Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Population-based randomized trial of screening for clinically significant prostate cancer ProScreen: a pilot study.

OBJECTIVES: To evaluate the feasibility of a population-based screening trial using prostate-specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit. PATIENTS AND METHODS: Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score 3-5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies. RESULTS: Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA-positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]-positive) had a suspicious MRI finding (PI-RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%. CONCLUSION: The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal.

Recovery of urinary function after radical prostatectomy: predictors of urinary function on preoperative prostate magnetic resonance imaging.

PURPOSE: We determined whether pelvic soft tissue and bony dimensions on endorectal magnetic resonance imaging influence the recovery of continence after radical prostatectomy, and whether adding significant magnetic resonance imaging variables to a statistical model improves the prediction of continence recovery. MATERIALS AND METHODS: Between 2001 and 2004, 967 men undergoing radical prostatectomy underwent preoperative magnetic resonance imaging. Soft tissue and bony dimensions were retrospectively measured by 2 raters blinded to clinical and pathological data. Patients who received neoadjuvant therapy, who were preoperatively incontinent or had missing followup for continence were excluded from study, leaving 600 patients eligible for analysis. No pad use defined continent. Logistic regression was used to identify variables associated with continence recovery at 6 and 12 months. We evaluated whether the predictive accuracy of a base model was improved by adding independently significant magnetic resonance imaging variables. RESULTS: Urethral length and urethral volume were significantly associated with the recovery of continence at 6 and 12 months. Larger inner and outer levator distances were significantly associated with a decreased probability of regaining continence at 6 or 12 months, but they did not reach statistical significance for other points. Addition of these 4 magnetic resonance imaging variables to a base model including age, clinical stage, prostate specific antigen and comorbidities marginally improved the discrimination (12-month AUC improved from 0.587 to 0.634). CONCLUSIONS: Membranous urethral length, urethral volume, and an anatomically close relation between the levator muscle and membranous urethra on preoperative magnetic resonance imaging are independent predictors of continence recovery after radical prostatectomy. The addition of magnetic resonance imaging variables to a base model improved the predictive accuracy for continence recovery, but the predictive accuracy remains low.

Clinical and histopathological characteristics of familial prostate cancer in Finland.

OBJECTIVE: • To describe clinical and histopathological characteristics of Finnish familial prostate cancer (PCa) through a detailed analysis of cases in families. PATIENTS AND METHODS: • In total, 202 Finnish families with 617 histopathologically confirmed PCa cases of confirmed genealogy were collected. • Complete clinical data, including age and prostate-specific antigen (PSA) at diagnosis, stage, grade and primary treatment, were gathered. The mean (range) number of affected men per family was 3 (2-8). • All the available diagnostic biopsy samples (n= 323) were collected and regraded by the same uropathologist. • A population-based cohort of 3011 hospital district Pirkanmaa PCa patients was used as a control group. RESULTS: • The mean (range) year of diagnosis of PCa was 1993 (1962-2006) and the mean (range) age at diagnosis was 68 (43-98 years). • The median (range) primary PSA level was 12.0 (0.8-11 000) ng/mL. After regrading, the Gleason score was ≤6 in 38%, 7 in 37% and ≥8 in 25% of men. • The subset of familial PCa men diagnosed after 1995 had higher PSA levels (P= 9.9 × 10(-6) ) and an earlier age of onset (P= 1.7 × 10(-6) ) than men in the control group, although there were no differences in cancer-specific survival. CONCLUSIONS: • We observed an earlier age of onset and higher PSA in familial PCa. • However, differences between sporadic and familial or hereditary PCa cannot be truly solved until genetic testing of high-risk genes in addition to family history is used to define PCa families. • We also emphasize that, when histological samples are collected over a longer study period, reanalysis of the samples by the same experienced uropathologist should be considered.

Do pelvic dimensions and prostate location contribute to the risk of experiencing complications after radical prostatectomy?

