SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. METHODS: 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. DISCUSSION: This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. TRIAL REGISTRATION: This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Association between Hidradenitis Suppurativa and Abnormalities in Semen Parameters and Sexual Function: A Pilot Study.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting patients of reproductive age. Although HS shares risk factors with male infertility, only 1 epidemiological study has evaluated this association. To further evaluate this potential association, findings on semen and hormonal analysis, testicular ultrasound, and the International Index of Erectile Function (IIEF-15) were compared between 28 men attending a tertiary HS clinic during the period April 2019 to April 2021, and 44 healthy controls, spouses of infertile women undergoing semen evaluation before in vitro fertilization. Patients with HS were divided based on the absence or presence of gluteal and genital lesions. Patients with HS were younger than controls (median 27 vs 34 years, p < 0.0004) and had a higher proportion of smokers (86% vs 33%, p < 0.0001). Semen parameters in patients with gluteal-genital lesions, specifically those with severe scrotal involvement necessitating surgery, were lower than the WHO reference values and significantly lower than in patients without gluteal-genital lesions and controls. Erectile dysfunction was reported by 93% of patients with HS. These findings suggest that spermatogenesis and sexual function may be impaired in young men with HS. Therefore, multidisciplinary management of HS should include their evaluation to identify patients who might benefit from semen cryopreservation and sexual treatment.

Association between early change in neutrophil-to-lymphocyte ratio after radical cystectomy and treatment outcomes.

OBJECTIVES: To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy. PATIENTS AND METHODS: We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival. RESULTS: The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P < 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004). CONCLUSIONS: Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Fascial dehiscence after radical cystectomy: Is abdominal exploration mandatory?

BACKGROUND: Fascial dehiscence after radical cystectomy may have serious clinical implications. To optimize its management, we sought to describe accompanying intraabdominal findings of post-cystectomy dehiscence repair and determine whether a thorough intraabdominal exploration during its operation is mandatory. METHODS: We retrospectively reviewed a multi-institutional cohort of patients who underwent open radical cystectomy between 2005 and 2020. Patients who underwent exploratory surgery due to fascial dehiscence within 30 days post-cystectomy were included in the analysis. Data collected included demographic characteristics, the clinical presentation of dehiscence, associated laboratory findings, imaging results, surgical parameters, operative findings, and clinical implications. Potential predictors of accompanying intraabdominal complications were investigated. RESULTS: Of 1301 consecutive patients that underwent cystectomy, 27 (2%) had dehiscence repair during a median of 7 days post-surgery. Seven patients (26%) had accompanying intraabdominal pathologies, including urine leaks, a fecal leak, and an internal hernia in 5 (19%), 1 (4%), and 1 (4%) patients, respectively. Accompanying intraabdominal findings were associated with longer hospital stay [20 (IQR 17, 23) vs. 41 (IQR 29, 47) days, P = 0.03] and later dehiscence identification (postoperative day 7 [IQR 5, 9] vs. 10 [IQR 6, 15], P = 0.03). However, the rate of post-exploration complications was similar in both groups. A history of ischemic heart disease was the only predictor for accompanying intraabdominal pathologies (67% vs. 24%; P = 0.02). CONCLUSIONS: A substantial proportion of patients undergoing post-cystectomy fascial dehiscence repair may have unrecognized accompanying surgical complications without prior clinical suspicion. While cardiovascular disease is a risk factor for accompanying findings, meticulous abdominal inspection is imperative in all patients during dehiscence repair. Identification and repair during the surgical intervention may prevent further adverse, possibly life-threatening consequences with minimal risk for iatrogenic injury.

Trends in urological emergencies in the Era of COVID-19.

