Utility of PSMA-PET derived volumetric parameters in initial risk stratification and prediction of prostate cancer metastasis - a head-to-head comparison of the radiotracers 18F-PSMA-1007 and 68Ga-PSMA-11.

OBJECTIVE: This study aimed to explore and compare the utility of baseline 18F-PSMA-1007 and 68Ga-PSMA-11 PET/computed tomography (CT) derived volumetric parameters in initial risk stratification and prediction of prostate cancer (PCa) metastasis. METHODS: Forty treatment-naïve, biopsy-proven intermediate-/high-risk PCa patients were prospectively recruited. Each patient underwent PET/CT with 68Ga-PSMA-11 and 18F-PSMA-1007 (within 2 weeks). The maximum and mean standardized uptake values (SUVmax and SUVmean) of primary tumor, prostate PSMA-tumor volume (PSMA-TVp), and prostate total lesion PSMA (TL-PSMAp) were measured. RESULTS: PSMA-TVp and TL-PSMAp (with both radiotracers) mostly exhibited moderate-to-strong correlation with Gleason score, serum prostate-specific antigen level and clinical tumor stage (Spearman ρ = 0.361-0.783, P-values ≤0.022). Primary tumor SUVmax values were similar across initial risk categories. PSMA-TVp and TL-PSMAp, however, were significantly higher in high-risk PCa compared to intermediate-risk PCa (P-values ≤0.001). Receiver operating characteristic (ROC) curve analysis revealed that F-PSMA-TVp, Ga-PSMA-TVp, F-TL-PSMAp, and Ga-TL-PSMAp (optimal cutoff values of 20.9, 23.4, 142.5, and 144.8, respectively) could effectively differentiate high-risk from intermediate-risk PCa [area under the ROC curve (AUCs) 0.859-0.898, P-values <0.001] with high sensitivity (~68.8-75%) and excellent specificity (100%). PSMA-TVp and TL-PSMAp (with both radiotracers) could predict presence of regional and extraregional nodal metastasis (AUCs 0.703-0.801, P-values ≤0.03) with moderate sensitivity (~47.8-70.6%) and excellent specificity (~82.6-94.1%). CONCLUSION: Our results suggest that baseline PSMA-PET primary tumor volumetric parameters provide a noninvasive, objective, and accurate index for initial risk stratification and can predict presence of regional and extraregional nodal metastasis in PCa patients. Larger studies are warranted to evaluate their incremental role over conventional parameters.

Prognostic significance of Klotho expression in patients with renal cell carcinoma.

INTRODUCTION: Various molecular markers have been investigated in renal cell carcinoma (RCC) without significant reliability. We analyzed Klotho (tumor suppressive protein) expression in RCC to investigate its association with tumor-stage, grade, disease-free-survival (DFS) and overall-survival (OS). METHODS: Data of histologically confirmed patients of RCC with complete clinical follow-up were retrieved from Medical-Record-Library. Tissue sections of tumor and normal parenchyma were prepared from the blocks. Immunohistochemical studies for Klotho were done with commercially available kit (EPR6856, Ab181373; Abcam, Cambridge MA, USA). Klotho expression was scored between 0-3 and grouped into weak/absent (0, 1) and moderate/strong (2, 3). Tumors stages and grades were grouped into low stage (I and II) and high stage (III and IV) and into low grade (grade 1 and 2) and high grade (grade 3 and 4) according to WHO/ISUP grading. The histopathologists were blinded as to the clinical and follow-up data. Various prognostic factors were analyzed with respect to Klotho expression. Kaplan-Meier curves were created for DFS and OS. RESULTS: Fifty-four patients of mean age 55.15 ± 13.34 years and M:F ratio of 1.8:1 were included. Normal renal tissue had strong expression of Klotho in all. In tumor tissue 20 (37%) had negative, 7 (13%) had weak, 14 (25.9%) had moderate and 13 (24.1%) had strong Klotho expression. Significantly more patients had absent/weak Klotho expression with higher grade (16/24 (66.7%) vs 7/25 (28%); p = 0.007), higher stage (22/33 (66%) vs 5/21 (23.8%); p = 0.002), LVI (12/14 (85.7%) vs 2/14 (14.3%); p = 0.002), sinus-fat-invasion (16/21 (76.2%) vs 5/21 (23.8%); p = 0.002), renal-vein-involvement (14/18 (77.8%) vs 4/18 (22.2%); p = 0.004), necrosis (17/26 (65.3%) vs 9/26 (34.6%); p = 0.029) and metastasis (8/9 (88.9%) vs 1/9 (11.1%); p = 0.01). Median DFS and OS were significantly lower in patients with weak/absent Klotho expression (12 vs 23 months, p = 0.023 and 15 vs 33 months, p = 0.006 respectively). Kaplan-Meier curves showed lower estimated DFS and OS in patients with weak/absent expression. CONCLUSIONS: We conclude that Klotho expression in renal tumor could be a good prognostic marker in patients with 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.