OBJECTIVE: To assess if pelvic size, such as a narrow, steep pelvis, as well as prostate location in relation to the pelvic anatomy might have an impact on the likelihood of experiencing complications after radical prostatectomy. PATIENTS AND METHODS: In a standardized manner, different bony and soft tissue dimensions on preoperative staging MRI were retrospectively measured in a study cohort of 934 patients undergoing radical prostatectomy. Measurements were defined aimed at assessing pelvic size and prostate location. Medical and surgical complications after radical prostatectomy were meticulously reviewed and grouped into subcategories to assess whether a narrow, steep pelvis and an anatomically deeply situated prostate (which is thought to be more surgically challenging) might be associated with a higher likelihood of postoperative complications. Multivariate Cox regression was performed to assess if dimensions have a significant impact on the likelihood of postoperative complications. RESULTS: While known parameters such as a higher preoperative PSA and presence of comorbidities were associated with an increased risk of experiencing complications after surgical treatment, none of the dimensions assessed on preoperative MRI had a significant impact on the development of any medical or surgical complication. CONCLUSION: We report the largest cohort of patients where pelvic dimensions were evaluated in a standardized manner on preoperative MRI aimed at assessing anatomic factors and their impact on complications after radical prostatectomy. None of the measurements could significantly predict the likelihood of developing medical or surgical complications.

Pelvimetric dimensions do not impact upon nerve sparing or erectile function recovery in patients undergoing radical retropubic prostatectomy.

INTRODUCTION: The impact of unfavorable pelvic anatomy on the likelihood of having a nerve sparing radical retropubic prostatectomy (RRP) and the potential correlation between pelvic dimensions and recovery of erectile function (EF) after RRP have not been previously evaluated. AIM: To determine the impact of different pelvic bony and soft tissue dimensions as well as apical prostate depth on the likelihood of performing bilateral nerve sparing and on recovery of EF after RP. METHODS: Between November 2001 and June 2007, 644 potent men undergoing RRP had preoperative MRI where pelvimetry was performed with bilateral nerve sparing in 504 men. Outcomes including varying degrees of recovery of EF (level 1: normal; level 2: partial erections routinely sufficient for intercourse; level 3: partial erections occasionally sufficient for intercourse) were assessed. Median follow-up was 44.1 (interquartile range: 29.2, 65.3) months. We evaluated independent predictors of performing a bilateral nerve sparing procedure and of recovery of EF using multivariable Cox proportional hazards methods. MAIN OUTCOME MEASURES: Likelihood of performing bilateral nerve sparing as well as recovery of EF after RRP. RESULTS: Patients with higher clinical stage and biopsy Gleason score are less likely to undergo bilateral nerve sparing. Surgeon is also a factor in the likelihood of having bilateral nerve sparing RRP. On multivariate Cox regression analysis, factors predictive of recovery of EF were age, pretreatment erectile function, surgeon, and modified Charlson score. None of the pelvimetric dimensions were significant predictors of any degree of recovery of EF. However, the study is limited by its retrospective nature and by being based on MRI evaluations useful for cancer staging rather than anatomical evaluation of pelvimetric dimensions. CONCLUSIONS: We did not find unfavorable pelvic anatomy to impact the likelihood of performing a nerve sparing procedure or to be predictive of any degree of recovery of EF after RRP.

Mobile PSA: A Novel Telehealth Tool for Prostate Cancer Follow-Up.

The prevalence of prostate cancer (PCa) is increasing. As the prognosis of PCa continues to improve, the increasing follow-up requirements after radical prostatectomy or radiotherapy puts significant pressure on health care systems. Follow-up is typically conducted by treating urologists, specialized nurses, or general practitioners. Despite the increase in patient numbers, resources are not likely to increase in proportion. Furthermore, the ongoing COVID-19 pandemic has led to a paradigm shift in our thinking towards telehealth solutions, primarily to avoid or limit physical contact and to spare resources. Here we report our novel telehealth solution for PCa follow-up, called Mobile PSA. Currently, more than 4500 PCa patients have been using Mobile PSA follow-up in our center. Mobile PSA can increase follow-up accuracy, as all biochemical relapses will be detected in a timely manner, can significantly reduce delays in reporting prostate-specific antigen results to patients, and can significantly reduce costs. PATIENT SUMMARY: We assessed a new telehealth information system for prostate cancer follow-up that does not use an app. More than 4500 prostate cancer patients in our center have used this system, called Mobile PSA, for follow-up. The system significantly reduces delays in reporting prostate-specific antigen (PSA) test results to patients, increases the accuracy of detecting recurrence of elevated PSA, and reduces costs.

Associations of PTEN and ERG with Magnetic Resonance Imaging Visibility and Assessment of Non-organ-confined Pathology and Biochemical Recurrence After Radical Prostatectomy.

