A prospective case series to evaluate subcostal nerve injury with high-resolution ultrasound in posterior retroperitoneoscopic adrenalectomy.

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy has several advantages over transabdominal laparoscopic adrenalectomy regarding operating time, blood loss, postoperative pain, and recovery. However, postoperatively several patients report chronic pain or hypoesthesia. We hypothesized that these symptoms may be the result of damage to the subcostal nerve, because it passes the surgical area. METHODS: A prospective single-center case series was performed in adult patients without preoperative pain or numbness of the abdominal wall who underwent unilateral posterior retroperitoneoscopic adrenalectomy. Patients received pre- and postoperative questionnaires and a high-resolution ultrasound scan of the subcostal nerve and abdominal wall muscles was performed before and directly after surgery. Clinical evaluation at 6 weeks was performed with repeat questionnaires, physical examination, and high-resolution ultrasound. Long-term recovery was evaluated with questionnaires, and photographs from the patients were examined for abdominal wall asymmetry. RESULTS: A total of 25 patients were included in the study. There were no surgical complications. Preoperative visualization of the subcostal nerve was possible in all patients. At 6 weeks, ultrasound showed nerve damage in 15 patients, with no significant association between nerve damage and postsurgical pain. However, there was a significant association between nerve damage and hypoesthesia (p = 0.01), sensory (p < 0.001), and motor (p < 0.001) dysfunction on physical examination. After a median follow-up of 18 months, 5 patients still experienced either numbness or muscle weakness, and one patient experienced chronic postsurgical pain. CONCLUSION: In this exporatory case series the incidence of postoperative damage to the subcostal nerve, both clinically and radiologically, was 60% after posterior retroperitoneoscopic adrenalectomy. There was no association with pain, and the spontaneous recovery rate was high.

Adrenal fast-track and enhanced recovery in retroperitoneoscopic surgery for primary aldosteronism improving patient outcome and efficiency.

PURPOSE: No data exist on perioperative strategies for enhancing recovery after posterior retroperitoneoscopic adrenalectomy (PRA). Our objective was to determine whether a multimodality adrenal fast-track and enhanced recovery (AFTER) protocol for PRA can reduce recovery time, improve patient satisfaction and maintain safety. METHODS: Thirty primary aldosteronism patients were included. Fifteen patients were treated with 'standard-of-care' PRA and compared with 15 in the AFTER protocol. The AFTER protocol contains: a preoperative information video, postoperative oral analgesics, early postoperative mobilisation and enteral feeding, and blood pressure monitoring at home. The primary outcome was recovery time. Secondary outcomes were length of hospital stay, postoperative pain and analgesics requirements, patient satisfaction, perioperative complications and quality of life (QoL). RESULTS: Recovery time was much shorter in both groups than anticipated and was not significantly different (median 28 days). Postoperative length of hospital stay was significantly reduced in AFTER patients (mean 32 vs 42 h, CI 95%, p = 0.004). No significant differences were seen in pain, but less analgesics were used in the AFTER group. Satisfaction improved amongst AFTER patients for time of admission and postoperative visit to the outpatient clinic. There were no significant differences in complication rates or QoL. CONCLUSION: Despite no difference in recovery time between the two groups, probably due to small sample size, the AFTER protocol led to shorter hospital stays and less analgesic use after surgery, whilst maintaining and even enhancing patient satisfaction for several aspects of perioperative care. Complication rates and QoL are comparable to standard-of-care.

Percutaneous Nephrolithotomy with Intraoperative Computed Tomography Scanning Improves Stone-Free Rates.