Evaluation of an automated rapid urine culture method for urinary tract infection: Comparison with gold standard conventional culture method.

PURPOSE: Urinary tract infection is one of the most prevalent disease affecting people from all age groups. For its diagnosis, conventional culture and antibiotic susceptibility is the gold standard. However, its major limitation is that the results take minimum of 24 â€‹h and antibiotic susceptibility is available after 48 â€‹h. Automated culture methods having comparable sensitivity and specificity as compared to conventional culture should be evaluated for routine diagnostics. With this aim we evaluated the diagnostic accuracy of automated urine culture method HB&L uroquattro by comparing with the gold standard conventional culture method. MATERIALS AND METHODS: A total of 1220 urine samples were included in the study. Semi-quantitative urine culture was performed using standard methods on cysteine lactose electrolyte deficient medium. For the automated culture, HB&L Uroquattro (Alifax, Polverara, PD, Italy), standard guidelines given in the manual of the instrument were followed. Diagnostic performance in terms of sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values were calculated. RESULTS: Based on the final interpretation of conventional culture for the total 1220 samples, 26 samples (2.1%) showed major non-concordance as they were identified as sterile by HB&L but had significant growth by conventional culture and 19.9% showed minor non-concordance. At 100-999 colony forming unit/ml, HB&L has high negative predictive value i.e. 96.6% with 95% CI (95.2%-97.6%) and sensitivity i.e. 92.66% with 95% CI of (89.42%-95.15%). CONCLUSION: The HB&L Uroquattro seems to be a reliable instrument to obtain urine microbiological results in a timely manner. This technique can give presumptive report to the clinician within 5 â€‹h only for initiation of empirical antibiotics in cases of positive results.

Effect of ureteric access sheath on outcomes of retrograde intrarenal surgery for renal stone disease: a randomized controlled trial.

BACKGROUND: The need of ureteric access sheath (UAS) in retrograde intrarenal surgery (RIRS) has been controversial for gaining high success in terms of stone free rate (SFR), reducing operative times and complications. There has been lack of high level of evidence in the literature on this topic. MATERIALS AND METHODS: This prospective randomized controlled trial (RCT) was conducted in the Department of Urology, PGIMER, Chandigarh from July 2019 to Dec 2021. The effect of UAS on the outcome of RIRS (SFR, operative time and complications) for renal stone disease was assessed. Ninety patients were randomized into two groups: 41 patients in Group 1 (RIRS with UAS) and 40 patients in Group 2(RIRS without UAS) were finally analyzed after exclusion. All the patients underwent preoperative double J stent placement at least 10 days prior to the definitive procedure. Operative time was recorded and postoperative pain was assessed by visual analogue scale(VAS) at 6 and 24 h postoperatively. Complications and emergency visits were recorded up to one month post procedure. SFR was assessed at 1 month using noncontrast CT KUB. Success was defined as absence of any residual fragment more than 3 mm in maximum diameter. RESULTS: Demographic parameters (age, body mass index, and comorbidities) and preoperative parameters (stone burden, proportion of recurrent stone formers and proportion of patients with inferior calyceal stones) were comparable between the two groups. Operative times (45.49 vs 48.38 min; p - 0.484) and VAS scores at 6 and 24 h post-op (p - 0.577) were also comparable between Group 1 and Group 2. SFR was comparable in Group 1 and Group 2 (78.05% vs 80%, p - 0.829). Postoperative complications were higher in the UAS group, but not statistically significant (4.88% vs 0%; p - 0.157). CONCLUSION: The use of UAS during RIRS is not associated with improved SFR. RIRS can be performed safely without the use of UAS and without increasing postoperative complications.

Comparison of 18 F-PSMA-1007 PET/CT With 68 Ga-PSMA-11 PET/CT for Initial Staging in Intermediate- and High-Risk Prostate Cancer.

