Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting.

Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erß), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen. Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERß. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERß positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERß-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERß-negative group (log-rank test P = 0.035). Conclusion: AR and ERß positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERß-positive tumors recurred as compared to AR-positive and ERß-negative patients. PFS was significantly lower in ERß-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

Potential role of 68Ga-PSMA PET/CT in metastatic renal cell cancer: A prospective study.

PURPOSE: Prostate-specific membrane antigen (PSMA), in addition to its utility in prostate cancer, is also an angiogenic imaging marker for hypervascular tumors like renal cell carcinoma (RCC). Our study aims to assess the potential role of 68Ga-PSMA-11 positron emission tomography (PET)/CT in metastatic RCC and compare it with contrast-enhanced computed tomography (CECT). METHODS: Biopsy-proven RCC patients with known or suspected distant metastases who underwent 68Ga-PSMA-11 PET/CT for staging/restaging were prospectively recruited. Those patients who had undergone 18F-FDG PET/CT within six weeks of 68Ga-PSMA PET/CT were also included retrospectively for comparative analysis. A patient-based and lesion-based analysis was done to compare the lesion detection rates of CECT, 68Ga-PSMA-11 PET and 18F-FDG PET. PET-based quantitative parameters were also compared between both the PET modalities. Impact of baseline parameters on survival was assessed using Cox regression analysis. A p-value of < 0.05 was considered significant. RESULTS: Thirty-seven patients with median age 60 years ± 13 years (range = 26-76 years) were included in the study. Twenty-seven patients had clear cell (cc) RCC, six had papillary RCC (pRCC), and one each had an eosinophilic variant of ccRCC, collecting duct RCC, translocation RCC and poorly differentiated RCC. 68Ga-PSMA-11 PET performed better in detecting marrow and equivocal bone lesions and worse in detecting liver lesions compared to CECT. 68Ga-PSMA-11 PET-based angiogenic tumor burden estimation using Total Lesion-PSMA (TL-PSMA) and PSMA-Total volume (PSMA-TV) had a prognostic impact on the survival of patients. 68Ga-PSMA-11 PET also detected more lesions and showed significantly higher SUVmax than 18F-FDG PET. CONCLUSION: 68Ga-PSMA-11 PET/CT performs better than CECT and 18F-FDG PET/CT in metastatic evaluation and has prognostic value in the management of clear cell RCC.

[177Lu]Lu-PSMA-617 Versus Docetaxel in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: Final Survival Analysis of a Phase 2 Randomized, Controlled Trial.

The prostate-specific membrane antigen (PSMA) inhibitor [177Lu]Lu-PSMA-617 has been previously demonstrated to be noninferior to docetaxel in achieving a biochemical response in chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Here, we report the final analysis of overall survival (OS) for a phase 2 randomized, controlled trial. Methods: Forty chemotherapy-naïve, PSMA-positive metastatic castration-resistant prostate cancer patients were randomly assigned to [177Lu]Lu-PSMA-617 (n = 20) or docetaxel (n = 20). Thirty-five patients received treatment per the protocol. Survival analysis was done using Kaplan-Meier curves and the Cox regression model. Results: The mean follow-up duration was 33.4 mo. In intention-to-treat analysis, the median OS for the [177Lu]Lu-PSMA-617 and docetaxel arms was 15.0 mo (95% CI, 9.5-20.5 mo) and 15.0 mo (95% CI, 8.1-21.9 mo), respectively (P = 0.905). In per-protocol analysis, the median OS was 19.0 mo (95% CI, 12.3-25.7 mo) versus 15.0 mo (95% CI, 8.1-21.9 mo), respectively (P = 0.712). No significant difference in OS was observed between the 2 arms across the analyzed subgroups. Conclusion: Long-term outcomes with [177Lu]Lu-PSMA-617 administered earlier in the prechemotherapy setting are comparable to those with docetaxel.

Robot-assisted partial nephrectomy for moderate to highly complex renal masses. A systematic review and meta-analysis.