Introduction: The use of fluoroscopy during percutaneous nephrolithotomy (PCNL) may lead to an overestimation of stone-free rates. The objective of this study is to demonstrate the feasibility of intraoperative CT-guided PCNL compared with standard of care (SoC) PCNL. Patients and Methods: A prospective feasibility study (20 patients undergoing PCNL with an intraoperative CT scan between June 2017 and February 2020) and a retrospective study of a historical cohort (20 consecutive patients undergoing SoC PCNL between September 2015 and September 2016) were conducted. All procedures were performed by an expert endourologist in a tertiary referral hospital. Follow-up was performed at 6 weeks postoperatively. The primary goal is to investigate the practicality and potential benefits and harms of intraoperative CT scanning during PCNL. Secondary outcomes are a stone-free rate after the 6-week follow-up, perioperative radiation exposure, the need for postoperative imaging, and peri- and postoperative complications. Statistical significance was considered at p < 0.05. Results: The initial stone-free rate in the CT scan group was 65% (n = 13). In 25% (n = 5) of patients, residual stone fragments were removed after the perioperative CT scan. In the SoC group, 85% (n = 17) of patients were thought to be stone free perioperatively. At the 6-week follow-up, 80% (n = 16) in the CT scan group vs 50% in the SoC group (n = 10) were found to be stone free. Radiation exposure, perioperatively, was higher in the CT scan group. Complications were comparable between groups. Limitations of the study are the nonrandomized design of the study and nonstandardized follow-up imaging. Conclusions: Intraoperative CT scanning during PCNL is feasible and gives a better estimate of any remaining stone fragments compared with fluoroscopy only.

Complete remission of nephrotic syndrome in a young woman with anti-LRP2 nephropathy after immunosuppressive therapy.

BACKGROUND: Anti-low density lipoprotein receptor-related protein 2 (LRP2) nephropathy/anti-brush border antibody (ABBA) disease is a disorder characterized by acute tubulointerstitial injury associated with circulating antibodies to kidney proximal tubular brush border protein LRP2/megalin. Patients are typically elderly and present with acute kidney injury and subnephrotic proteinuria. They progress to end-stage renal disease with poor response to immunosuppressive therapies. CASE PRESENTATION: We report a case of a 29-year-old Chinese woman, who presented with nephrotic syndrome with normal kidney function. Kidney biopsy showed no obvious tubular injury or interstitial inflammation. Positive immunoglobulin G (IgG) staining was revealed along the brush border of proximal tubular cells. Anti-LRP2 antibody was identified in serum, consistent with a diagnosis of anti-LRP2 nephropathy. The patient achieved complete remission after receiving prednisone and cyclophosphamide. CONCLUSIONS: Anti-LRP2 nephropathy can also present as nephrotic syndrome in young patients and complete remission from nephrotic syndrome may be achieved after immunosuppressive therapy.

The Utility of Rise in Red Cell Distribution Width in Determining the Risk of Renal Relapse in Lupus Nephritis.

BACKGROUND: We hypothesized that the levels of red cell distribution width (RDW) would correlate with lupus nephritis (LN) disease activity, therapeutic response after induction therapy, and its rise would be associated with future renal relapse in patients who had achieved clinical remission. METHODS: The associations of RDW and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal response, and renal relapse after induction therapy were examined in 172 biopsy-proven LN patients at the Division of Nephrology, Huashan Hospital Fudan University between 2007 and 2017. RESULTS: The median RDW of LN patients was significantly higher than that of healthy individuals (p < 0.001). Baseline RDW demonstrated positive correlation with baseline SLEDAI (r = 0.239, p = 0.004). Overall RDW after induction treatment was significantly decreased (p = 0.005), especially in the complete remission (CR) group (p = 0.02), and the partial remission (PR) group had a decreasing trend (p = 0.09), while the change of RDW in the no response (NR) group was not statistically significant (p = 0.70). Among the 153 patients who achieved remission after induction therapies, 37 (24.2%) patients developed 42 episodes of subsequent renal flare during a median follow-up of 36.0 (IQR, 20 - 66) months. The median time from remission to renal flare was 18.0 (IQR, 7.0 - 45.0) months. The overall renal flare rate was 0.065 relapse per patient-year. During follow up, 54 RDW rises (defined as more than 0.5% increase in RDW) were identified. There were 33 episodes (61.1%) of renal flares in patients with RDW rises, while there were only 9 renal flares (8.65%) in 104 patients without RDW rise (p < 0.001). Survival analysis showed that RDW rise was associated with a significantly higher risk of future renal relapse (adjusted HR, 14.03; 95% CI, 5.29 to 37.20; p < 0.001). CONCLUSIONS: In addition to correlating with disease activity and therapeutic response to induction therapy in patients with LN, RDW rise is a significant predictor of future renal relapse in patients who achieve remission.

An Update on Early Urological Complications in Kidney Transplantation: A National Cohort Study.

