Infectious complications after transrectal MRI-targeted and systematic prostate biopsy.

PURPOSE: To compare infectious complications after transrectal systematic prostate biopsy (SB) and magnetic resonance imaging (MRI)-targeted biopsy (TB) in a large retrospective cohort to assess whether one technique is superior to the other regarding infectious complications. METHODS: A total of 4497 patients underwent 5288 biopsies, 2875 (54%) SB and 2413 (46%) MRI-TB only. On average, 12 SB cores and 3.7 MRI-TB cores were taken per biopsy session during the study period. Infection-related complications within 30 days were compared. The primary endpoint was a positive urine culture. Secondary endpoints were positive blood cultures, urine tests with elevated leukocytes ≥ 100 E6/L and elevated C-reactive protein (CRP) ≥ 100 mg/L. Chi-square test was used to compare the cohorts. RESULTS: Positive urine cultures were found in 77 (2.7%) after SB and in 42 (1.7%) after MRI-TB (p = 0.022). In total, 46 (0.9%) blood culture positive infections were found, 23 (0.9%) occurred after SB and 23 (1.0%) after MRI-TB, (p = 0.848). Urine tests with elevated leukocytes ≥ 100 E6/L were found in 111 (3.9%) after SB and in 61 (2.5%) after MRI-TB (p = 0.006). Elevated CRP ≥ 100 mg/L was found in 122 (4.2%) after SB and in 72 (3.0%) after MRI-TB (p = 0.015). Blood cultures were drawn more often after SB than after MRI-TB, but the difference was not statistically significant. However, urine cultures and CRP were taken more often after SB than MRI-TB. CONCLUSION: Blood culture positive infections were equally rare after SB and MRI-TB. However, all other infectious complications were more common after SB than MRI-TB.

Men's experiences of the impact of penile cancer surgery on their lives: A qualitative study.

OBJECTIVE: Surgery is the primary treatment for invasive penile cancer (PC). Postoperative changes in genital anatomy and function may lead to altered body and self-image, compromised sexual function and subsequent psychological problems. The aim of this study is to describe men's experiences of the impact of PC surgical treatment on their lives. METHODS: The institutional databases of two Finnish university hospitals were searched for patients who underwent surgery for invasive PC between 2009 and 2019. Of 107 men, 29 agreed to an interview or a response letter. The data were analysed by thematic analysis. RESULTS: The men experienced that their self-image had changed after PC diagnosis and treatment to a 'cancer-modified me'. They also experienced that physical symptoms after surgery defined their everyday, as well as sexual, lives and that the whole content of life changed. CONCLUSION: Support and counselling for physical, mental, sexual and social factors should be part of the treatment of men with PC.

Health-Related Quality of Life, Self-esteem and Sexual Functioning Among Patients Operated for Penile Cancer - A Cross-sectional Study.

BACKGROUND: Penile cancer surgery affects physical, psychological, and sexual well-being, but the patient- and treatment-related factors predisposing to worse health-related quality of life (HRQoL) have not been well characterized. AIM: We report treatment-related HRQoL changes among penile cancer survivors compared to the general population and the specific deficits that have the most profound effect, and we identify patient-related factors that predispose to a worse perceived HRQoL. METHODS: Patients (n = 107) who underwent operations for invasive penile cancer in two Finnish university hospitals from 2009 to 2019 were sent the Patient Reported Outcomes (PROs) questionnaire designed to measure HRQoL, self-esteem, overall sexual functioning, erections, and change in sexual function. We collected clinical information and socio-demographic characteristics, including age, partner status, children, vocational education, and employment status. Associations between patient- and treatment-related factors and HRQoL were analyzed using descriptive statistics and non-parametric tests. Linear regression models were used to compare the HRQoL differences between patients with penile cancer and the age-standardized average for the Finnish population. OUTCOMES: A generic measure of HRQoL (15D), the Rosenberg Self-Esteem Scale, Overall Sexual Functioning Questionnaire, the Erection Hardness Score, and self-reported change in sexual functioning. RESULTS: Low scores in overall sexual functioning, erectile function, and changes in sexual functioning were associated with a lower HRQoL. An association was found between HRQoL and age, educational level, employment status, and place of residence. The HRQoL had a negative correlation with age. Patients with a high educational level, who were employed, or who lived in urban areas reported higher HRQoL. The mean HRQoL of penile cancer survivors was significantly lower than the age-standardized average HRQoL of the Finnish population. CLINICAL IMPLICATIONS: Enhanced support and counseling is needed among penile cancer patients to improve the HRQoL during survivorship. STRENGTHS & LIMITATIONS: A nationwide sample with detailed information allowed comparisons of HRQoL between penile cancer patients and the general population. Due to cross-sectional nature of the study, the time between the surgery and the study intervention was heterogeneous, and this may have affected the results. CONCLUSION: Penile cancer patients exhibit significant physical and psychological dysfunction, and the lack of sexual activity in general is what most compromises the QoL of penile cancer survivors. Harju E, Pakarainen T, Vasarainen H, et al. Health-Related Quality of Life, Self-esteem and Sexual Functioning Among Patients Operated for Penile Cancer - A Cross-sectional Study. J Sex Med 2021;18:1524-1531.