Introduction: Multiple studies have been published recently assessing feasibility of robot-assisted partial nephrectomy (RAPN) for moderate to highly complex renal masses. Some studies have even compared partial nephrectomy (PN) performed through various modalities such as open PN (OPN) versus RAPN and laparoscopic PN (LPN) versus OPN. The primary aim of this review was to analyze perioperative outcomes such as warm ischemia time (WIT), duration of surgery, estimated blood loss (EBL), complications, blood transfusion, length of stay, and margin status following RAPN for complex renal masses. Another objective was to compare perioperative outcomes following various surgical modalities, i.e., OPN, LPN, or RAPN. Methods: Literature search was conducted to identify studies reporting perioperative outcomes following RAPN for moderate (Radius, Endophytic/Exophytic, Nearness, Anterior/posterior location [RENAL] score 7-9 or Preoperative Aspects of Dimension used for anatomic classification [PADUA] score 8-9) to high complexity renal masses (RENAL or PADUA score ≥ 10). Meta-analysis of robotic versus OPN and robotic versus LPN was also performed. Study protocol was registered with PROPSERO (CRD42019121259). Results: In this review, 22 studies including 2,659 patients were included. Mean duration of surgery, WIT, and EBL was 132.5-250.8 min, 15.5-30 min, and 100-321 ml, respectively. From pooled analysis, positive surgical margin, need for blood transfusion, minor and major complications were seen in 3.9%, 5.2%, 19.3%, and 6.3% of the patients. No significant difference was noted between RAPN and LPN for any of the perioperative outcomes. Compared to OPN, RAPN had significantly lower EBL, complications rate, and need for transfusion. Conclusions: RAPN for moderate to high complexity renal masses is associated with acceptable perioperative outcomes. LPN and RAPN were equal in terms of perioperative outcomes for complex masses whereas, OPN had significantly higher blood loss, complications rate, and need for transfusion as compared to RAPN.

[68 Ga]Ga-PSMA-11 Small Bowel Uptake in Crohn's Disease: Revisiting the "Non-specificity" of PSMA Ligands.

The rapidly evolving clinical utility of prostate-specific membrane antigen (PSMA) PET/CT as an imaging modality for prostate cancer (PCa) has brought to the forefront a multitude of non-prostatic diseases also exhibiting PSMA radioligand uptake. We report a case of a 71-year-old male with PCa who underwent PSMA PET/CT for recurrence evaluation. The scan demonstrated [68 Ga]Ga-PSMA-11 uptake in the distal ileum. Retrospective enquiry revealed that the patient was a known case of Crohn's disease. This case highlights an uncommon finding of PSMA radioligand uptake in the distal small bowel (non-prostatic benign pathological uptake) in a patient with known Crohn's disease, which may be misinterpreted in the evaluation of PCa.

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial.

PURPOSE: Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients. METHODS: This was a randomized, parallel-group, open-label, phase 2, and non-inferiority trial. Chemotherapy-naïve patients with mCRPC and high PSMA-expressing lesions on 68 Ga-PSMA-11 PET/CT were randomly assigned in 1:1 ratio to 177Lu-PSMA-617 (6.0-7.4 GBq/cycle, every 8 weeks, up to 4 cycles) or docetaxel (75 mg/m2/cycle, every 3 weeks, up to 10 cycles). The primary end-point was best prostate-specific antigen response rate (PSA-RR), defined according to Prostate Cancer Clinical Trials Working Group-3 as proportion of patients achieving ≥ 50% decline in PSA from baseline. Non-inferiority margin of - 15% was pre-specified for PSA-RR. RESULTS: Between December 2019 and March 2021, 40 of the 45 patients assessed for eligibility underwent randomization. Fifteen of 20 patients in 177Lu-PSMA-617 arm and 20/20 patients in docetaxel arm received treatment per protocol. Of these, best PSA-RR in the 177Lu-PSMA-617 arm was 60% (9/15) versus 40% (8/20) in the docetaxel arm. The difference in the PSA-RRs between the two arms was 20% (95% confidence interval, CI: - 12-47, P = 0.25), meeting the pre-specified criterion for non-inferiority in per-protocol analysis. Further, progression-free survival rates at 6 months were 30% and 20% in the 177Lu-PSMA-617 and docetaxel arms respectively (difference 10%, 95% CI: - 18-38, P = 0.50). Overall, treatment-emergent grade ≥ 3 adverse events occurred less frequently with 177Lu-PSMA-617 than with docetaxel (6/20, 30% versus 10/20, 50%, respectively, P = 0.20). Quality-of-life outcomes improved significantly in 177Lu-PSMA-617 arm compared to docetaxel arm (P < 0.01). CONCLUSION: 177Lu-PSMA-617 was demonstrated to be safe and non-inferior to docetaxel in the treatment of mCRPC and could, thus, be potentially employed earlier in the disease course rather than being solely reserved for advanced end-stage disease. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India, CTRI/2019/12/022282.

Robot-assisted Repair of Complex Vesicovaginal Fistulae: Feasibility and Outcomes.