BACKGROUND This study aimed to provide an update on the occurrence of early urological complications in living-donor and deceased-donor kidney transplantation (KTX). MATERIAL AND METHODS Data on all kidney transplant recipients in the Netherlands between January 2005 and December 2015 were retrieved from the prospectively collected Dutch National Organ Transplant Registry Database (NOTR). We assessed the incidence of major urological complications (MUCs) within 3 months after KTX, defined as urinary leakage and ureteral obstruction. Outcomes of living donor and deceased donor kidney transplants were compared. We performed regression analysis to identify predictive factors of urological complications and studied the influence of early urological complications on graft and patient survival. We performed an additional sub-study to explore the influence of preservation of the peri-ureteric connective tissue in living-donor KTX on the occurrence of urological complications. RESULTS Among 3329 kidney transplant recipients, urological complications occurred in 208 patients (6.2%) within 3 months after surgery. There were no significant differences in complication rates between recipients from living donors and deceased donors. Multiple regression analysis showed that older donor age and previous cardiac events of the recipient were predictors for the development of urological complications. Graft and patient survival were not affected by early MUCs. The additional sub-study showed that preservation of peri-ureteric tissue within living-donor KTX was not independently associated with urological complications. CONCLUSIONS Many living- and deceased-donor KTX recipients have early urological complications. MUCs did not affect long-term graft or patient survival.

The complete mitochondrial genome of the cigarette beetle, Lasioderma serricorne (Coleoptera: Anobiidae).

The cigarette beetle, Lasioderma serricorne (Fabricius), is an important pest of stored commodities and distributed widely in the world. Here, we report the complete mitochondrial genome of L. serricorne which was 15,958 bp and composed of 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and a control region. The gene order and orientation of L. serricorne were identical to those of other Coleopteran mitogenomes. ATG, ATA, ATT, ATC, TTG were initiation codons and TAA, TAG, T were termination codons. All 22 tRNA genes were predicted with a typical cloverleaf structure except for trnS1 (AGN). Phylogenetic analysis performed using 13 PCGs with 14 other beetles showed that L. serricorne is closely related to Stegobium paniceum, which agree with the conventional taxonomy.

Renal phospholipase A2 receptor in hepatitis B virus-associated membranous nephropathy.

OBJECTIVE: This study examined the expression of renal phospholipase A2 receptor (PLA2R) in idiopathic and secondary membranous nephropathy (MN). METHODS: Patients with biopsy-proven MN and non-MN were enrolled. Renal PLA2R was examined using an anti-PLA2R antibody (anti-PLA2R-Ab), and circulating PLA2R-Ab was detected by indirect immunofluorescence. RESULTS: Renal PLA2R was detected along the capillary loop in 84% patients with idiopathic MN but not in those with any other primary glomerulonephritis. Only 1 of 38 patients with class V lupus nephritis showed renal PLA2R positive. In hepatitis B virus-associated MN (HBV-MN), 64% showed renal PLA2R positive, and PLA2R overlapped with HBsAg along the capillary loop. In addition, renal PLA2R positivity was closely associated with serum PLA2R-Ab. Renal PLA2R positive was present in all the patients with serum PLA2R-Ab positive and in 53% of patients with serum PLA2R-Ab negative. However, in patients with renal PLA2R negative, serum PLA2R-Ab was all negative. CONCLUSION: Renal biopsy PLA2R positivity was common in idiopathic MN and HBV-MN but rare in lupus-associated MN, and it was closely associated with serum PLA2R-Ab production. Further studies examining the association between PLA2R and HBV-MN may shed light on the mechanism of idiopathic MN or HBV-MN. © 2015 S. Karger AG, Basel.

Overestimation of prostate cancer mortality and other-cause mortality by the Kaplan-Meier method.