BACKGROUND: Diagnosing clinically significant prostate cancer (PCa) is challenging, but may be facilitated by biomarkers and multiparametric magnetic resonance imaging (MRI). OBJECTIVE: To determine the association between biomarkers phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) with visible and invisible PCa lesions in MRI, and to predict biochemical recurrence (BCR) and non-organ-confined (non-OC) PCa by integrating clinical, MRI, and biomarker-related data. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of a population-based cohort of men with PCa, who underwent preoperative MRI followed by radical prostatectomy (RP) during 2014-2015 in Helsinki University Hospital (n = 346), was conducted. A tissue microarray corresponding to the MRI-visible and MRI-invisible lesions in RP specimens was constructed and stained for PTEN and ERG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations of PTEN and ERG with MRI-visible and MRI-invisible lesions were examined (Pearson's χ2 test), and predictions of non-OC disease together with clinical and MRI parameters were determined (area under the receiver operating characteristic curve and logistic regression analyses). BCR prediction was analyzed by Kaplan-Meier and Cox proportional hazard analyses. RESULTS AND LIMITATIONS: Patients with MRI-invisible lesions (n = 35) had less PTEN loss and ERG-positive expression compared with patients (n = 90) with MRI-visible lesions (17.2% vs 43.3% [p = 0.006]; 8.6% vs 20.0% [p = 0.125]). Patients with invisible lesions had better, but not statistically significantly improved, BCR-free survival probability in Kaplan-Meier analyses (p = 0.055). Rates of BCR (5.7% vs 21.1%; p = 0.039), extraprostatic extension (11.4% vs 44.6%; p < 0.001), seminal vesicle invasion (0% vs 21.1%; p = 0.003), and lymph node metastasis (0% vs 12.2%; p = 0.033) differed between the groups in favor of patients with MRI-invisible lesions. Biomarkers had no independent role in predicting non-OC disease or BCR. The short follow-up period was a limitation. CONCLUSIONS: PTEN loss, BCR, and non-OC RP findings were more often encountered with MRI-visible lesions. PATIENT SUMMARY: Magnetic resonance imaging (MRI) of the prostate misses some cancer lesions. MRI-invisible lesions seem to be less aggressive than MRI-visible lesions.

Oncolytic Adenovirus Type 3 Coding for CD40L Facilitates Dendritic Cell Therapy of Prostate Cancer in Humanized Mice and Patient Samples.

Dendritic cell (DC)-based vaccines have shown some degree of success for the treatment of prostate cancer (PC). However, the highly immunosuppressive tumor microenvironment leads to DC dysfunction, which has limited the effectiveness of these vaccines. We hypothesized that use of a fully serotype 3 oncolytic adenovirus (Ad3-hTERT-CMV-hCD40L; TILT-234) could stimulate DCs in the prostate tumor microenvironment by expressing CD40L. Activated DCs would then activate cytotoxic T cells against the tumor, resulting in therapeutic immune responses. Oncolytic cell killing due to cancer cell-specific virus replication adds to antitumor effects but also enhances the immunological effect by releasing tumor epitopes for sampling by DC, in the presence of danger signals. In this study, we evaluated the companion effect of Ad3-hTERT-CMV-hCD40L and DC-therapy in a humanized mouse model and PC histocultures. Treatment with Ad3-hTERT-CMV-hCD40L and DC resulted in enhanced antitumor responses in vivo. Treatment of established histocultures with Ad3-hTERT-CMV-hCD40L induced DC maturation and notable increase in proinflammatory cytokines. In conclusion, Ad3-hTERT-CMV-hCD40L is able to modulate an immunosuppressive prostate tumor microenvironment and improve the effectiveness of DC vaccination in PC models and patient histocultures, setting the stage for clinical translation.

The depth of the prostatic apex is an independent predictor of positive apical margins at radical prostatectomy.

