Prostate cancer screening in Switzerland: a literature review and consensus statement from the Swiss Society of Urology.

Over a decade ago, the United States Preventive Services Taskforce (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer in all men, which considerably influenced prostate cancer screening policies worldwide after that. Consequently, the world has seen increasing numbers of advanced stages and prostate cancer deaths, which later led the USPSTF to withdraw its initial statement. Meanwhile, the European Union has elaborated a directive to address the problem of implementing prostate cancer screening in "Europe's Beating Cancer Plan". In Switzerland, concerned urologists formed an open Swiss Prostate Cancer Screening Group to improve the early detection of prostate cancer. On the 20th of September 2023, during the annual general assembly of the Swiss Society of Urology (SGU/SSU) in Lausanne, members positively voted for a stepwise approach to evaluate the feasibility of implementing organised prostate cancer screening programs in Switzerland. The following article will summarise the events and scientific advances in the last decade during which evidence and promising additional modalities to complement PSA-based prostate cancer screening have emerged. It also aims to provide an overview of contemporary strategies and their potential harms and benefits.

Why Do Men Reject Adjuvant Radiotherapy following Radical Prostatectomy? A Systematic Survey.

INTRODUCTION: The aim of this study was to investigate non-adherence rates to adjuvant radiotherapy (aRT) after radical prostatectomy (RP) and to obtain patient reported reasons for rejecting aRT despite recommendation by a multidisciplinary team discussion (MTD). METHODS: In a retrospective monocentric analysis, we identified 1,197 prostate cancer patients who underwent RP between 2014 and 2022 at our institution, of which 735 received a postoperative MTD recommendation. Patients with a recommendation for aRT underwent a structured phone interview with predefined standardised qualitative and quantitative questions and were stratified into "adherent" (aRT performed) and "non-adherent" groups (aRT not performed). RESULTS: Of 55 patients receiving a recommendation for aRT (7.5% of all RP patients), 24 (44%) were non-adherent. Baseline tumour characteristics were comparable among the groups. "Fear of radiation damage" was the most common reason for rejection, followed by "lack of information," "feeling that the treating physician does not support the recommendation" and "the impression that aRT is not associated with improved oncological outcome." Salvage radiotherapy was performed in 25% of non-adherent patients. CONCLUSION: High rates of non-adherence to aRT after RP were observed, and reasons for this phenomenon are most likely multifactorial. Multidisciplinary and individualized patient counselling might be a key for increasing adherence rates.

Outcomes of robot-assisted laparoscopic extended pelvic lymph node dissection for prostate Cancer.

INTRODUCTION: Extended pelvic lymph node dissection (ePLND) in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) is a widely used procedure. However, little is known about anatomical site-specific yields and subsequent metastatic patterns in these patients. PATIENTS AND METHODS: Data on a consecutive series of 1107 patients undergoing RARP at our centre between 2004 and 2018 were analysed. In men undergoing LN dissection, the internal, external and obturator nodes were removed and sent in separately. We performed an analysis of LN yields in total and for each anatomical zone, patterns of LN metastases and complications. Oncological outcome in pN+ disease was assessed including postoperative PSA persistence and survival. RESULTS: A total of 823 ePLNDs were performed in the investigated cohort resulting in 98 men being diagnosed as pN+ (8.9%). The median (IQR) LN yield was 19 (14-25), 10 (7-13) on the right and 9 (6-12) on the left side (P < 0.001). A median of six (4-8) LNs were retrieved from the external, three (1-6) from the internal iliac artery, and eight (6-12) from the obturator fossa. More men had metastatic LNs on the right side compared to the left (41 vs. 19). Symptomatic lymphoceles occurred exclusively in the ePLND group (2.3% vs. 0%, p = 0.04). Postoperatively, 47 (47.9%) of men with pN+ reached a PSA of < 0.1µg/ml. There was no association between a certain pN+ region and postoperative PSA persistence or BCRFS. The estimated cancer specific survival rate at 5 years was 98.5% for pN+ disease. CONCLUSION: Robot-assisted laparoscopic ePLND with a high LN yield and low complication rate is feasible. However, we observed an imbalance in more removed and positive LNs on the right side compared to the left. A high rate of postoperative PSA persistence and early recurrence in pN+ patients might indicate a possibly limited therapeutical value of the procedure in already spread disease. Yet, these men demonstrated an excellent survival.

Is It Worth the Sweat? Prehabilitation in Uro-oncology: A Mini Review.

