develop short‐term mental or physical quality‐of‐life sequelae. OBJECTIVE To analyse longitudinal changes in general, mental and physical health‐related quality of life (HRQL) and urinary and erectile function in patients with low‐risk prostate cancer (PC) on active surveillance (AS). PATIENTS AND METHODS Patients comprised those (n= 124) enrolled in the Finnish arm of the Prostate Cancer Research International: Active Surveillance (PRIAS) study who were followed for at least 1 year (n= 80). All patients with PC received validated questionnaires at the start of surveillance and after 1 year of follow‐up. General HRQL was assessed with the RAND 36‐Item Health Survey (RAND‐36), erectile function with the International Index of Erectile Function‐5 (IIEF‐5), and urinary symptoms with the International Prostate Symptom Score (IPSS) questionnaires. Results were also compared with an age‐stratified general Finnish male population. A paired t‐test served to compare results over time and a non‐paired t‐test or a corresponding non‐parametric test, when applicable, served to compare the study group with the general population. Pearson and Spearman correlations were analysed between possible HRQL‐affecting factors (demographic and clinical data) and HRQL data, followed by linear regression analysis to further evaluate any possible associations. RESULTS Of the 124 patients, 105 (85%) returned the baseline RAND‐36 questionnaire, and 75 (94%) of the 80 patients answered both the baseline and follow‐up questionnaires; 15 patients (12%) had discontinued AS, all for protocol‐based reasons, none due to anxiety or distress. No differences existed in the HRQL main categories at the 1‐year follow‐up (mental and physical: P= 0.142 and P= 0.154, respectively). When all the eight dimensions were analysed separately, the physical role showed statistically significant improvement from a mean of 81 to a mean of 89 (P= 0.010). No clinically significant correlations appeared between HRQL and age, diagnostic prostate‐specific antigen (PSA), free PSA or PSA change during follow‐up at any of the time points; in regression analysis, HRQL was not predictable by any of the variables available at diagnosis or during follow‐up. No statistically significant changes occurred in urinary function as analysed by the IPSS (P= 0.121) or in erectile function by the IIEF‐5 questionnaire (P= 0.583). Compared with an age‐stratified Finnish general male popula...
A simple diagnostic biopsy-based analysis of PTEN status may help identify patients with high risk for prostate cancer progression.
Localized low-grade prostate cancer is challenging to visualize in DW-MRI, and this imaging technique provides no additional prognostic benefit compared to PSA and repeat biopsies.
IntroductionThis study was conducted to describe the changes in repeat multiparametric MRI (mpMRI) occurring in prostate cancer (PCa) patients during active surveillance (AS), and to study possible associations between mpMRI-related parameters in predicting prostate biopsy (Bx) Gleason score (GS) upgrading >3+3 and protocol-based treatment change (TC).Materials and methodsThe study cohort consisted of 76 AS patients with GS 3+3 PCa and at least two consecutive mpMRIs of the prostate performed between 2006–2015. Patients were followed according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol and an additional mpMRI. The primary end points were GS upgrading (GU) (>3+3) in protocol-based Bxs and protocol-based TC.ResultsOut of 76 patients, 53 (69%) had progression (PIRADS upgrade, size increase or new lesion[s]), while 18 (24%) had radiologically stable disease, and 5 (7%) had regression (PIRADS or size decrease, disappearance of lesion[s]) in repeat mpMRIs during AS. PIRADS scores of 4–5 in the initial mpMRI were associated with GU (p = 0.008) and protocol-based TC (p = 0.009). Tumour progression on repeat mpMRIs was associated with TC (p = 0.045) but not with GU (p = 1.00). PIRADS scores of 4–5 predict GU (sensitivity 0.80 [95% confidence interval (CI); 0.51–0.95, specificity 0.62 [95% CI; 0.52–0.77]) with PPV and NPV values of 0.34 (95% CI; 0.21–0.55) and 0.93 (95% CI; 0.80–0.98), respectively.ConclusionmpMRI is a useful tool not only to select but also to monitor PCa patients on AS.
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