OBJECTIVE: To determine the effect of a deep and narrow pelvis on apical positive surgical margins (PSM) at radical prostatectomy (RP), controlling for other clinical and pathological variables and surgical approach, i.e. open retropubic (RRP) vs laparoscopic (LRP), as apical dissection is expected to be more challenging at RP with a prostate situated deep in a narrow pelvis. PATIENTS AND METHODS: From July 2003 to January 2005, 512 consecutive patients with preoperative prostate magnetic resonance imaging (MRI) underwent RRP or LRP with no previous radio- or hormonal therapy. An additional 74 patients with preoperative MRI undergoing RP from December 2001 to June 2007 who had an apical PSM were also included, with 586 patients comprising the study population. Bony and soft-tissue pelvic dimensions, including interspinous distance (ISD), bony (BFW) and soft tissue (SW) pelvic width, apical prostate depth (AD) and symphysis pubis angle, were measured on preoperative MRI. The pelvic dimension index (PDI), bony width index (BWI) and soft-tissue width index (SWI) were defined as ISD/AD, BFW/AD and SW/AD, respectively. Multivariate logistic regression was used to assess the effect of pelvic dimensions on apical PSM, controlling for surgical approach and clinical and pathological variables. RESULTS: There was no significant difference in ISD, BFW, SW or symphysis angle between patients with and without apical PSM. The AD was significantly greater in men with an apical PSM and consequently PDI, BWI and SWI were significantly lower in men with an apical PSM. Each of PDI, AD, BWI and SWI was a significant independent predictor of apical PSM, independent of surgical approach, and other clinicopathological variables. The main limitations of the study were that it was retrospective, and the relatively few patients with apical PSM. CONCLUSIONS: Apical prostate depth is an independent risk factor for apical PSM at RP. MRI pelvimetry might allow for preoperative planning of the approach to RP.

Fast prostate retrieval in robot-assisted laparoscopic prostatectomy for next-generation biobanking.

Robotic-assisted laparoscopic radical prostatectomy (RALP) has become the most widespread treatment for organ-confined prostate cancer. Here, we describe a fast specimen retrieval technique for RALP to obtain high-quality tissue specimen with minimal warm ischemia time for next-generation biobanking. Here, we show that using fast retrieval technique, short warm ischemia times can be achieved while not increasing the surgical time. Patients undergoing RALP with written informed consent participated in Helsinki Urological Bank study. Previously operated RALP patients and those, who were not willing to participate in the study, served as a control group. The study consisted of 1685 patients, 684 in fast retrieval and 1001 in control group. We developed a novel fast retrieval technique in which fascia is opened for camera port according to the prostate size and a running suture is placed and tightened against the camera port in the beginning of the operation. Immediately after prostate is freed from attachments, suture is loosened and the prostate is extirpated inside the endoscopic bag through the camera port fascial opening, then the fascial suture is again tightened against the camera port and the RALP procedure is completed. The mean warm ischemia times in fast retrieval group were 20 min 18 s and 22 min 30 s, respectively, in patients without and with lymphadenectomy. The mean console and surgery times with and without lymphadenectomy were similar in both groups. There were no technique-related complications associated with Fast Retrieval procedure. Tissue integrity test results for the RNA and DNA quality showed good quality for the specimen. Fast retrieval technique can easily and safely be utilized to maximize usefulness of RALP tissue specimen in downstream biobank applications.

Prostate MRI added to CAPRA, MSKCC and Partin cancer nomograms significantly enhances the prediction of adverse findings and biochemical recurrence after radical prostatectomy.

BACKGROUND: To determine the added value of preoperative prostate multiparametric MRI (mpMRI) supplementary to clinical variables and their role in predicting post prostatectomy adverse findings and biochemically recurrent cancer (BCR). METHODS: All consecutive patients treated at HUS Helsinki University Hospital with robot assisted radical prostatectomy (RALP) between 2014 and 2015 were included in the analysis. The mpMRI data, clinical variables, histopathological characteristics, and follow-up information were collected. Study end-points were adverse RALP findings: extraprostatic extension, seminal vesicle invasion, lymph node involvement, and BCR. The Memorial Sloan Kettering Cancer Center (MSKCC) nomogram, Cancer of the Prostate Risk Assessment (CAPRA) score and the Partin score were combined with any adverse findings at mpMRI. Predictive accuracy for adverse RALP findings by the regression models was estimated before and after the addition of MRI results. Logistic regression, area under curve (AUC), decision curve analyses, Kaplan-Meier survival curves and Cox proportional hazard models were used. RESULTS: Preoperative mpMRI data from 387 patients were available for analysis. Clinical variables alone, MSKCC nomogram or Partin tables were outperformed by models with mpMRI for the prediction of any adverse finding at RP. AUC for clinical parameters versus clinical parameters and mpMRI variables were 0.77 versus 0.82 for any adverse finding. For MSKCC nomogram versus MSKCC nomogram and mpMRI variables the AUCs were 0.71 and 0.78 for any adverse finding. For Partin tables versus Partin tables and mpMRI variables the AUCs were 0.62 and 0.73 for any adverse finding. In survival analysis, mpMRI-projected adverse RP findings stratify CAPRA and MSKCC high-risk patients into groups with distinct probability for BCR. CONCLUSIONS: Preoperative mpMRI improves the predictive value of commonly used clinical variables for pathological stage at RP and time to BCR. mpMRI is available for risk stratification prebiopsy, and should be considered as additional source of information to the standard predictive nomograms.