PURPOSE: To evaluate trends in emergency room (ER) urological conditions during COVID-19 pandemic lockdown. MATERIALS AND METHODS: Retrospective analyses of renal colic, hematuria, and urinary retention in ER's admissions of a tertiary hospital during the lockdown period (March 19 to May 4, 2020) in Israel. Patient's demographics and clinical characteristics were compared to those in corresponding periods during 2017-2019, with estimated changes in ER arrival and waiting times, utilization of imaging tests, numbers of hospitalizations, and urgent procedure rates. RESULTS: The number of ER visits for renal colic, hematuria, and urinary retention decreased by 37%, from an average of 451 (2017-2019) to 261 patients (2020). Clinical severity was similar between groups, with no major differences in patient's age, vital signs, or laboratory results. The proportion of ER visits during night hours increased significantly during lockdown (44.8% vs. 34.2%, p=0.002). There was a decrease in renal colic admission rate from 19.8% to 8.4% (p=0.001) without differences in urgent procedures rates, while the 30-day revisit rate decreased from 15.8% to 10.3% during lockdown (p=0.02). CONCLUSIONS: General lockdown was accompanied by a significant decrease in common urological presentations to the ER. This change occurred across the clinical severity spectrum of renal colic, hematuria, and urinary retention. In the short term, it appears that patients who sought treatment did not suffer from complications that could be attributed to late arrival or delay in treatment. The long-term implications of abstinence from seeking emergent care are not known and require further investigation.

[BLADDER PAIN SYNDROME - DOES DETRUSOR MASTOCYTOSIS PREDICT SYMPTOMATIC IMPROVEMENT FOLLOWING BLADDER HYDRODISTENTION UNDER ANESTHESIA?]

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, debilitating syndrome involving bladder pain and lower urinary tract symptoms (LUTS), with a substantial effect on patients' quality of life. IC/BPS poses a diagnostic challenge, and its available treatment options remain only moderately effective. Bladder-wall biopsies from IC/BPS patients commonly uncover mastocytosis. While mast-cells are suspected as pivotal in disease pathogenesis, the clinical significance of their presence remains unclear. Clinical guidelines differ on whether or not bladder biopsies should be a part of routine IC/BPS workup. AIMS: To determine whether detrusor mastocytosis can serve as a prognostic marker for treatment response and improvement duration. METHODS: We retrospectively collected patient data for IC/BPS patients who underwent bladder hydrodistension under anesthesia. We used statistical modelling to determine the effect of mastocystosis and other possible predictive factors - age, comorbidity, Hunner lesions - on the presence and duration of symptom improvement. RESULTS: A total of 35 patients (89% female, median age 63.5 [IQR 48.8-73.6] years) underwent hydrodistension, of whom 28 (89% female, median age 63.0 [44.8-73.1] years) had bladder biopsies; 11 (39%) of them had mastocystosis. Within a median follow-up of 8.8 [1.7-24.2] months, 11 (100%) of the patients with mastocytosis and 9 (53%) of the patients without it, experienced symptomatic improvement (p=0.007). Improvement duration was 8 months longer (p=0.006) in those with mastocystosis. Univariate logistic regression models were used to estimate odds ratios (OR). Mastocytosis (p=0.004) and Charlson Comorbidity score were the only variables with a statistically significant OR. Univariate survival models were fitted, and improvement duration was estimated to be longer in patients with mastocystosis (p=0.01). A multivariate Cox regression model found no variable to be statistically significant, though mastocystosis was borderline significant (p=0.055). CONCLUSIONS: Mastocystosis defines a discernible phenotype of IC/BPS, which exhibits higher rates and longer duration of hydrodistention treatment response. DISCUSSION: Notwithstanding limitations of sample size and retrospective study design, we were able to demonstrate that mastocystosis can serve as a prognostic factor for symptom improvement after hydrodistension in IC/BPS patients. Prospective studies are required to validate this finding and to investigate the mechanisms involved.

Short-Term Outcomes of Active Surveillance for Low Risk Prostate Cancer among Men with Germline DNA Repair Gene Mutations.