Loss of PTEN expression in ERG-negative prostate cancer predicts secondary therapies and leads to shorter disease-specific survival time after radical prostatectomy.

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.

Predictive role of free prostate-specific antigen in a prospective active surveillance program (PRIAS).

PURPOSE: To evaluate the utility of percentage of free serum PSA (%fPSA) as a predictor of adverse rebiopsy findings, treatment change and radical prostatectomy (RP) findings in a prospective active surveillance (AS) trial. METHODS: Patients enrolled in the global PRIAS study with baseline %fPSA available were included. Putative baseline predictors (e.g. PSA, %fPSA) of adverse rebiopsy findings were explored using logistic regression analysis. Association of variables with treatment change and RP findings over time were evaluated with Cox regression analysis. Active treatment-free survival was assessed with a Kaplan-Meier method. RESULTS: Of 3701 patients recruited to PRIAS, 939 had %fPSA measured at study entry. Four hundred and thirty-eight of them had %fPSA available after 1 year. Median follow-up was 17.2 months. First rebiopsy results were available for 595 patients and of those, 144 (24.2 %) had adverse findings. A total of 283 (30.1 %) patients discontinued surveillance, of those 181 (64.0 %) due to protocol-based reasons. Although median %fPSA values were significantly lower in patients who changed treatment, according to the multivariate regression analysis, initial %fPSA value was not predictive for treatment change or adverse rebiopsy findings. However, the probability of discontinuing AS was significantly lower in patients with "favourable" initial %fPSA characteristics and %fPSA during follow-up (initial %fPSA ≥15 and positive %fPSA velocity) compared to those with "adverse" %fPSA characteristics (initial %fPSA <15 and negative %fPSA velocity). CONCLUSIONS: Diagnostic %fPSA provides no additional prognostic value when compared to other predictors already in use in AS protocols. However, %fPSA velocity during surveillance may aid in predicting the probability for future treatment change.

Effects of prostate cancer screening on health-related quality of life: results of the Finnish arm of the European randomized screening trial (ERSPC).

BACKGROUND: As prostate cancer (PC) mortality reduction results are not unequivocal, a special emphasis has to be put on other aspects of the prostate-specific antigen (PSA) screening, including effects on quality of life. In the present study we describe the short-term effects of various phases of PC screening on health-related quality of life (HRQL). MATERIAL AND METHODS: The study participants were randomized into the screening arm within the Finnish component of the European Randomized Study on Screening for Prostate Cancer (ERSPC). The RAND 36-Item Health Survey on HRQL and questionnaires on sociodemographic and behavioral factors were delivered to participants at various phases of the first screening round: 1) 500 participants at invitation; 2) 500 after screening; 3) 500 after obtaining the PSA result; 4) to 300 participants after undergoing digital rectal examination (DRE) (but prior to being informed of its result); and 5) approximately 300 after prostate biopsy. At each stage, a new sample of participants was recruited. RESULTS: Response rates were 59% at invitation, 77% after PSA blood test, 54% after PSA result and 69% after DRE. The men recruited at each stage were comparable in respect to socioeconomic variables. The HRQL scores in RAND-36 subscales showed little variation in the different phases of the screening process. Compared with the previous phase, the social function score was slightly lower after obtaining the PSA result than after blood test, the emotional role score lower after DRE than after PSA result and the pain-related score lower after DRE than after TRUS and biopsy. The screening participants were comparable to the general population as their HRQL scores were similar to an age-stratified general Finnish male population. CONCLUSION: Short-term HRQL effects of prostate cancer screening appear minor and transient.

