Long term experience of robotic retroperitoneal partial nephrectomy as the default approach in the management of renal masses: should the paradigm shift?

Although retroperitoneal surgery has demonstrated a better quality of recovery compared to transperitoneal routes, Retroperitoneal Robot Assisted Partial Nephrectomy (RRAPN) remains proportionally infrequent. As the boundaries of what is achievable robotically continue to be pushed, we present our experience at a high-volume tertiary referral centre that specialises in retroperitoneal surgery, exploring its feasibility as standard of care in the management of small renal masses. A prospective database of 784 RAPNs (2009-2020) was reviewed and 721 RRAPNs (92%) were performed at our centre. In our practice, we utilise a four-port approach to RRAPN. Patient, tumour and operative characteristics were assessed and both oncological outcomes and trifecta and pentafecta achievements were determined. Pentafecta was defined as achieving trifecta (negative surgical margin, no post-operative complications and WIT of < 25 min) plus over 90% estimated GFR preservation and no CKD stage upgrading at 1 year. Multivariate analysis was conducted to predict peri-operative factors which may prevent achieving a trifecta/pentafecta outcome. From 784 cases, 112 RAPNs were performed for imperative reasons, whilst the remainder were elective. Mean BMI ± s.d amongst our cohort was 28.6 ± 5.7. Mean tumour size was 3.1 cm (range 0.8-10.5 cm) and 47% of cases were stratified as intermediate/high risk using R.E.N.A.L nephrometry scoring. Forty-six patients had lesions in a hilar location, and 31% were anterior. Median blood loss was 30mls, with an open conversion rate of 1% and transfusion rate of 1.6%. Median warm ischaemic time (WIT) was 21 min, positive surgical margins were found in 4% and our post-operative Clavien 3/ > complication rate was 2.6%. We had a 1-day median length of stay with a 30 day readmission rate of 2%. Of 631 patients (80%) with a definitive histological diagnosis of cancer, 23% had T1b/ > disease. Over a mean 15 month follow-up period (range 1-125 months), 2% of patients developed recurrences and our cohort demonstrated a 99% 5 year cancer specific survival. Trifecta was achieved in 67% of cases and pentafecta in 47%. Age (p = 0.05), operative time (p = 0.008), pT1b tumours (p = 0.03), R.E.N.A.L score and blood loss (p = 0.001) were found to statistically significantly influence achievement of trifecta. Pentafecta achievement was influenced by R.E.N.A.L score (p = 0.008), operative time (p = 0.001) and blood loss (p = 0.001). We demonstrate the retroperitoneal approach in RAPN is feasible and safe irrespective of lesion location and complexity. In the hands of high-volume centres that are skilled in the retroperitoneal approach the benefits of retroperitoneal surgery can be extended even to challenging cohorts of patients without compromising their oncological or functional outcomes.

Melanosis of the urinary bladder.

Melanosis bladder refers to the urothelium of the bladder appearing black and velvety, with microscopic evaluation describing melanin deposition. Risk factors, pathogenesis and clinical implications are unknown because only sporadic cases are reported in the literature, both with and without the presence of urinary tract symptoms or malignancy. We report a case of melanosis bladder in a male patient with voiding urinary symptoms and an untreated hypospadias.

Genetics of prostate cancer and its utility in treatment and screening.

Prostate cancer heritability is attributed to a combination of rare, moderate to highly penetrant genetic variants as well as commonly occurring variants conferring modest risks [single nucleotide polymorphisms (SNPs)]. Some of the former type of variants (e.g., BRCA2 mutations) predispose particularly to aggressive prostate cancer and confer poorer prognoses compared to men who do not carry mutations. Molecularly targeted treatments such as PARP inhibitors have improved outcomes in men carrying somatic and/or germline DNA repair gene mutations. Ongoing clinical trials are exploring other molecular targeted approaches based on prostate cancer somatic alterations. Genome wide association studies have identified >250 loci that associate with prostate cancer risk. Multi-ancestry analyses have identified shared as well as population specific risk SNPs. Prostate cancer risk SNPs can be used to estimate a polygenic risk score (PRS) to determine an individual's genetic risk of prostate cancer. The odds ratio of prostate cancer development in men whose PRS lies in the top 1% of the risk profile ranges from 9 to 11. Ongoing studies are investigating the utility of a prostate cancer PRS to target population screening to those at highest risk. With the advent of personalized medicine and development of DNA sequencing technologies, access to clinical genetic testing is increasing, and oncology guidelines from bodies such as NCCN and ESMO have been updated to provide criteria for germline testing of "at risk" healthy men as well as those with prostate cancer. Both germline and somatic prostate cancer research have significantly evolved in the past decade and will lead to further development of precision medicine approaches to prostate cancer treatment as well as potentially developing precision population screening models.