OBJECTIVE: To share our experience and techniques of robot-assisted repair of complex vesicovaginal fistulae. METHODS: Prospectively maintained data of patients undergoing robot-assisted repair of complex vesicovaginal fistula (VVF) from December 2014 to October 2019 were analyzed. Patient characteristics, operative data, postoperative events, and follow-up outcomes were noted. All cases underwent preoperative cysto-vaginoscopy and upper tract imaging. The procedure was completed in a standard fashion. Additional procedures included Boari flap reimplantation, Burch-colposuspension, ureteric reimplantation and Vaginal flap incorporation. On follow-up, successful repair was defined as no urine leak after removal of catheter. RESULTS: Out of 73 patients undergoing robot-assisted VVF repair at our institute, 33 were classified as complex VVF. Mean age was 42.7 ± 7.2 years. The most common cause of VVF was posthysterectomy (81.8%) with 21 (63.1%) recurrent VVFs. Thirty patients (90.0%) had supratrigonal fistulae; multiple fistulae were present in 3 cases. Two patients underwent Boari flap ureteric reimplantation for concomitant ureteric stricture and ureteric neocystostomy was required in another patient. One patient underwent our novel technique of vaginal flap incorporation and a Burch colposuspension was performed simultaneously in one patient with stress incontinence. The median follow-up was 35 months (interquartile range 8.5months). Successful outcome was noted in 31 (93.9%) patients; recurrence requiring further repair in 2 patients. CONCLUSION: The current series presents the largest number of complex VVFs repaired by robotic assistance. Robot-assisted repair can be considered as one stop procedure for such complex and vexing problems.

Health-Related Quality-of-Life Outcomes with Actinium-225-Prostate-Specific Membrane Antigen-617 Therapy in Patients with Heavily Pretreated Metastatic Castration-Resistant Prostate Cancer.

AIMS: Actinium-225 (225Ac) labeled prostate-specific membrane antigen (PSMA)-617 is a novel treatment modality in the management of metastatic castration-resistant prostate cancer (mCRPC). The present study was conducted to assess the impact of 225Ac-PSMA-617 therapy on the quality-of-life of patients with heavily pretreated mCRPC using the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Prostate Symptom Index-17 (NCCN-FACT-FPSI-17) questionnaire. MATERIALS AND METHODS: This was a retrospective single-center study where data of consecutive heavily pretreated mCRPC patients treated with 225Ac-PSMA-617 from January 2019 to February 2020, was collected and analyzed for the biochemical response, quality-of-life outcomes and treatment-related toxicity. RESULTS: Eleven heavily pretreated mCRPC patients received a median cumulative dose of 8.3 MBq (interquartile range [IQR] 5.6-20.4 MBq) 225Ac-PSMA-617 over 1-4 cycles. 5/11 patients (46%) showed a ≥50% decline in Prostate Specific Antigen (PSA), while stable values and PSA progression were observed in 3/11 (27%) patients each. Pre- and post-therapy NCCN-FACT-FPSI-17 questionnaires revealed statistically significant improvement in the total FPSI score (P = 0.003) as well as the disease-related symptoms-physical (P = 0.004) and disease-related symptoms-emotional (P = 0.046) subscores. Among the physical symptoms, significant improvement was noted with respect to pain, difficulty in urination, bone pain, fatigue, and restriction in physical activity. No significant change was noted in the treatment side-effects subscore. Of the treatment-related adverse effects, Grade 3 dryness of the mouth, anemia, and nephrotoxicity was observed in 1/11 patients (9%) each and Grade 3 thrombocytopenia in 2/11 patients (18%). CONCLUSION: Health-related quality-of-life of the mCRPC patients improved significantly with 225Ac-PSMA-617 despite extensive pretreatment and advanced nature of the disease.

Robot-Assisted Nephron-Sparing Surgery of Renal Hydatid in Pregnancy: A Predicament in Management.