INTRODUCTION: To assess the extent of overestimation of the cumulative probability of death by the Kaplan-Meier method with the competing-risks regression analysis as reference approach. MATERIALS AND METHODS: Data were derived from the screening arm of the Rotterdam branch of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The screening arm consisted of 21210 men between the ages of 55 and 74 at study entry. Follow up concerning mortality was complete through 2008. Endpoints were 5 and 10 year cumulative probabilities of prostate cancer death and death from other causes. Relative bias was defined as the ratio of the cumulative probability of death as determined by the Kaplan-Meier method, relative to the cumulative probability obtained by the competing-risks analysis. RESULTS: According to the Kaplan-Meier method, the 5 year cumulative probability of death from prostate cancer was 0.0101, compared with 0.0099 according to the competing-risk analysis [1.8% overestimation]. At 10 year, these numbers were 0.0347 and 0.0321, respectively [8.0% overestimation]. For death from other causes, the cumulative probabilities at 5 year were 0.0399 and 0.0397 according to the Kaplan-Meier and the competing-risks method [0.6% overestimation], respectively. At 10 year, the probabilities were 0.141 and 0.139 [1.7% overestimation], respectively. CONCLUSIONS: When competing events are present, the competing-risks regression analysis is to be preferred over the Kaplan-Meier method in the estimation of the cumulative probability of the event of interest.

Outcomes of a bladder cancer screening program using home hematuria testing and molecular markers.

BACKGROUND: We previously reported the preliminary findings from a feasibility study of bladder cancer (BCa) screening with urinary molecular markers (Bladder Cancer Urine Marker Project [BLU-P]) that has now been terminated. OBJECTIVE: To report the final results from BLU-P to determine whether mass screening for BCa is feasible and useful. DESIGN, SETTING, AND PARTICIPANTS: BLU-P was a Dutch population-based study initiated in 2008 to evaluate BCa screening. A total of 6500 men were invited to participate in the study, 1984 (30.5%) agreed, and 1747 (88.1%) men completed the protocol and were followed for 2 yr. INTERVENTION: The screening protocol included home hematuria testing followed by molecular markers-nuclear matrix protein 22 (NMP22), microsatellite analysis (MA), fibroblast growth factor receptor 3 (FGFR3) mutation snapshot assay, and a custom methylation-specific (MLPA) test-to determine the need for cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes included the number of cystoscopies and the cancer detection rate within and outside the protocol, as determined by linkage to national registries. RESULTS AND LIMITATIONS: Overall, 409 men (23.4%) tested positive for hematuria and underwent molecular testing. Current smokers (n=295 [17%]) and past smokers (n=998 [58%]) were significantly more likely to test positive for hematuria than nonsmokers. Seventy-one of 75 men (94.6%) with positive molecular markers underwent the recommended cystoscopy. Four BCas and one kidney tumor were detected through this sequential protocol, whereas one BCa and one kidney tumor were missed through the screening program. Limitations include the possibility of healthy subject bias. CONCLUSIONS: For BCa screening, use of a sequential protocol with home hematuria testing followed by molecular markers substantially reduced the number of cystoscopy recommendations compared with dipstick testing alone. A sequential screening approach may help minimize unnecessary invasive follow-up testing, with very few missed cancers. Nevertheless, this mass screening program had a very low diagnostic yield in an unselected asymptomatic European male population.

Complications of initial prostate biopsy in a European randomized screening trial.

BACKGROUND: Transrectal prostate needle biopsy (PNB) is a standard procedure for the diagnosis of prostate cancer. We recently found an increasing frequency of hospitalization with infectious complications associated with PNB over time. OBJECTIVE: To perform an updated analysis of overall complication rates in a large screening population over the past 18 years and to examine possible predictors of complications on initial PNB. DESIGN, SETTING AND PARTICIPANTS: From 1993-2011, 7216 men underwent initial lateralized sextant PNB in European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam. After 2 weeks a questionnaire was administered to 6962 men regarding PNB-related complications. Outcome Measurements & Statistical Analysis: Overall complication rates as well as specific complications (hematuria for >3 days, hematospermia, significant pain after biopsy, fever, and hospitalizations) were prospectively recorded. Multivariable logistic regression models were performed to assess the relationship between age, comorbidities, and prostate volume with specific complications. RESULTS AND LIMITATIONS: A total of 4674 (67.1%) men reported any sequelae after initial PNB, with hematospermia as the most frequent (53.8%), followed by hematuria (24.3%). Significant pain (4.8%), fever (4.1%), and hospital admission (0.7%) were reported less frequently. Hematospermia was significantly more likely in younger men with fewer comorbidities and smaller prostate volume; whereas hematuria was significantly more frequent among men with increasing comorbidities and prostate volume. In addition, pain was inversely associated with age and was also reported less frequently during later years of biopsy. Limitations of our study include the use of sextant biopsies and a relatively healthy population, while strengths include the large sample size and data on patient-specific covariates. CONCLUSION: Many men experience minor complications after initial PNB, although the frequency of specific complications such as hematospermia and hematuria differed based upon factors such as prostate volume and comorbidities. Overall, these data are useful to counsel patients who are undergoing their first PNB on the frequency of complications in a screening population.