Early prostate-specific antigen changes and the diagnosis and prognosis of prostate cancer.

PURPOSE OF REVIEW: To delineate how recent findings on prostate-specific antigen (PSA) can improve prediction of risk, detection, and prediction of clinical endpoints of prostate cancer (PCa). RECENT FINDINGS: The widely used PSA cut-point of 4.0 ng/ml increasingly appears arbitrary, but no cut-point achieves both high sensitivity and high specificity. The accuracy of detecting PCa can be increased by additional predictive factors and a combinations of markers. Evidence implies that a panel of kallikrein markers improves the specificity and reduces costs by eliminating unnecessary biopsies. Large, population-based studies have provided evidence that PSA can be used to predict PCa risk many years in advance, improve treatment selection and patient care, and predict the risk of complications and disease recurrence. However, definitive evidence is currently lacking as to whether PSA screening lowers PCa -specific mortality. SUMMARY: PSA is still the main tool for early detection, risk stratification, and monitoring of PCa. However, PSA values are affected by many technical and biological factors. Instead of using a fixed PSA cut-point, using statistical prediction models and considering the integration additional markers may be able to improve and individualize PCa diagnostics. A single PSA measurement at early middle age can predict risk of advanced PCa decades in advance and stratify patients for intensity of subsequent screening.

PALB2 variants in hereditary and unselected Finnish prostate cancer cases.

BACKGROUND: PALB2 1592delT mutation is associated with increased breast cancer and suggestive prostate cancer (PRCA) risk in Finland. In this study we wanted to assess if any other PALB2 variants associate to increased PRCA risk and clinically describe patients with formerly found PALB2 1592delT mutation. METHODS: Finnish families with two or more PRCA cases (n = 178) and unselected cases (n = 285) with complete clinical data were initially screened for variants in the coding region and splice sites of PALB2. Potentially interesting variants were verified in additional set of unselected cases (n = 463). RESULTS: From our clinically defined sample set we identified total of six variants in PALB2. No novel variants among Finnish PRCA cases were found. Clinical characteristics of the variant carriers, including the previously described family carrying PALB2 1592delT, revealed a trend towards aggressive disease, which also applied to a few non-familial cases. Hypersensitivity to mitomycin C (MMC) of lymphoblasts from individuals from the family with 1592delT revealed haploinsufficiency among carriers with altered genotype. CONCLUSIONS: Though any of the detected PALB2 variants do not associate to PRCA in population level in Finland it cannot be ruled out that some of these variants contribute to cancer susceptibility at individual level.

Randomised Trial of Adjuvant Radiotherapy Following Radical Prostatectomy Versus Radical Prostatectomy Alone in Prostate Cancer Patients with Positive Margins or Extracapsular Extension.

