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Abstract Introduction A prospective cohort study comparing peri‐ and postoperative outcomes for patients with predominantly anterior prostate cancer (APC) identified preoperatively against non‐anterior prostate cancer (NAPC) treated via robotic‐assisted radical prostatectomy (RARP). Patients and Methods Of the 757 RARP's completed between January 2016 and April 2018, two comparative cohorts for anterior and an equivalent group of non‐anterior prostate tumours each consisting of 152 patients were compared against each other. Data were collected on the following variables: patient age; operating consultant; preoperative PSA, ISUP grade, degree of nerve sparing; tumour staging; presence and location of positive surgical margins; PSA density, postoperative ISUP grade; treatment paradigm and postoperative PSA, erectile function, and continence outcomes with 2‐year follow‐up. Results APCs were found to have significantly lower ISUP grading postoperatively; increased diagnosis via active surveillance over new diagnosis; more frequently undertaken bilateral nerve‐sparing and long‐term poorer continence outcomes at 18 and 24 months postoperatively (p 0.05). Conclusion The lower ISUP grading could indicate APC as overall being less aggressive than NAPC, whereas the poorer long‐term continence outcomes require further investigating. The non‐significant differences amongst tumour staging, PSA density, preoperative PSA levels and PSM rates suggest that APC may not be as significant as predicted in diagnostic evaluation. Overall, this study provides useful information on the growing literature of anterior prostate cancer. Being the largest comparative cohort study to date on APC post‐RARP, these results indicate the true characteristics of anterior tumours and their functional outcomes to help improve education, patient expectations and management.

Abstract Objective To report on the outcomes of urological cancer patients undergoing radical surgery between March–September 2020 (compared with 2019) in the European Institute of Oncology (IEO) in Milan and the South East London Cancer Alliance (SELCA). Materials and Methods Since March 2020, both institutions implemented a COVID‐19 minimal ‘green’ pathway, whereby patients were required to isolate for 14 days prior to admission and report a negative COVID‐19 polymerase chain reaction (PCR) test within 3 days of surgery. COVID‐19 positive patients had surgery deferred until a negative swab. Surgical outcomes assessed were: American Society of Anaesthesiologists (ASA) grade; surgery time; theatre time; intensive care unit (ICU) stay >24 h; pneumonia; length of stay (LOS); re‐admission. Postoperative COVID‐19 infection rates and associated mortality were also recorded. Results At IEO, uro‐oncological surgery increased by 4%, as compared with the same period in 2019 (n = 515 vs. 534). The main increase was observed for renal (16%, n = 98 vs. 114), bladder (24%, n = 45 vs. 56) and testicular (27%, n = 26 vs. 33). Patient demographics were all comparable between 2019 and 2020. Only one bladder cancer patient developed COVID‐19, reporting mild/moderate disease. There was no COVID‐19 associated mortality. In the SELCA cohort, uro‐oncological surgery declined by 23% (n = 403 vs. 312) compared with the previous year. The biggest decrease was seen for prostate (−42%, n = 156 vs. 91), penile (−100%, n = 4 vs. 0) and testicular cancers (−46%, n = 35 vs. 24). Various patient demographic characteristics were notably different when comparing 2020 versus 2019. This likely reflects the clinical decision of deferring COVID‐19 vulnerable patients. One patient developed COVID‐19, with no COVID‐19 related mortality. Conclusion The COVID‐19 minimal ‘green’ pathways that were put in place have shown to be safe for uro‐oncological patients requiring radical surgery. There were limited complications, almost no peri‐operative COVID‐19 infection and no COVID‐19‐related mortality in either cohort.

Purpose There is debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation in addition to prostate bed radiotherapy when used to treat disease recurrence following radical prostatectomy. We compared toxicity from radiation therapy (RT) to the prostate bed and pelvic lymph nodes (PBPLN-RT) with prostatebed only radiation therapy (PBO-RT) following radical prostatectomy. Methods and Materials Patients with prostate cancer who underwent post-prostatectomy RT between 2010 and 2016 were identified by using the National Prostate Cancer Audit (NPCA) database. Follow-up data was available up to December 31, 2018. Validated outcome measures, based on a framework of procedural and diagnostic codes, were used to capture ≥Grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity. An adjusted competing-risks regression analysis estimated subdistribution hazard ratios (sHR). A sHR > 1 indicated a higher incidence of toxicity with PBPLN-RT than with PBO-RT. Results 5-year cumulative incidences in the PBO-RT (n = 5,087) and PBPLNRT (n = 593) groups was 18.2% and 15.9% for GI toxicity, respectively. For GU toxicity it was 19.1% and 20.7%, respectively. There was no evidence of difference in GI or GU toxicity after adjustment between PBO-RT and PBPLN-RT (GI: adjusted sHR, 0.90, 95% CI, 0.67–1.19; P = 0.45); (GU: adjusted sHR, 1.19, 95% CI, 0.99–1.44; P = 0.09). Conclusions This national population-based study found that including PLNs in the radiation field following radical prostatectomy is not associated with a significant increase in rates of ≥Grade 2 GI or GU toxicity at 5 years.