In several surgical specialities, exercise as part of a prehabilitation program enhances recovery. However, for uro-oncological patients, evidence up to 2020 did not demonstrate significant benefits in terms of postoperative complications or hospital length of stay (LOS). We reviewed the literature from 2020 to 2023 and screened 205 reports, of which four full texts were included. Two retrospective cohort studies, despite having potential confounding risks, indicated that preoperative exercise might reduce LOS. One of these studies also suggested a lower likelihood of complications. Present evidence hints at the potential benefits of embedding exercise in prehabilitation for uro-oncological patients, particularly for short-term functional results. However, evidence on a direct effect on postoperative complications and LOS is still inconclusive. Future research should prioritise identification of specific exercises (eg, anaerobic vs aerobic, strength training, endurance, or respiratory exercises) that yield the most cost-effective benefits. PATIENT SUMMARY: Recent studies suggest that exercising before surgery might help people with urological cancers to improve their short-term fitness. More research is needed to see if exercise before surgery shortens hospital stays or reduces complications.

Transperineal template saturation and conventional biopsy for stage prediction in prostate cancer.

OBJECTIVE: To evaluate the performance of risk calculators (RCs) predicting lymph node invasion (LNI) and extraprostatic extension (EPE) in men undergoing transperineal magnetic resonance imaging/transrectal ultrasound (TRUS)-fusion template saturation biopsy (TTSB) and conventional systematic TRUS-guided biopsy (SB). PATIENTS AND METHODS: The RCs were tested in a consecutive cohort of 645 men undergoing radical prostatectomy with extended pelvic LN dissection between 2005 and 2019. TTSB was performed in 230 (35.7%) and SB in 415 (64.3%) men. Risk of LNI and EPE was calculated using the available RCs. Discrimination, calibration, and clinical usefulness stratified by different biopsy techniques were assessed. RESULTS: Lymph node invasion was observed in 23 (10%) and EPE in 73 (31.8%) of cases with TTSB and 53 (12.8%) and 158 (38%) with SB, respectively. RCs showed an excellent discrimination and acceptable calibration for prediction of LNI based on TTSB (area under the curve [AUC]/risk estimation: Memorial Sloan Kettering Cancer Center [MSKCC]-RC 0.79/-4%, Briganti (2012)-RC 0.82/-4%, Gandaglia-RC 0.81/+6%). These were comparable in SB (MSKCC-RC 0.78/+2%; Briganti (2012)-RC 0.77/-3%). Decision curve analysis (DCA) revealed a net benefit at threshold probabilities between 3% and 6% when TTSB was used. For prediction of EPE based on TTSB an inferior discrimination and variable calibration were observed (AUC/risk estimation: MSKCC-RC 0.71/+8% and Martini (2018)-RC 0.69/+2%) achieving a net benefit on DCA only at risk thresholds of >17%. Performance of RCs for prediction of LNI and EPE based on SB showed comparable results with a better performance in the DCA for LNI (risk thresholds 1-2%) and poorer performance for EPE (risk threshold >20%). This study is limited by its retrospective single-institution design. CONCLUSIONS: The potentially more accurate grading ability of TTSB did not result in improved performance of preoperative RCs. Prediction tools for LNI proved clinical usefulness while RCs for EPE did not.

The role of primary retroperitoneal lymph node dissection in the treatment of stage II seminoma.

PURPOSE OF REVIEW: Stage II seminoma is responsive to chemo- or radiotherapy with a progression-free survival of 87-95% at 5 years but at the cost of short- and long-term toxicity. After evidence about these long-term morbidities emerged, four surgical cohorts investigating the role of retroperitoneal lymph node dissection (RPLND) as a treatment option for stage II disease were initiated. RECENT FINDINGS: Currently, two RPLND series have been published as a complete report, while data from other series have only been published as congress abstracts. In series without adjuvant chemotherapy, recurrence rates ranged from 13% to 30% after follow-ups of 21-32 months. In those receiving RPLND and adjuvant chemotherapy, the recurrence rate was 6% after a mean follow-up of 51 months. Across all trials, recurrent disease was treated with systemic chemotherapy (22/25), surgery (2/25), and radiotherapy (1/25). The rate of pN0 disease after RPLND varied between 4% and 19%. Postoperative complications were reported in 2-12%, while antegrade ejaculation was maintained in 88-95% of patients. Median length of stay ranged from 1 to 6 days. SUMMARY: In men with clinical stage II seminoma, RPLND is a safe and promising treatment option. Further research is needed to determine the risk of relapse and to personalize treatment options based on patient-specific risk factors.