Prostate cancer active surveillance and health-related quality of life: results of the Finnish arm of the prospective trial.

UNLABELLED: 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 population, patients with PC on AS had a significantly better general mental and physical HRQL at diagnosis and after 1 year of follow-up (P < 0.05). CONCLUSIONS: Active surveillance does not provoke short-term quality-of-life disturbances as assessed by standardized RAND-36, IIEF-5 and IPSS questionnaires. None of the patients changed treatment due to anxiety. Unexpectedly, PC patients on AS had significantly better general mental and physical HRQL than did a general age-stratified Finnish male population.

Outcomes of initially expectantly managed patients with low or intermediate risk screen-detected localized prostate cancer.

UNLABELLED: 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.

[Urinary retention in women]. / Naisen virtsaumpi.

Urinary retention can be either acute or chronic. Its causes can be divided into obstructive, neurologic and other causes. A woman's urinary retention is most commonly due to weakened power of the detrusor muscle. Treatment of urinary retention is determined on an etiological basis. Basic treatment of acute urinary retention is catheterization. In chronic retention, intermittent catheterization is often the most effective option. Neuromodulation may result in prolonged relief for carefully chosen patients. Few patients benefit from pharmacological treatments or surgery.

Prospective Longitudinal Health-related Quality of Life Analysis of the Finnish Arm of the PRIAS Active Surveillance Cohort: 11 Years of Follow-up.

BACKGROUND: Living with an untreated cancer may alter quality of life (QoL) in the long term. OBJECTIVE: To prospectively study long-term changes in general, mental, and physical QoL in a contemporary active surveillance (AS) patient cohort with low-risk prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: The study population consisted of patients enrolled in the PRIAS trial in Helsinki University Hospital (n = 348). The RAND-36 questionnaire was used to assess general QoL at the start of AS and at 1, 3, 5, 7, 9, and 11 years during follow-up. Patients who had undergone robot-assisted laparoscopic prostatectomy (RALP; n = 88) also received the questionnaire after treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Changes over time were analysed using multilevel mixed-effects regression models, and reported as the mean and95% confidence interval. A rule of 0.5 × standard deviation was used to estimate changes of clinical importance. RESULTS AND LIMITATIONS: Median follow-up until the end of AS or last follow-up was 7.2 (range 0.3-12.7) yr. A decrease was observed in six of eight QoL subdomains at 7 yr. However, all scores were above age-stratified reference values. There was no difference between the group who continued AS throughout the study period and the group who discontinued AS and underwent RALP. More than half of the study cohort discontinued AS (n = 198; 57%), 135 men (68%) because of events specified in the protocol and only seven (3.5%) because of anxiety. Metastatic disease developed in six patients (1.7%), and two cases (0.6%) of PCa-related death were recorded among 348 patients in more than 12 yr of overall follow-up. The lack of a randomised control population is a limitation of the study. CONCLUSIONS: Contemporary protocolised AS does not impair general QoL. Men undergoing a treatment change (RALP) did not experience a decrease in QoL before or after their treatment change. PATIENT SUMMARY: Active surveillance is a safe treatment option for men with low-risk prostate cancer. We show that this follow-up strategy does not cause a decline in patients' general quality of life.

[Active surveillance of prostatic cancer]. / Eturauhassyövän aktiiviseuranta.

Overdiagnosis of prostatic cancer easily leads to overtreatment, whereby the patients are also exposed to the adverse effects of the treatments. Active surveillance has been raised as an alternative to the treatments of prostatic cancer with a good prognosis. Active surveillance means that instead of immediate curative treatment, a patient suited for radical treatments by his age and condition is under careful monitoring. Active surveillance aims to pick out from the wide group of prostatic cancer patients those, who present sings of progressive disease, and to provide the curative treatment later, whereby harm-free lifetime will be extended.