BACKGROUND: It remains unclear whether patients with positive surgical margins or extracapsular extension benefit from adjuvant radiotherapy following radical prostatectomy. OBJECTIVE: To compare the effectiveness and tolerability of adjuvant radiotherapy following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: This was a randomised, open-label, parallel-group trial. A total of 250 patients were enrolled between April 2004 and October 2012 in eight Finnish hospitals, with pT2 with positive margins or pT3a, pN0, M0 cancer without seminal vesicle invasion. INTERVENTION: A total of 126 patients received adjuvant radiotherapy at 66.6Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was biochemical recurrence-free survival, which we analysed using the Kaplan-Meier method and Cox proportional hazard regression. Overall survival, cancer-specific survival, local recurrence, and adverse events were secondary endpoints. RESULTS AND LIMITATIONS: The median follow-up time for patients who were alive when the follow-up ended was 9.3yr in the adjuvant group and 8.6yr in the observation group. The 10-yr survival for biochemical recurrence was 82% in the adjuvant group and 61% in the observation group (hazard ratio [HR] 0.26 [95% confidence interval {CI} 0.14-0.48], p<0.001), and for overall survival 92% and 87%, respectively (HR 0.69 [95% CI 0.29-1.60], p=0.4). Two and four metastatic cancers occurred, respectively. Out of the 43 patients with biochemical recurrence in the observation group, 37 patients received salvage radiotherapy. In the adjuvant group, 56% experienced grade 3 adverse events, versus 40% in the observation group (p=0.016). Only one grade 4 adverse event occurred (adjuvant group). A limitation of this study was the number of patients. CONCLUSIONS: Adjuvant radiotherapy following radical prostatectomy is generally well tolerated and prolongs biochemical recurrence-free survival compared with radical prostatectomy alone in patients with positive margins or extracapsular extension. PATIENT SUMMARY: Radiotherapy given immediately after prostate cancer surgery prolongs prostate-specific antigen progression-free survival, but causes more adverse events, when compared with surgery alone.

Initiation of robot-assisted radical prostatectomies in Finland: Impact on centralization and quality of care.

Objective The aim of this study was to analyze the impact of introduction of robot-assisted prostate surgery and its quality measures in Finland from 2008 to 2012. Materials and methods Registry data were collected for time trends and national distribution of prostate cancer surgery in Finland, while preoperative, operative and follow-up data were collected for quality measures. Results The number and proportion of robot-assisted laparoscopic radical prostatectomies (RALPs) increased rapidly and they accounted for 68% of all radical prostatectomies in 2012. The number of centers performing prostatectomies diminished from 25 to 20 at the expense of low-volume centers. In total, 1996 patients were operated on in the four RALP centers in 2008-2012. As anticipated, the learning curve was uniform between the centers, as were mean blood loss (212 ml), hospitalization (1.8 days) and catheterization times (10.6 days). At 3 and 12 months, 49.4% and 71.2% of patients, respectively, were totally continent (no pads). After unilateral nerve-sparing surgery, 9.9% and 5.1% had partial or normal erection at 3 months postoperatively and 14.8% and 20.4% at 12 months, respectively. If bilateral nerve sparing was done, the figures were 13.0% and 13.5% at 3 months and 14.6% and 34.9% at 12 months. Clavien-Dindo grade 3, 4 or 5 complications were seen in 0.3%, 0.3% and 0.1% of patients, respectively. Limitations of the study include non-standardized collection of outcome parameters. Conclusions This report shows that the main impact of adoption of RALP on a national level was rapid spontaneous centralization of prostate cancer surgery. The main advantages of minimally invasive prostatectomy, i.e. low blood loss and short hospitalization, are easily achieved, while continuous effort is necessary for improvements in surgical outcomes.

Germ-line alterations in MSR1 gene and prostate cancer risk.

PURPOSE: The MSR1 gene maps to 8p22-23, a novel susceptibility locus for hereditary prostate cancer (HPC). Mutations in MSR1 have been reported to associate with prostate cancer (PRCA) risk. Here we report a follow-up study from Finland to evaluate the association between PRCA and MSR1 gene. EXPERIMENTAL DESIGN: The youngest affected patient from each of 120 HPC families was initially used for the screening of MSR1 mutations by single-strand conformational polymorphism analysis. Selected variants of MSR1 gene were then screened in 537 unselected PRCA cases and in 480 controls. RESULTS: Among 120 HPC families, five MSR1 sequence variants were identified. The carrier frequencies of the R293X, P275A, and -14743A>G variants were compared between the probands with HPC, unselected PRCA cases, and healthy male blood donors. No significant differences were observed. The odds ratios for R293X, P275A, and -14743A>G mutations were also calculated to estimate the PRCA risk. No significantly elevated or lowered risks for PRCA among these three variants were detected. However, the mean age at diagnosis of the R293X mutation carriers among HPC probands was significantly lower compared with noncarriers (55.4 versus 65.4 years; t test, P = 0.04). The same trend was observed among unselected PRCA cases (65.7 versus 68.7 years; t test, P = 0.37). CONCLUSIONS: Our results do not support a major role for the MSR1 gene in the causation of hereditary or unselected PRCAs but suggest a possible modifying role in cancer predisposition.