Background: Hydatid disease is a parasitic zoonosis caused by Echinococcus granulosus. Dog and other carnivores are the definitive hosts, which harbor adult worm. Humans are the accidental and dead-end hosts that acquire the infection by ingestion of eggs released from the intestinal tract of these carnivores, mainly dogs. The primary organ of echinococcosis in humans is the liver and lung, while the kidney is the third most commonly involved organ. Occurrence of hydatid disease of kidneys in isolation or with multiple organ involvement and their management has been reported and well described. The concurrent hydatidosis and pregnancy are an unusual clinical condition and poses a clinical challenge. Case Details: In this study, we present a case of 36-year-old woman with symptomatic hydatid disease of the right kidney during the first trimester of pregnancy. A multidisciplinary team discusses the pros and cons of hydatid during pregnancy with the patient. After taking informed consent from the patient, she was effectively managed by medical termination of pregnancy followed by robot-assisted laparoscopic pericystectomy. Conclusion: The co-occurrence of symptomatic renal hydatid and pregnancy is quite unusual. Medical or surgical management of hydatid during pregnancy can have some detrimental effect on the fetus. Hence these patients could be managed with medical termination of pregnancy followed by robot-assisted nephron-sparing surgery. Robot-assisted surgery for the renal hydatids is safe and effective, and has a shorter learning curve.

Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis.

INTRODUCTION: Programmed cell death-1/programmed cell death ligand-1 (PD-1/PDL-1) inhibitors are the newest class of approved drugs for advanced urothelial cancer (AdUC). This review aims to collate the evidence for their efficacy and safety in various treatment settings. METHODS: Extensive search of databases was performed (updated May 2018) and the protocol was registered on PROSPERO (CRD42017081568). The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. STATA (v 12) and Revman 5.3.5 were used for data analysis. RESULTS: Ten nonrandomized, open-label clinical trials were included in this review. PD-1/PD-L1 inhibitors were used as second-line, stand-alone in eight trials and as first-line in cisplatin-ineligible in two trials. Heterogeneity was observed for study design, PDL-1 testing methods, cutoff criterias used and translational markers evaluated. The pooled objective response rate (ORR) was 18.2% (95% confidence interval [CI] 15.1-21.2, n = 1785) with PD-1/PDL-1 inhibitors in second-line settings as compared to 12.6% (95% CI 10.3-14.9, n = 736) with second-line chemotherapy and 23.7% (95% CI 19.9-27.4, n = 489) with PD-1/PDL-1 inhibitors as first-line therapy in cisplatin-ineligible patients. The median progression-free survival and overall survival was similar with PD-1/PD-L1 inhibitors in both second- and first-line treatment settings (1.5-2.9 vs. 2.0-2.7 months and 7.9-18.2 vs. 15.9 months) and second-line chemotherapy (3.3-4.0 months and 7.4-8 months). Odds of achieving ORR was 0.10 (95% CI 0.03-0.31, n = 229) in the second-line, stand-alone setting with a combined positive score (CPS) cutoff of 25% and was 0.34 (95% CI 0.19-0.62, n = 265) with a CPS cut-off of 10% in first-line setting in the cisplatin-ineligible. CONCLUSIONS: PD-1/PDL-1 inhibitors appear to be promising in the treatment of AdUC and CPS may be a potentially reliable biomarker for predicting response but needs validation. Caution needs to be exercised until more data are available on imAEs and further studies are required to prove their worth as the standard of care.

Protocol-based perioperative antimicrobial prophylaxis in urologic surgeries: Feasibility and lessons learned.

INTRODUCTION: Rational use of antibiotics and strict adherence to practice guidelines is essential to prevent antibiotic resistance. The best surgical prophylaxis protocol requires tailoring of the available guidelines in accordance to the local bacterial flora. We designed a protocol for surgical prophylaxis to check the rampant abuse of antibiotics in the department of urology and evaluated its feasibility. MATERIALS AND METHODS: Patients admitted for elective major surgeries under a single unit of our department over a period of 5 months were included in the study. A protocol for antibiotic prophylaxis was designed based on the European Association of Urology guidelines and the local hospital antibiogram. Single-dose intravenous cefuroxime was administered to the patients undergoing clean and clean-contaminated surgeries. Extended protocols were formulated for contaminated surgeries. Postoperative course and complications were recorded. Effectiveness was defined as adherence to the protocol (without an addition or a change in antibiotic regimen) along with an uneventful postoperative course. Prospectively maintained data were analyzed using descriptive statistics. RESULTS: Data of 277 patients were analyzed. The mean age was 48.37 ± 17.39 years and 27.1% had comorbidities. Majority of the surgeries were clean contaminated (81%), and 60.3% of the total were endoscopic. The protocol was effective in 89.5% of the patients (248/277). The failure rate was higher for the contaminated procedures (41.7%) (odds ratio - 6.43; confidence interval = 1.51-27.2, P < 0.001). Post-operative sepsis with or without shock was the commonest cause (16/29, 55.2%) of protocol failure. Fourteen out of the 16 patients who developed sepsis had undergone endourological surgeries. CONCLUSIONS: Protocol-based perioperative antibiotic prophylaxis in urological surgeries is feasible. Similar protocols should be developed and validated at other major centers to limit the unnecessary use of antibiotics and prevent the emergence of antibiotic resistance.