PURPOSE: Men with germline mutations in DNA repair genes have a higher risk of prostate cancer. Active surveillance is the preferred treatment modality for low risk prostate cancer. However, many fear offering this alternative to men with germline mutations. We describe the short-term oncologic outcomes of active surveillance in a population of men with a high genetic predisposition for prostate cancer. MATERIALS AND METHODS: A prospective cohort of men with germline DNA repair gene mutations were diagnosed with Grade Group 1 prostate cancer. All men were offered active surveillance. Followup consisted of prostate specific antigen every 3 months, multiparametric magnetic resonance imaging and a magnetic resonance imaging-ultrasound fusion confirmatory biopsy within 1 year of diagnosis. The primary end points included treatment and progression-free survival. RESULTS: Eighteen carriers of DNA repair gene mutations were diagnosed with low risk prostate cancer (BRCA1 [8], BRCA2 [6], CHEK2 [2], Lynch syndrome [2]). Of these patients 15 (83%) initiated active surveillance and 3 (17%) declined. All but 1 were fully compliant with the active surveillance protocol (93%). Overall 20% (3) had upgrading at confirmatory biopsy and were treated. At a median followup of 28 months (IQR 8.5-42) 80% of patients (12) on active surveillance are free from upgrading or radical treatment. CONCLUSIONS: Active surveillance may be feasible among carriers diagnosed with low risk prostate cancer. If embarking on active surveillance, carriers should be very carefully monitored at a specialized clinic, optimizing patient compliance and minimizing risk. Until larger scale studies with long-term followup become available, this option should be cautiously discussed with the patient.

Catheter-associated meatal pressure injury in hospitalized males.

AIMS: To assess the prevalence of catheter-associated meatal pressure injury in acute hospitalized males, to determine risk factors for its formation and to propose a grading system for meatal pressure injury severity. METHODS: In this cross-sectional study, we screened all adult males concurrently hospitalized at a tertiary medical center for indwelling urethral catheters and for meatal pressure injury. We proposed a system to grade meatal pressure injury severity and used logistic-regression modeling to calculate odds ratios (ORs) of possible risk factors. RESULTS: A number of 168/751 (22.4%) hospitalized males with indwelling urethral catheters were included. Median age was 70.5 (inter-quartile range [IQR]: 57.0-80.3) years, median time from catheterization 5.5 (IQR: 2-11) days. A total of 61 (36%) had meatal pressure injury, as early as the first day after catheterization. Grade III injuries (<2 cm ulcer) developed in 22 (13%) patients, earliest noted on the second catheter day, and grade IV injuries (≥2 cm) in 7 (4%) patients, as early as 5 days post catheterization. In a multivariable analysis, catheter fixation (OR: 0.26 [95% CI: 0.10-0.70]; P = .008) was associated with reduced risk of meatal pressure injury, while catheter presence over 14 days (OR: 1.46 [95% CI: 1.01-1.08]; P = .005) and other skin ulcers (OR: 2.45 [95% CI: 1.05-5.71]; P = .038) were associated with a higher risk of meatal pressure injury. CONCLUSIONS: Meatal pressure injury is a common complication of indwelling catheters in hospitalized males, beginning days after catheterization. Meatal pressure injury was associated with prolonged catheter presence, other pressure injuries, and lack of catheter fixation. Prospective studies are needed to establish evidence-based guidelines.

Fistulous Complications following Radical Cystectomy for Bladder Cancer: Analysis of a Large Modern Cohort.

PURPOSE: Fistula formation is a rare and poorly described complication following radical cystectomy with urinary diversion. We sought to identify patients who experienced any type of fistulous complication and we analyzed risk factors for formation as well as management outcomes. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent radical cystectomy for bladder cancer at our institution. Patients who experienced any fistula were identified. Risk factors, management strategies and outcomes were analyzed. Patients underwent initial conservative treatment and those in whom this treatment failed underwent surgical repair. Univariable and multivariable analyses were performed to identify predictors of fistula formation as well as the need for surgical repair. RESULTS: Of the 1,041 patients 31 (3.0%) experienced fistula formation. Median time to fistula presentation was 31 days. Enterodiversion was the most common fistula type, noted in 54.8% of patients, followed by enterocutaneous and diversion cutaneous treatment in 29.0% and 12.9%, respectively. On multivariable analyses a history of radiation therapy (OR 3.1, p = 0.03) and an orthotopic neobladder (OR 3.1, p = 0.04) were predictors of fistula formation. Conservative management was successful in 41.9% of cases. There were no predictors of failed conservative management. Of patients who required surgical repair success was achieved in 94.4% at a single operation. CONCLUSIONS: Fistulas are rare after radical cystectomy and they are most common between the urinary diversion and the small bowel. A history of radiation therapy and a orthotopic neobladder are risk factors for formation. When required, surgical repair is generally successful at a single operation.

Dynamic 11C-Choline PET / CT for the primary diagnosis of prostate cancer.