Active surveillance for low-risk prostate cancer worldwide: the PRIAS study.

BACKGROUND: Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa. OBJECTIVE: To update our experience in the largest worldwide prospective AS cohort. DESIGN, SETTING, AND PARTICIPANTS: Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤ 10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤ 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. RESULTS AND LIMITATIONS: In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. CONCLUSIONS: Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized. TRIAL REGISTRATION: The current program is registered at the Dutch Trial Register with ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718).

A Calculator for Prostate Cancer Risk 4 Years After an Initially Negative Screen: Findings from ERSPC Rotterdam.

BACKGROUND: Inconclusive test results often occur after prostate-specific antigen (PSA)-based screening for prostate cancer (PCa), leading to uncertainty on whether, how, and when to repeat testing. OBJECTIVE: To develop and validate a prediction tool for the risk of PCa 4 yr after an initially negative screen. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from 15 791 screen-negative men aged 55-70 yr at the initial screening round of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Follow-up and repeat screening at 4 yr showed either no PCa, low-risk PCa, or potentially high-risk PCa (defined as clinical stage >T2b and/or biopsy Gleason score ≥ 7 and/or PSA ≥ 10.0 ng/ml). A multinomial logistic regression analysis included initial screening data on age, PSA, digital rectal examination (DRE), family history, prostate volume, and having had a previous negative biopsy. The 4-yr risk predictions were validated with additional follow-up data up to 8 yr after initial screening. RESULTS AND LIMITATIONS: Positive family history and, especially, PSA level predicted PCa, whereas a previous negative biopsy or a large prostate volume reduced the likelihood of future PCa. The risk of having PCa 4 yr after an initially negative screen was 3.6% (interquartile range: 1.0-4.7%). Additional 8-yr follow-up data confirmed these predictions. Although data were based on sextant biopsies and a strict protocol-based biopsy indication, we suggest that men with a low predicted 4-yr risk (eg, ≤ 1.0%) could be rescreened at longer intervals or not at all, depending on competing risks, while men with an elevated 4-yr risk (eg, ≥ 5%) might benefit from immediate retesting. These findings need to be validated externally. CONCLUSIONS: This 4-yr future risk calculator, based on age, PSA, DRE, family history, prostate volume, and previous biopsy status, may be a promising tool for reducing uncertainty, unnecessary testing, and overdiagnosis of PCa.

Positive predictive value of prostate biopsy indicated by prostate-specific-antigen-based prostate cancer screening: trends over time in a European randomized trial*.

UNLABELLED: Study Type--Diagnosis (validating cohort) Level of Evidence 1b. What's known on the subject? and What does the study add? The European Randomized study of Screening for Prostate Cancer (ERSPC) showed a reduction in prostate cancer mortality of 21% for PSA-based screening at a median follow-up of 11 years. In the ERSPC, men are screened at 4-year intervals. A prostate biopsy is recommended for men with a PSA level ≥ 3.0 ng/mL. The study shows that the positive predictive value (PPV) of a prostate biopsy indicated by PSA-based screening remains equal throughout consecutive screening rounds in men without a previous biopsy. In men who have previously had a benign biopsy, the PPV drops considerably, but 20% of the cancers detected still show aggressive characteristics. OBJECTIVE: • To assess the positive predictive value (PPV) of prostate biopsy, indicated by a prostate-specific antigen (PSA) threshold of ≥ 3.0 ng/mL, over time, in the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC). PATIENTS AND METHODS: • In the Rotterdam section of the ERSPC, a total of 42,376 participants, aged 55-74 years, identified from population registries were randomly assigned to a screening or control arm. • For the ERSPC men undergo PSA screening at 4-year intervals. A total of three screening rounds were evaluated; therefore, only men aged 55-69 years at the first screening were eligible for the present study. RESULTS: • PPVs for men without previous biopsy remained equal throughout the three subsequent screenings (25.5, 22.3 and 24.8% respectively). • Conversely, PPVs for men with a previous negative biopsy dropped significantly (12.0 and 15.2% at the second and third screening, respectively). • Additionally, in men with and without previous biopsy, the percentage of aggressive prostate cancers (clinical stage >T2b, Gleason score ≥ 7) decreased after the first round of screening from 44.4 to 23.8% in the second (P < 0.001) and 18.6% in the third round (P < 0.001). • Repeat biopsies accounted for 24.6% of all biopsies, but yielded only 8.6% of all aggressive cancers. CONCLUSIONS: • In consecutive screening rounds the PPV of PSA-based screening remains equal in previously unbiopsied men. • In men with a previous negative biopsy the PPV drops considerably, but 20% of cancers detected still show aggressive characteristics. • Individualized screening algorithms should incorporate previous biopsy status in the decision to perform a repeat biopsy with the aim of further reducing unnecessary biopsies.