Therapy decisions after diagnosis of prostate cancer in men with negative prostate MRI.

BACKGROUND: To investigate the clinical implications of magnetic resonance imaging (MRI) negative prostate cancer (PCa) in a cohort of men undergoing transperineal prostate biopsy. METHODS: We included all men without prior diagnosis of PCa undergoing transperineal template saturation ± fusion-guided targeted biopsy of the prostate between November 2014 and March 2018. Before biopsy, all patients underwent MRI and biopsies were performed irrespective of imaging results. Baseline characteristics, imaging, biopsy results, and follow-up information were retrieved from the patient charts. Patients were classified as either MRI negative (Prostate Imaging Reporting and Data System [PIRADS] ≤ 2) or positive (PIRADS ≥ 3). ISUP grade group 1 was defined as clinically nonsignificant (nsPCa) and ≥2 as clinically significant PCa (csPCa). Primary outcome was the individual therapeutic decision after diagnosis of PCa stratified according to MRI visibility. Secondary outcomes were the sensitivity and specificity of MRI, and the urooncological outcomes after radical prostatectomy (RP). RESULTS: From 515 patients undergoing prostate biopsy, 171 (33.2%) patients had a negative and 344 (66.8%) a positive MRI. Pathology review stratified for MRI negative and positive cases revealed nsPCa in 27 (15.8%) and 32 (9.3%) and csPCa in 26 (15.2%) and 194 (56.4%) of the patients, respectively. The rate of active treatment in the MRI negative was lower compared with the MRI positive cohort (12.3% vs. 53.2%; odd ratio [OR] = 0.12; p < 0.001). While men with negative MRI were more likely to undergo active surveillance (AS) than MRI positive patients (18.1% vs. 10.8%; OR = 1.84; p = 0.027), they rarely underwent RP (6.4% vs. 40.7%, OR = 0.10; p < 0.001). Logistic regression revealed that a negative MRI was independently protective for active treatment (OR = 0.32, p = 0.014). The specificity, sensitivity, negative, and positive predictive value of MRI for detection of csPCa were 49.2%, 88.2%, 56.4%, and 84.8%, respectively. The rate of adverse clinicopathological outcome features (pT3/4, ISUP ≥4, or prostate-specific antigen [PSA]-persistence) following RP was 4.7% for men with MRI negative compared to 17.4% for men with MRI positive PCa (OR = 3.1, p = 0.19). CONCLUSION: Only few men with MRI negative PCa need active cancer treatment at the time of diagnosis, while the majority opts for AS. Omitting prostate biopsies and performing a follow-up MRI may be a safe alternative to reduce the number of unnecessary interventions.

Prospective observational study of the role of the microbiome in BCG responsiveness prediction (SILENT-EMPIRE): a study protocol.

INTRODUCTION: The human microbiota, the community of micro-organisms in different cavities, has been increasingly linked with inflammatory and neoplastic diseases. While investigation into the gut microbiome has been robust, the urinary microbiome has only recently been described. Investigation into the relationship between bladder cancer (BC) and the bladder and the intestinal microbiome may elucidate a pathophysiological relationship between the two. The bladder or the intestinal microbiome or the interplay between both may also act as a non-invasive biomarker for tumour behaviour. While these associations have not yet been fully investigated, urologists have been manipulating the bladder microbiome for treatment of BC for more than 40 years, treating high grade non-muscle invasive BC (NMIBC) with intravesical BCG immunotherapy. Neither the association between the microbiome sampled directly from bladder tissue and the response to BCG-therapy nor the association between response to BCG-therapy with the faecal microbiome has been studied until now. A prognostic tool prior to initiation of BCG-therapy is still needed. METHODS AND ANALYSIS: In patients with NMIBC bladder samples will be collected during surgery (bladder microbiome assessment), faecal samples (microbiome assessment), instrumented urine and blood samples (biobank) will also be taken. We will analyse the microbial community by 16S rDNA gene amplicon sequencing. The difference in alpha diversity (diversity of species within each sample) and beta diversity (change in species diversity) between BCG-candidates will be assessed. Subgroup analysis will be performed which will lead to the development of a clinical prediction model estimating risk of BCG-response. ETHICS AND DISSEMINATION: The study has been approved by the Cantonal Ethics Committee Zurich (2021-01783) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences. TRIAL REGISTRATION NUMBER: NCT05204199.