Does Protocol Make a Difference? Comparison of Two Prostate Cancer Active Surveillance Cohorts: A Non-protocol-based Follow-up and a Protocol-based Contemporary Follow-up.

BACKGROUND: 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. OBJECTIVE: 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. DESIGN SETTING AND PARTICIPANTS: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS, CSS, MFS, and TFS were compared by the Kaplan-Meier method, competing risk analysis, and Cox proportional hazard regression. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.

Short-term outcomes of the prospective multicentre 'Prostate Cancer Research International: Active Surveillance' study.

OBJECTIVE: To evaluate the short-term outcomes of the prospective international Prostate Cancer Research International: Active Surveillance ('PRIAS') study (Dutch Trial Register NTR1718), as active surveillance (AS) for early prostate cancer might provide a partial solution to the current overtreatment dilemma in this disease. PATIENTS AND METHODS: The first 500 (of >950) participants with asymptomatic T1c/T2 prostate cancer, with a prostate-specific antigen (PSA) level of < or =10.0 ng/mL, a PSA density of <0.2 ng/mL/mL, a Gleason score of < or =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). RESULTS: Patients 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. CONCLUSION: AS 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.

[Treatment of localized prostate cancer having a good prognosis may cause more harm than benefit]. / Hyväennusteisen paikallisen eturauhassyövän hoidosta voi olla enemmän haittaa kuin hyötyä.

The extensive use of prostate-specific antigen determination has considerably increased the incidence of prostate cancer. Due to earlier diagnosis, localized small cancers are found that in all probability are clinically insignificant. Overdiagnosis leads to overtreatment and to significant adverse effects. Localized prostate cancers of elderly patients having multiple diseases have often merely been monitored without therapy. Active monitoring should now be adventured also for younger men, whose tumor fulfils the criteria of minimal cancer.

PTEN Loss but Not ERG Expression in Diagnostic Biopsies Is Associated with Increased Risk of Progression and Adverse Surgical Findings in Men with Prostate Cancer on Active Surveillance.

BACKGROUND: Active surveillance (AS) is an option for men with low-risk prostate cancer (PCa). PTEN and ERG have been considered as potential biomarkers of PCa progression and survival. OBJECTIVE: To study the role of ERG and PTEN status in the Prostate Cancer Research International: Active Surveillance (PRIAS) trial diagnostic biopsies (DBxs) in predicting surveillance discontinuation and adverse surgical findings in subsequent radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: A total of 231 patients were recruited to the PRIAS between 2007 and 2013 in Helsinki. DBx tissue for immunohistochemistry (IHC) was available from 190 patients. Tissue microarrays (TMAs) were constructed from 57 specimens of subsequent RPs. DBxs containing grade group (GG) 1 PCa and RP TMA sections were stained with ERG and PTEN antibodies, and scored as either negative or positive. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Outcomes were followed up by biopsy GG upgrade (GG ≥ 2) and protocol-based treatment change, as well as adverse findings in RP (GG ≥ 3 or pathological stage≥3). Clinical variables and biomarker status in DBx were correlated in Cox regression analysis and cumulative survival in Kaplan-Meier analysis, and finally, Gray's competing risk analysis was performed and nonprotocol-based discontinuation was considered as a competing event. RESULTS AND LIMITATIONS: In both uni- and multivariate Cox regression analyses, only the number of positive cores in the DBx, the number of rebiopsy sessions, and PTEN status at diagnosis were significantly associated with rebiopsy GG upgrade, treatment change, and adverse histopathology in RP. In Kaplan-Meier analysis, PTEN loss was associated with a shorter time to GG upgrade and treatment change. Patients with PTEN loss had a higher probability for protocol-based discontinuation but not for competing risk factors compared with patients with intact PTEN. Biopsy ERG status was concordant with RP TMA ERG status, while PTEN was not. Limitations include a retrospective analysis of prospective cohort data. CONCLUSIONS: PTEN status at diagnosis is a potential biomarker for identifying patients with PCa on AS with a high risk for progression or adverse findings on subsequent RP. PATIENT SUMMARY: A simple diagnostic biopsy-based analysis of PTEN status may help identify patients with high risk for prostate cancer progression.