OBJECTIVES: To test the ability of dynamic 11C-PET / CT to discriminate cancerous tissue from background tissue in patients with localized prostate cancer. MATERIALS AND METHODS: Twenty-four consecutive patients with prostate cancer were prospectively evaluated with dynamic 11C-choline PET / CT prior to radical prostatectomy. The PET / CT scan was divided into 18 sequences of 5 seconds each, followed by 9 sequences of 60 seconds each. Whole-mount sections of harvested prostates served as reference standards. Volumes of interest were positioned on the dynamic PET / CT images and the following quantitative variables were calculated: perfusion coefficient (K1), washout constant (K2), area under the curve (AUC) at 175 and 630 seconds, and average and maximum standardized uptake values (SUVavg, and SUVmax). Wilcoxon signed-ranks test was used to compare benign and cancerous areas of the prostate. RESULTS: Areas of cancerous tissue were characterized by higher SUVavg and SUVmax than areas of benign tissue (3.67 ± 2.7 vs. 2.08 ± 1.3 and 5.91 ± 4.4 vs. 3.71 ± 3.7, respectively, P < 0.001), in addition to a higher K1 (0.95 ± 0.58 vs. 0.43 ± 0.24, P < 0.001) and greater cumulative tracer uptake, represented by the AUC at 175 and 630 seconds (P <0.001). No associations were found between dynamic parameters and preoperative prostate specific antigen level or Gleason score. CONCLUSIONS: In this pilot study, 11C-choline PET / CT demonstrated increased tracer uptake with higher values of static and dynamic parameters in areas of prostate cancer compared to areas of benign tissue. Larger studies are warranted to validate these results and examine the potential applicability of 11C-choline dynamic PET / CT for the diagnosis of prostate cancer.

The testis-specific USP26 is a deubiquitinating enzyme of the ubiquitin ligase Mdm2.

Murine double minute-2 (Mdm2) is one of the E3-ligases of the androgen receptor besides being the major regulator of the p53 tumor suppressor. The testis-specific USP26 was demonstrated to regulate the androgen receptor. In the present study we examined possible association between the deubiquitinating enzyme - ubiquitin specific protease 26 (USP26), and the oncoprotein E3 ligase - (Mdm-2). We analyzed the half-life time of USP26 in HEK293 cells. In a cell-free system we asked whether USP26 can be ubiquitinated by HeLa extract. In co-transfection experiments we expressed Mdm2 along with different constructs of USP26 in order to examine possible regulation of Mdm2 by USP26. We found that USP26 binds to Mdm2 through its coiled-coiled C-terminal domain. USP26 deubiquitinates Mdm2 and stabilizes it. The physiological significance of the findings is still not fully understood. The interaction between USP26 and Mdm2, and the subsequent deubiquitination of Mdm2, serves, most probably to regulate Mdm2. Future therapeutic modalities that interfere with the association between USP26 and Mdm2 will be used to destabilize the ligase in malignancies where it is upregulated.

Safety and early effectiveness of robot-assisted partial nephrectomy for large angiomyolipomas.

OBJECTIVE: To evaluate a multicentre series of robot-assisted partial nephrectomy (RAPN) performed for the treatment of large angiomyolipomas (AMLs). PATIENTS AND METHODS: Between 2005 and 2016, 40 patients with large or symptomatic AMLs underwent RAPN at five academic centres in the USA. Patient demographics, AML characteristics, operative and postoperative clinical outcomes were recorded and analysed. Surgical outcomes were compared between patients who underwent selective arterial embolisation (SAE) before RAPN and patients who did not undergo pre-RAPN SAE. RESULTS: The median (interquartile range [IQR]) tumour diameter was 7.2 (5-8.5) cm, and the median (IQR) nephrometry score was 9 (7-10). Six patients (15%) had a history of tuberous sclerosis and 11 (28%) had previously undergone SAE. The median (IQR) operative time and warm ischaemia time was 207 (180-231) and 22.5 (16-28) min, respectively. A non-clamping technique was used in eight (20%) patients. The median (IQR) estimated blood loss was 200 (100-245) mL, and four patients (10%) received blood transfusion postoperatively. One intraoperative complication occurred (2.5%), and seven postoperative complications occurred in six patients (15%). During a median (IQR) follow-up of 8 (1-15) months, none of the patients developed AML-related symptoms. The median estimated glomerular filtration rate preservation rate was 95%. There were no differences in operative or perioperative outcomes between patients who underwent SAE before RAPN and those who did not. CONCLUSIONS: Robot-assisted partial nephrectomy appears to be a safe primary or secondary (post-SAE) treatment for large AMLs, with a favourable perioperative morbidity profile and excellent functional preservation. Longer follow-up is required to fully evaluate therapeutic efficacy.