Efficacy versus effectiveness study design within the European screening trial for prostate cancer: consequences for cancer incidence, overall mortality and cancer-specific mortality.

OBJECTIVE: To assess the impact of different study designs on outcome data within the European Randomized Study of Screening for Prostate Cancer (ERSPC). METHODS: Observed data from the Gothenburg centre (effectiveness trial with upfront randomization before informed consent) and the Rotterdam centre (efficacy trial with randomization after informed consent) were compared with expected data, which were retrieved from national cancer registries and life tables. Endpoints were 11-year cumulative prostate cancer (PC) incidence, overall mortality and PC-specific mortality. RESULTS: In Gothenburg, the 11-year PC incidence was higher than predicted (5.8%) in both the intervention (12.4%) and control arms (7.3%). The observed overall mortality was higher than predicted (15.9%) in both the intervention (17.8%) and control arms (18.5%). The observed PC-specific mortality in the intervention arm was 0.56% versus 0.83% in the control arm, while the expected mortality was 0.83%. In Rotterdam, the observed PC incidence in the intervention arm (10.4%) was higher than expected (4.4%). The incidence in the control arm was 4.6%. The observed overall mortality was lower than expected: 13.6% in the intervention arm and 14.0% in the control arm versus an expected mortality of 16.1%. The observed PC-specific mortality was lower than expected (0.65%) in both the intervention (0.27%) and control arms (0.41%). CONCLUSIONS: Our results suggest that an efficacy trial with informed consent prior to randomization may have introduced a 'healthy screenee bias'. Therefore, an effectiveness trial with consent after randomization may more accurately estimate the PC-specific mortality reduction if population-based screening is introduced.

Long-term radical prostatectomy outcomes among participants from the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam.

UNLABELLED: Study Type--Therapy (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long-term outcomes among men with clinically-detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen-detected prostate cancer. OBJECTIVE: • To examine the long-term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). PATIENTS AND METHODS: • Among 42,376 men randomised during the period of the first round of the trial (1993-1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively. • Of these men, 420 (36.5%) screen-detected and 54 (25.7%) controls underwent RP with long-term follow-up data (median follow-up 9.9 years). • Progression-free (PFS), metastasis-free (MFS) and cancer-specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen-detected (vs control) was associated with RP outcomes after adjusting for standard predictors. RESULTS: • RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen-detected cases had significantly lower prostate-specific antigen (PSA) levels at diagnosis. • Men from the screening arm had a significantly higher PFS (P = 0.003), MFS (P < 0.001) and CSS (P = 0.048). • In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.83, P = 0.011) and metastasis (HR 0.18, 95% CI 0.06-0.59, P = 0.005). • Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms. • Limitations of the present study include lead-time bias and non-randomised treatment selection. CONCLUSIONS: • After RP, screen-detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow-up time. • The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables. • However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume.

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.

Increased non-prostate cancer death risk in clinically diagnosed prostate cancer.