Efficacy of tamsulosin and tadalafil in relieving benign prostatic hyperplasia related symptoms: A randomized double blind placebo controlled cross-over study.

INTRODUCTION: Tadalafil and Tamsulosin have both been approved for use in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). This study compared the differential effects of these two on BPH-LUTS using a cross over study design. METHODS: Men ≥45 years of age, with an International Prostate Symptom Score (IPSS) ≥8 due to BPH-LUTS were included. The patients were randomized into sequence AB (tadalafil 10 mg OD followed by tamsulosin 0.4 mg OD) or BA in a double blind manner. All patients received a placebo lead-in period for 2 weeks, followed by an active drug for 6 weeks; placebo wash out for 4 weeks and then crossed over to second active drug for another 6 weeks. IPSS scores, Uroflowmetry parameters and International Index of Erectile Function-5 scores were recorded. RESULTS: Out of the 40 patients, 36 completed the study. Demographic and baseline characteristics were comparable between the two groups (AB and BA). No significant placebo effects were observed. Tadalafil and tamsulosin significantly improved the total IPSS score and quality of life (P < 0.05) as compared to the baseline. However, there were no significant differences between the two drugs with respect to extent of observed effect and which drug was prescribed 1st in the sequence respectively (P > 0.05). Significant period effect was observed (P < 0.05) i.e., the symptoms did not return to the baseline before the second treatment. Half of the nonresponders to either of the drugs responded when the drug was changed to the other. Tadalafil showed better improvement in EF score as compared to Tamsulosin. CONCLUSION: Both Tadalafil and Tamsulosin improved LUTS and erectile function and those patients who did not respond to Tadalafil showed improvement with Tamsulosin and vice-a-versa.

Prominent swelling on erection: Perineal angiomyxoma as a rare entity.

Perineal angiomyxoma is a rare entity, more commonly seen in females. We report a case of a 44 year old male who presented with a perineal swelling which became prominent with penile erections. Magnetic Resonance Imaging (MRI) revealed a T1 hypointense and T2 hyperintense midline lesion (4.6 × 2.5 × 5 cm) in relation to corpus spongiosum, with ill defined fat planes with the bulbospongiosus muscle and progressive enhancement on dynamic contrast sequence. A differential diagnosis of soft tissue sarcoma or hemangioma was made and the mass was completely excised via a midline perineal incision. The histopathology revealed features consistent with angiomyxoma.

Utility of restage transurethral resection of bladder tumor.

INTRODUCTION: Transurethral resection of bladder tumor (TURBT) aims at complete resection of all the visible tumors. Existing guidelines recommend restage TURBT in all patients with T1 and high-grade tumors, to avoid under-staging. However, restage TURBT may not be plausible/feasible at all the times. This study was performed with an aim to better define the utility of restage TURBT in a tertiary care hospital of India. METHODS: Patients with high grade/T1 tumors at the first TURBT were prospectively enrolled. Their demographic profile, previous cystoscopic findings, and histological reports were recorded. The primary objective was to assess the tumor detection and stage up-migration rates at restage TURBT. The secondary objectives was to identify factors predicting presence of tumor at restage TURBT. Patients were followed up to detect recurrence and progression for a minimum of 3 months. RESULTS: Of 128 prospective patients' enrolled, 29 patients were lost to follow-up and 11 patients did not undergo restage. A total of eighty-eight patients underwent restage TURBT of which twenty-eight patients (31.8%) had tumor at their second TURBT with five of these patients being upstaged to T2. The risk of having a tumor at restage was significantly higher in patients with solid tumors (56.2% vs. 26.4%, P = 0.02, 95% confidence interval: 0.035-0.024) but was independent of the tumor size (P = 0.472), number of growths (P = 0.267), grade of tumor (P = 0.441), presence or absence of muscle at the initial TURBT (P = 0.371) and place of initial TURBT (P = 0.289). There was a significant difference in the recurrence and progression rates in patients who had tumor at restage as compared to those who did not (recurrence; 33.3% and 23.8%, P = 0.022, respectively vs. progression; 11.1% and 3.7% respectively, P = 0.07; mean follow-up = 10.8 months). CONCLUSIONS: We conclude that restage TURBT is necessary in patients with solid looking tumors and the presence of tumor at restage confers a higher risk of recurrence and progression.