Prediction of renal mass aggressiveness using clinical and radiographic features: a global, multicentre prospective study.

OBJECTIVE: To examine the ability of preoperative clinical characteristics to predict histological features of renal masses (RMs). PATIENTS AND METHODS: Data from consecutive patients with clinical stage I RMs treated surgically between 2010 and 2011 in the Clinical Research Office of Endourology Society (CROES) Renal Mass Registry were collected. Based on surgical histology, tumours were categorised as benign, low- or high-aggressiveness cancer. Multivariate logistic regression was used to estimate the probability of the histological group by clinical and radiographic features in the entire cohort and a subcohort of cT1a tumours. The performance of the models was studied by calibration, Nagelkerke's R(2) , and discrimination (area under the receiver operating characteristic curve). RESULTS: The study cohort included 2 224 patients with a clinical stage I RM, of which 1 367 (61%) were cT1a. Benign lesions were found in 369 (16.6%), low-aggressiveness tumours in 1 156 (52%) and high-aggressiveness tumours in 699 (31.4%). Male gender, smoking history, increased tumour size, and lower exophytic rate were associated with malignancy and high-aggressiveness features (all P < 0.05). Models developed based on these characteristics had the ability to discriminate benign from malignant (bootstrap corrected c-index of 0.64) and high-aggressiveness tumours from benign and low-aggressiveness tumours (bootstrap corrected c-index of 0.66). Similar results were achieved in the cT1a subgroup. The c-index of tumour diameter as a single predictor of malignancy and high-aggressiveness tumours in the entire cohort was 0.6 and 0.63, respectively. CONCLUSION: Although older age, male gender, smoking history, increased tumour diameter, and reduced exophytic rate are associated with malignancy and high aggressiveness of clinical stage I RMs, models incorporating these characteristics have modest discriminating power, being only slightly better than the predictive ability of tumour size alone.

The role of diagnostic ureteroscopy in the era of computed tomography urography.

BACKGROUND: To examine the contemporary role of ureteroscopy in the diagnosis of upper urinary tract urothelial carcinoma. METHODS: We retrospectively evaluated 116 diagnostic ureteroscopies, performed in our institution to rule out primary UTUC. Demographics, cytological findings and interpretation of preoperative imaging were obtained. Ureteroscopic diagnosis and histological results were recorded and the predictive values of diagnostic studies were determined. Follow-up data was reviewed to evaluate the oncological outcomes in patients treated endoscopically. RESULTS: The pre-ureteroscopic evaluation included CTU in 91 (78%) patients. Positive and Negative predictive values of CTU were 76 and 80%, respectively. Typical filling defect on CTU was demonstrated in 38 of 89 patients. UTUC has been ruled out in 9 patients (24%) with suspicious filling defect on CTU. Endoscopic approach was implemented in 7 patients (18%). During a median follow up period of 17 months (IQR, 9-25) none of the followed patients experienced disease progression. CONCLUSIONS: Nephroureterectomy was spared from 42% of patients who underwent diagnostic ureteroscopy for suspected UTUC, demonstrated on CTU. In about half of those patients tumor has been ruled out and the others were managed endoscopically. Therefore, diagnostic ureteroscopy is advised as a crucial step in confirming UTUC and treatment planning.

Early discharge after laparoscopic or robotic partial nephrectomy: care pathway evaluation.