UNLABELLED: Study Type - Prognosis (case control). Level of Evidence 3a. What's known on the subject? and What does the study add? Treatment of advanced PC might put patients at an increased risk of cardiovascular events. Recent studies have suggested that the excess mortality is lower among men who were diagnosed with screen detected PC in comparison to men with clinically diagnosed PC, possibly due to the use of medications for cardiovascular disease and the change to a healthier lifestyle of men with a screen detected PC. Men with clinically diagnosed PC have an increased risk of death unrelated to PC itself, i.e., the excess mortality is based on an increased risk of dying from other neoplasm and diseases of the circulatory or respiratory system. OBJECTIVE: • To assess the cause-specific mortality unrelated to prostate cancer (PC) itself in patients with screen- and clinically diagnosed PC. PATIENTS AND METHODS: • The present study was conducted among participants of the European Randomized Study of Screening for Prostate Cancer. • Based on consensus of the causes of death committee (CODC), all patients who died from PC were excluded. • In the intervention arm, cases were patients with a screen-detected PC, aged 55-74 years, between 1993 and 2001. • These cases were matched to two controls in whom no cancer was found after biopsy, and two controls in whom no cancer was suspected after screening. In the control arm, cases were patients with clinically diagnosed PC, aged 55-74 years, between 1993 and 2001. These cases were matched to four controls without PC. Matching was done with respect to date of birth, screening and/or diagnosis. Men were followed up to 31 December 2007. RESULTS: • No statistically significant difference in overall mortality between cases and controls in the intervention arm was observed: relative risk (RR) 1.26 (95% confidence interval [CI] 0.96-1.65; P = 0.102) and RR 1.13 (95% CI 0.86-1.47; P = 0.381). • In the control arm, the overall mortality was statistically significantly higher in cases relative to controls: RR 1.43 (95% CI 1.03-2.00; P = 0.033). • This difference was because of an increased risk of dying from neoplasms and disease of the circulatory or respiratory system among cases: RR 1.61 (95% CI 1.12-2.29; P = 0.009). • The present study was limited by the relatively small sample size. CONCLUSIONS: • Increased mortality unrelated to PC itself was observed in men with clinically diagnosed PC, but not in screen-detected PC. • The excess mortality in men with clinically diagnosed PC seems to be as a result of a significantly increased risk of dying from neoplasm and disease of the circulatory or respiratory system. • Results have to be studied more thoroughly in further clinical trials.

Radical prostatectomy for low-risk prostate cancer following initial active surveillance: results from a prospective observational study.

BACKGROUND: Little is known about the outcome of radical prostatectomy (RP) in men initially followed on active surveillance (AS) for low-risk prostate cancer (PCa). OBJECTIVE: Evaluate pathology findings after RP in our prospective AS cohort. DESIGN, SETTING, AND PARTICIPANTS: All men participated in the Prostate Cancer Research International: Active Surveillance (PRIAS) study. Eligible men were initially diagnosed with low-risk PCa (clinical stage ≤ T2, prostate-specific antigen [PSA] ≤ 10 ng/ml, PSA density <0.2 ng/ml per ml, one or two positive biopsy cores, and Gleason score ≤ 6) and underwent RP between December 2006 and July 2011. The study protocol recommends RP in case of risk reclassification on repeat biopsy (Gleason score >6 and/or more than two positive cores) or a PSA doubling time ≤ 3 yr. MEASUREMENTS: Descriptive statistics were used to report on pathology findings for staging and grading. RESULTS AND LIMITATIONS: Pathology results were available in 167 out of 189 RP cases (88.4%). Median time to RP was 1.3 yr (range: 1.1-1.9). Protocol-based recommendations led to deferred RP in 143 men (75.7%); 24 men (12.7%) switched because of anxiety, and 22 (11.6%) had other reasons. Pathology results showed 134 (80.8%) organ-confined cases and 32 (19.2%) cases with extracapsular extension. Gleason scores ≤ 6, 3+4, 4+3, and 8 were found in 79 (47.3%), 64 (38.3%), 21 (12.6%), and 3 (1.8%) cases, respectively. Unfavourable RP results (pT3-4 and/or Gleason score ≥ 4+3) were found in 49 patients (29%), of whom 33 (67%) had a biopsy-related reason for deferred RP. CONCLUSIONS: RP results in men initially followed on AS show organ-confined disease and favourable Gleason grading in a majority of cases. Most men in our cohort had a protocol-based reason to switch to deferred RP. A main focus for AS protocols should be to improve the selection of patients at the time of inclusion to minimise reclassification of risk and preserve the chance for curative treatment, if indicated.