Cumulative Cancer Locations is a Novel Metric for Predicting Active Surveillance Outcomes: A Multicenter Study.

BACKGROUND: Active surveillance (AS) of prostate cancer (PC) has increased in popularity to address overtreatment. OBJECTIVE: To determine whether a novel metric, cumulative cancer locations (CCLO), can predict AS outcomes in a group of AS patients with low and very low risk. DESIGN, SETTING, AND PARTICIPANTS: CCLO is obtained by summing the total number of histological cancer-positive locations in both diagnostic and confirmatory biopsies (Bx). The retrospective study cohort comprised three prospective AS cohorts (Helsinki University Hospital: n=316; European Institute of Oncology: n=204; and University of Münster: n=89). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analyzed whether risk stratification based on CCLO predicts different AS outcomes: protocol-based discontinuation (PBD), Gleason upgrading (GU) during AS, and adverse findings in radical prostatectomy (RP) specimens. RESULTS: In Kaplan Meier analyses, patients in the CCLO high-risk group experienced significantly shorter event-free survival for all outcomes (PBD, GU, and adverse RP findings; all p<0.002). In multivariable Cox regression analysis, patients in the CCLO high-risk group had a significantly higher risk of experiencing PBD (hazard ratio [HR] 12.15, 95% confidence interval [CI] 6.18-23.9; p<0.001), GU (HR 6.01, 95% CI 2.16-16.8; p=0.002), and adverse RP findings (HR 9.144, 95% CI 2.27-36.9; p=0.006). In receiver operating characteristic analyses, the area under the curve for CCLO outperformed the number of cancer-positive Bxs in confirmatory Bx in predicting PBD (0.734 vs 0.682), GU (0.655 vs 0.576) and adverse RP findings (0.662 vs 0.561) and the added value was supported by decision curve analysis. CONCLUSIONS: CCLO is distinct from the number of positive Bx cores. Higher CCLO predicts AS outcomes and may aid in selection of patients for AS. PATIENT SUMMARY: For patients on active surveillance for prostate cancer, the cumulative number of cancer-positive locations in diagnostic and confirmatory biopsies is a predictor of active surveillance outcomes.

Repeat multiparametric MRI in prostate cancer patients on active surveillance.

INTRODUCTION: This 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 METHODS: The 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. RESULTS: Out 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. CONCLUSION: mpMRI is a useful tool not only to select but also to monitor PCa patients on AS.

Diffusion-weighted magnetic resonance imaging in prostate cancer patients on active surveillance one year after diagnosis and before repeat biopsy.

OBJECTIVE: The aim of this study was to evaluate prospectively whether diffusion-weighted magnetic resonance imaging (DW-MRI), interpreted in a routine clinical setting, can serve as a diagnostic and prognostic tool for prostate carcinoma patients on active surveillance (AS). MATERIAL AND METHODS: Eighty men enrolled in the Finnish arm of the PRIAS (Prostate Cancer Research International: Active Surveillance) study were followed for at least 1 year and had DW-MRI scans taken in addition to repeat biopsy. Spearman's correlations were analysed between tumour appearance on DW-MRI and clinical variables [age, prostate-specific antigen (PSA), free PSA, PSA doubling time, prostate volume, percentage of cancer at diagnostic biopsy]. The Pearson chi-squared test clarified associations between outcome factors (number of positive cores and Gleason score on repeat biopsy, treatment change) and DW-MRI results. Assumed predictors of deferred radical treatment were examined with logistic regression analysis. Accuracy of tumour localization by DW-MRI compared to repeat biopsy findings was analysed by the chi-squared test. RESULTS: DW-MRI revealed an anatomical lesion suggestive of cancer in 40 patients (50%). MRI positivity showed no significant correlation with clinical variables. No associations existed between tumour appearance on DW-MRI and biopsy findings or discontinuation of AS. The only variable predicting treatment change was higher PSA at discontinuation (p = 0.002). Appearance of tumour, either on T2-weighted MRI (p = 0.273) or on apparent diffusion coefficient maps (p = 0.691), was not a significant predictor of treatment change. CONCLUSIONS: 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.