OBJECTIVE: To determine the success of our clinical care pathway for laparoscopic (LPN) and robotic partial nephrectomy (RPN) and to examine factors predictive for success. PATIENTS AND METHODS: A retrospective review of our Institutional Review Board-approved prospectively maintained minimally invasive PN database yielded 263 consecutive minimally invasive PNs from 2003 to 2010. Patient, disease and surgery-related factors were collected. The primary endpoint was successful implementation of the clinical pathway with discharge on postoperative day (POD 1). Associated factors were modelled using univariate and multivariable logistic regression to determine factors predictive for success of the pathway. RESULTS: Overall, 157 (60%) of the patients had successful care pathway implementation with POD1 discharge, of which 46 (17%) were RPNs. The overall readmission rate was 5% (12/263) and similar for patients discharged on POD 1, 4.5% (7/157). Several patient-related, tumour-related, and surgical factors were associated with care pathway success. In a multiple logistic regression model, only surgery period (late cohort vs early cohort) was significant for successful pathway implementation (odds ratio 4.2; 95% confidence interval 2.1-8.4, P < 0.001). CONCLUSIONS: Early discharge care pathways can be successfully implemented for LPN or RPN with low readmission rates. Care pathway success improves with institutional experience.

Natural history and health care burden of non-curative treatment for muscle-invasive bladder cancer.

OBJECTIVE: Muscle-invasive bladder cancer is an aggressive disease. Yet, many patients, especially those with advanced age and multiple comorbidities, do not receive treatment with curative intent. We evaluated the disease course and health care burden of these patients. MATERIALS AND METHODS: Bi-center, retrospective analysis of patients diagnosed with muscle-invasive bladder cancer who did not undergo curative-intent treatment (radical cystectomy or trimodal therapy) between 2016 and 2021. Patient characteristics and treatment burden were described. Metastasis-free, cancer-specific, and overall survivals were evaluated using the Kaplan-Meier method. RESULTS: Sixty-six patients with a median age of 86 (IQR 78,90) were evaluated. The median follow-up for survivors was 29 months (IQR 9, 44). All patients were diagnosed with muscle-invasive bladder cancer, and 32 (48%) presented with clinical T3 and T4 disease. The median age adjusted Charlson comorbidity index at diagnosis was 7 (IQR 6,8). Treatment with curative intent was not provided due to comorbidities and low-performance status in 58 patients (88%) and patient refusal in 8 (12%). Two-year estimated metastasis-free survival, cancer-specific survival, and overall survival were 11%, 18%, and 12%, respectively. During follow-up, 7 patients (10%) were treated with chemotherapy, 4 (6%) received immunotherapy, 21 (32%) radiation, and 17 (26%) had emergent operations due to hematuria. Twenty-four patients (37%) required nephrostomy tubes, and 39 (59%) required an indwelling urinary catheter for various periods. Forty-three patients (65%) suffered from recurrent hematuria episodes. Overall, median emergency room visits were 4 (IQR 2, 6), and median hospital admission was 16 days (IQR 9, 29). CONCLUSIONS: Untreated muscle-invasive bladder cancer is associated with a limited lifespan and a high disease burden for the patient and health system. These data should be taken into consideration and portrayed to the patient when curative intent treatment is chosen to be avoided.

Assessing the Impact of Percutaneous Nephrostomy Presence on Neoadjuvant Treatment Quality in Patients With Muscle Invasive Bladder Cancer.

INTRODUCTION: Symptomatic hydronephrosis associated with muscle invasive bladder cancer (MIBC) necessitates percutaneous nephrostomy (PCN) insertion before neoadjuvant chemotherapy (NAC). This study assesses the impact of PCN presence on standard intended NAC quality, its related complications and outcome after radical cystectomy (RC). MATERIALS AND METHODS: The study comprises a retrospective, multicenter cohort of 193 consecutive RCs performed between 2016 and 2019. Eighty (42%) of these patients received NAC and were divided in 2 comparison groups by presence (n = 26; 33%) or absence (n = 54; 67%) of PCN. Endpoints included completion of adequate NAC treatment (cisplatin-based chemotherapy for at least 4 courses), complications during NAC, post-RC complications and hospital stay. RESULTS: Overall, patients with PCN (45/193; 23%) featured a higher referral rate to NAC (58% vs. 36%, P = .01), worse glomerular filtration rates (P < .001) and more adverse events (P = .04), in comparison to non-PCN patients. In the NAC cohort, PCN patients had less adequate treatment rates (54% vs. 85%, P = .005), and more infections (35% vs, 7%; P = .008) and hospitalizations (58% vs. 13%; P < .001) during chemotherapy. Post-RC outcome was similar for both comparison groups. PCN was an independent risk factor for inadequate NAC (OR = 3.9, P = .04), and infections (OR = 11.3, P = .01) and hospitalizations (OR = 7.5, P = .004) during NAC. CONCLUSIONS: PCN in MIBC patients is a significant risk factor for inadequate NAC and adverse events during treatment. This finding may quire the rationale of NAC, potentially leading to consideration of NAC avoidance and upfront RC in PCN patients. Further survival studies with long follow-up are needed for elucidating this issue.