Abstract Objectives To determine the safety of urological admissions and procedures during the height of the COVID‐19 pandemic using “hot” and “cold” sites. The secondary objective is to determine risk factors of contracting COVID‐19 within our cohort. Patients and methods A retrospective cohort study of all consecutive patients admitted from March 1 to May 31, 2020 at a high‐volume tertiary urology department in London, United Kingdom. Elective surgery was carried out at a “cold” site requiring a negative COVID‐19 swab 72‐hours prior to admission and patients were required to self‐isolate for 14‐days preoperatively, while all acute admissions were admitted to the “hot” site. Complications related to COVID‐19 were presented as percentages. Risk factors for developing COVID‐19 infection were determined using multivariate logistic regression analysis. Results A total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44‐70) were admitted under the urology team; 101 (16.5%) on the “cold” site and 510 (83.5%) on the “hot” site. Procedures were performed in 495 patients of which eight (1.6%) contracted COVID‐19 postoperatively with one (0.2%) postoperative mortality due to COVID‐19. Overall, COVID‐19 was detected in 20 (3.3%) patients with two (0.3%) deaths. Length of stay was associated with contracting COVID‐19 in our cohort (OR 1.25, 95% CI 1.13‐1.39). Conclusions Continuation of urological procedures using “hot” and “cold” sites throughout the COVID‐19 pandemic was safe practice, although the risk of COVID‐19 remained and is underlined by a postoperative mortality.

Abstract Background Metformin is a biguanide oral hypoglycaemic agent commonly used for the treatment of type 2 diabetes mellitus. In addition to its anti-diabetic effect, metformin has also been associated with a reduced risk of cancer incidence of a number of solid tumours, including prostate cancer (PCa). However, the underlying biological mechanisms for these observations have not been fully characterised in PCa. One hypothesis is that the indirect insulin lowering effect may have an anti-neoplastic action as elevated insulin and insulin like growth factor − 1 (IGF-1) levels play a role in PCa development and progression. In addition, metformin is a potent activator of activated protein kinase (AMPK) which in turn inhibits the mammalian target of rapamycin (mTOR) and other signal transduction mechanisms. These direct effects can lead to reduced cell proliferation. Given its wide availability and tolerable side effect profile, metformin represents an attractive potential therapeutic option for men with PCa. Hence, the need for a clinical trial investigating its biological mechanisms in PCa. Methods METAL is a randomised, placebo-controlled, double-blind, window of opportunity study investigating the biological mechanism of metformin in PCa. 100 patients with newly-diagnosed, localised PCa scheduled for radical prostatectomy will be randomised 1:1 to receive metformin (1 g b.d.) or placebo for four weeks (+/− 1 week) prior to prostatectomy. Tissue will be collected from both diagnostic biopsy and prostatectomy specimens. The primary endpoint is the difference in expression levels of markers of the Fatty acid synthase (FASN)/AMPK pathway pre and post treatment between the placebo and metformin arms. Secondary endpoints include the difference in expression levels of indicators of proliferation (ki67 and TUNEL) pre and post treatment between the placebo and metformin arms. METAL is currently open to recruitment at Guy’s and St Thomas’ Hospital and the Royal Marsden Hospital, London. Discussion This randomised placebo-controlled double blinded trial of metformin vs. placebo in men with localised PCa due to undergo radical prostatectomy, aims to elucidate the mechanism of action of metformin in PCa cells, which should then enable further larger stratification trials to take place. Trial registration EudraCT number 2014–005193-11 . Registered on September 09, 2015.

Isolation of circulating tumor cells (CTCs) from peripheral blood has the potential to provide a far easier "liquid biopsy" than tumor tissue biopsies, to monitor tumor cell populations during disease progression and in response to therapies. Many CTC isolation technologies have been developed. We optimized the Parsortix system, an epitope independent, size and compressibility-based platform for CTCs isolation, making it possible to harvest CTCs at the speed and sample volume comparable to standard CellSearch system. We captured more than half of cancer cells from different cancer cell lines spiked in blood samples from healthy donors using this system. Cell loss during immunostaining of cells transferred and fixed on the slides is a major problem for analyzing rare cell samples. We developed a novel cell transfer and fixation method to retain >90% of cells on the slide after the immunofluorescence process without affecting signal strength and specificity. Using this optimized method, we evaluated the Parsortix system for CTC harvest in prostate cancer patients in comparison to immunobead based CTC isolation systems IsoFlux and CellSearch. We harvested a similar number (p = 0.33) of cytokeratin (CK) positive CTCs using Parsortix and IsoFlux from 7.5 mL blood samples of 10 prostate cancer patients (an average of 33.8 and 37.6 respectively). The purity of the CTCs harvested by Parsortix at 3.1% was significantly higher than IsoFlux at 1.0% (p = 0.02). Parsortix harvested significantly more CK positive CTCs than CellSearch (p = 0.04) in seven prostate cancer patient samples, where both systems were utilized (an average of 32.1 and 10.1 respectively). We also captured CTC clusters using Parsortix. Using four-color immunofluorescence we found that 85.8% of PC3 cells expressed EpCAM, 91.7% expressed CK and 2.5% cells lacked both epithelial markers. Interestingly, 95.6% of PC3 cells expressed Vimentin, including those cells that lacked both epithelial marker expression, indicating epithelial-to-mesenchymal transition. CK-positive/Vimentin-positive/CD45-negative, and CK-negative/Vimentin-positive/CD45-negative cells were also observed in four of five prostate cancer patients but rarely in three healthy controls, indicating that Parsortix harvests CTCs with both epithelial and mesenchymal features. We also demonstrated using PC3 and DU145 spiking experiment that Parsortix harvested cells were viable for cell culture.