Side-fenestrated catheter decreases leakage at the urethrovesical anastomosis after robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: The aim of this study was to analyse whether a side-fenestrated urinary catheter can decrease the frequency of anastomotic leakage after robot-assisted laparoscopic radical prostatectomy (RALP). MATERIAL AND METHODS: Two-hundred and fifty patients with localized prostate cancer undergoing RALP were randomized into standard and side-fenestrated catheter groups in a prospective randomized study. The catheter was fenestrated at the site of the anastomosis to improve drainage. A cystogram was taken at 7 ± 2 days postoperatively to verify the watertightness of the anastomosis. The patients were monitored for 3 months. RESULTS: The study included 106 patients with the standard and 108 patients with the fenestrated catheter. Leakage at the urethrovesical anastomosis was found in 13/106 (12.3%) of the standard and 5/108 (4.6%) of the side-fenestrated catheter patients (p = 0.044). Discomfort induced by the catheter and urinary leakage beside the catheter did not differ between the groups. The clinical and pathological characteristics and complications were equal between the groups. CONCLUSIONS: The side-fenestrated catheter decreased leakage rates at the urethrovesical anastomosis after RALP.

Ethnic variation in pelvimetric measures and its impact on positive surgical margins at radical prostatectomy.

OBJECTIVES: We sought to evaluate the ethnic variation in pelvimetry and its impact as a predictor of positive surgical margins (PSM) at radical prostatectomy (RP). METHODS: Preoperative MRI was performed in 482 Caucasian and 103 African American (AA) men undergoing RP without previous treatment from July 2003 to January 2005 and November 2001 to June 2007, respectively. We measured bony and soft tissue dimensions on magnetic resonance imaging (MRI) to evaluate the pelvic inlet, midplane, prostate size, and apical depth. Analysis of covariance was performed to determine the effect of ethnicity on the midpelvic area (MPA). We performed multivariate logistic regression analysis for prediction of overall and site-specific PSM. RESULTS: AA men had a significantly steeper symphysis pubis angle (median, 43.1 vs. 41.3°, respectively, P = .001) and smaller MPA (median, 78.5 vs. 83.9 cm(2), respectively, P = .004). Ethnicity and BMI were found to have a significant effect on MPA. Apical depth of the prostate was identified as a significant independent predictor of apical PSM, with a more pronounced effect in AA men. Pelvimetric measures were not a significant predictor of other sites of PSM. CONCLUSIONS: AA men have a significantly smaller MPA and steeper symphysis angle. The adverse impact of a deep pelvis, as measured by the apical prostatic depth on apical PSM was found to be greater in AA men. Evaluation of pelvic dimensions and prostate parameters in preoperative MRI may add to our understanding of their impact on surgical outcomes.

Incidence of cancer in finnish families with clinically aggressive and nonaggressive prostate cancer.

BACKGROUND: Clinical features of familial prostate cancer (PCa) and other malignancies associated with PCa are poorly described. Using a large family-based data registry of histologically confirmed cancers with a 40-year follow-up, we sought to determine incidence of cancer in Finnish PCa families, separately for clinically aggressive and clinically nonaggressive PCa. METHODS: We calculated standardized incidence ratios (SIR) for 5,523 members of 202 families by dividing the number of observed cancers (altogether 497 cases) by the number of expected cancers. The number of expected cancers is based on the national cancer incidence rates. RESULTS: SIR for overall cancer risk, excluding PCa, for male relatives in clinically nonaggressive families was 0.7 [95% confidence interval (95% CI), 0.6-0.8] and in clinically aggressive families 0.8 (95% CI, 0.6-1.0). The respective SIRs for women were 1.0 (95% CI, 0.8-1.1) and 1.1 (95% CI, 0.8-1.3). The incidence of lung cancer among men was significantly lower than in the general population. The SIR for gastric cancer among women was 1.9 in both clinically nonaggressive and clinically aggressive families. In clinically aggressive families, there was borderline significant excess of cancer of the gallbladder in men and liver cancer in women. CONCLUSIONS: The incidence of non-PCa cancers is not increased in clinically aggressive or clinically nonaggressive PCa families except for stomach cancer among women.