Differential use of partial nephrectomy for intermediate and high complexity tumors may explain variability in reported utilization rates.

PURPOSE: Partial nephrectomy has become a reference standard for tumors amenable to a kidney sparing approach but reported utilization rates vary widely. The R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and hilar tumor touching main renal artery or vein) nephrometry score was developed to standardize the reporting of tumor complexity with applicability in academic and community based settings. We hypothesized that tumor and surgeon factors account for variable use of partial nephrectomy. MATERIALS AND METHODS: Clinical and R.E.N.A.L. nephrometry score data were analyzed on 1,433 cases performed between 2004 and 2011 by a total of 19 surgeons with varying partial nephrectomy utilization rates (0% to 100%) who practiced at a total of 2 academic centers and 1 community based health system. RESULTS: Partial nephrectomy use increased during the study period from 36% before 2007 to 73% for 2010 to 2012 (p <0.0001). Increasing proportions of intermediate and high R.E.N.A.L. nephrometry score tumors were treated with partial nephrectomy during this time (35% to 86% and 11% to 36%, respectively, p <0.0001). Partial nephrectomy use was stable for low complexity tumors at 91% overall. Individual surgeons performed partial nephrectomy for 0% to 100% of intermediate complexity and 0% to 45% of high complexity tumors. On multivariable analysis surgery year, tumor size, each R.E.N.A.L. nephrometry score component, surgeon and annual surgeon volume predicted partial vs radical nephrectomy (each p <0.05). On multivariable analysis several surgeon factors, including surgeon volume, setting, fellowship training, and proportional use of minimally invasive and robotic partial nephrectomy, were associated with higher partial nephrectomy use (each p <0.002). CONCLUSIONS: Surgeon and tumor factors contribute significantly to the choice of partial nephrectomy. The significant variation in partial nephrectomy use by individual surgeons appears to be caused by differential treatment for intermediate and high complexity tumors. This may be due to surgical volume, training, setting and the use of minimally invasive techniques.

Prostate-specific antigen level association with COVID-19 infection and vaccination.

INTRODUCTION: The associations among SARS-CoV-2 infection, vaccination and total serum prostate serum antigen (PSA) levels in men undergoing screening for prostate cancer are unknown. METHODS: A retrospective analysis of data from a large health maintenance organization. Records of individuals aged 50 to 75 years with two serum PSA tests taken between March 2018 and November 2021 were included. Individuals with prostate cancer were excluded. Changes in PSA levels were compared between individuals who had at least 1 SARS-CoV-2 vaccination and/or infection between the two PSA tests and individuals who did not have an infection and were not vaccinated between the two PSA tests. Subgroup analyses were performed to assess the impact of the elapsed time between the event and the second PSA test on the results. RESULTS: The study and control groups included 6,733 (29%) and 16 286 (71%) individuals, respectively. Although the median time between PSA tests was shorter in the study vs. the control group (440 vs. 469 days, P<.001), PSA elevation between the tests was higher in the study group (0.04 vs. 0.02, P<.001). The relative risk for PSA elevation ≥1 ng/dL was 1.22 (95% CI 1.1, 1.35). Among individuals who were vaccinated, PSA increased by 0.03 ng/dL (IQR -0.12, 0.28) and 0.09 ng/dL (IQR -0.05, 0.34) after 1 and 3 doses, respectively (P<.001). Multivariate linear regression showed that SARS-CoV-2 events (ß 0.043; 95% CI 0.026-0.06) were associated with a greater risk for PSA elevation, after adjusting for age, baseline PSA and days between PSA tests. CONCLUSION: SARS-CoV-2 infection and vaccinations are associated with a slight increase in PSA, with the third anti-COVID vaccine dose having a more prominent impact, but its clinical significance is unknown yet. Any significant increase in PSA must be investigated and cannot be dismissed as secondary to SARS-CoV-2 infection or vaccination.