PURPOSE: This study aimed to compare 18 F-PSMA-1007 PET/CT with 68 Ga-PSMA-11 PET/CT for initial staging in intermediate- and high-risk prostate cancer (PCa) patients. METHODS: Forty treatment-naive, biopsy-proven, intermediate- or high-risk PCa patients were prospectively recruited. Each patient underwent PET/CT with 68 Ga-PSMA-11 and 18 F-PSMA-1007 (within 2 weeks). Assessment of both set of images included delineating number and characteristics of lesions, measurement of tracer uptake (SUV max ), miPSMA scoring, and PET-based stage categorization. RESULTS: Intraprostatic lesions were detected in all patients by both tracers with concordant PET-based T stage. Median SUV max of the dominant PSMA-positive prostatic lesions was not significantly different with 18 F-PSMA-1007 and 68 Ga-PSMA-11 (19.9 vs 19.4, P = 0.127, n = 40). Prostatic miPSMA scores were similar in 31/40 (77.5%) patients with both tracers (weighted κ = 0.71). In 23/40 (57.5%) patients, regional lymph nodes (n = 171) were detected by both tracers. Few additional PET-positive regional lymph nodes (n = 3) were exclusively detected by 18 F-PSMA in 2 patients without altering PET-based N stage. Extraregional lymph nodes (n = 123 in 17/40 patients) and visceral metastatic lesions (n = 18 in 3/40 patients) were detected concordantly by both tracers. PET-positive marrow based and skeletal metastases (n = 71) were detected in 14/40 (35%) patients by both tracers. Few additional marrow and skeletal lesions (n = 7) were exclusively detected on 18 F-PSMA-1007 in 5/14 patients, potentially upstaging PET-based M stage in 2/5 patients. Both radiotracers showed excellent interreader agreement for region-wise detection of lesions. CONCLUSIONS: Our results suggest that 18 F-PSMA-1007 PET/CT is comparable to 68 Ga-PSMA-11 PET/CT in detecting primary and metastatic lesions of PCa.

Iatrogenic partial glanular amputation: A rare complication of circumcision.

Circumcision is a customary ritual across many cultures. However, the safety of such procedures remains a concern. A boy underwent circumcision in 2014 by a religious worker at the age of 7 years. Post circumcision, the patient had gradual narrowing of the penis, between the glans and the shaft, with an iatrogenic partial glanular amputation and presented to us at the age of 14 years. The patient underwent end-to-end urethroplasty and glansplasty. Postoperatively, the patient did well and the wound remained healthy. Circumcision has complications even in expert hands. Religious circumcision can result in dreadful complications in children and adolescents.

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.

Impact of pathological factors on survival in patients with upper tract urothelial carcinoma: a systematic review and meta-analysis

ABSTRACT Introduction: There is an ongoing need to identify various pathological factors that can predict various survival parameters in patients with upper tract urothelial carcinoma (UTUC). With this review, we aim to scrutinize the impact of several pathological factors on recurrence free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) in patients with UTUC. Materials and Methods: Systematic electronic literature search of various databases was conducted for this review. Studies providing multivariate hazard ratios (HR) for various pathological factors such as tumor margin, necrosis, stage, grade, location, architecture, lymph node status, lymphovascular invasion (LVI), carcinoma in situ (CIS), multifocality and variant histology as predictor of survival parameters were included and pooled analysis of HR was performed. Results: In this review, 63 studies with 35.714 patients were included. For RFS, all except tumor location (HR 0.94, p=0.60) and necrosis (HR 1.00, p=0.98) were associated with worst survival. All the pathological variables except tumor location (HR 0.95, p=0.66) were associated with worst CSS. For OS, only presence of CIS (HR 1.03, p=0.73) and tumor location (HR 1.05, p=0.74) were not predictor of survival. Conclusions: We noted tumor grade, stage, presence of LVI, lymph node metastasis, hydronephrosis, variant histology, sessile architecture, margin positivity and multifocality were associated with poor RFS, CSS and OS. Presence of CIS was associated with poor RFS and CSS but not OS. Tumor necrosis was associated with worst CSS and OS but not RFS. Tumor location was not a predictor of any of the survival parameters.

Long-term impact of testicular torsion and its salvage on semen parameters and gonadal function.

Introduction: Testicular torsion is a urological emergency, and long-term outcomes of testicular torsion on infertility, hormonal function, and salvaged testicular size are unclear. Materials and Methods: We conducted an ambispective, observational study from January 2014 to December 2019. Baseline demographics, time of presentation, clinical features, and management details of all the patients of testicular torsion were recorded from the database. All the patients were followed up in the outpatient clinic for testicular size, hormone levels, semen analysis, and erectile function. Results: Of 85 patients, only 67 could be contacted and included in the final analysis. Group 1(orchiectomy) comprised 44 patients, and Group 2(salvage) had 23 patients. Follow-up duration ranged from 2 to 6 years and mean follow-up was 42 ± 12 months. The median time to presentation was significantly higher in Group 1 (48 hours) as compared to Group 2 (12 hours). The rate of testicular salvage did not vary with age of the patients. Doppler ultrasonography of the scrotum detected 92.5% of all cases of torsion. Antisperm antibody levels were within normal range in all patients. Approximately 47% of patients in the salvage group developed testicular atrophy on follow-up. Serum testosterone level was significantly lower in Group 1 and the subset of patients with testicular atrophy. Rest of the hormonal parameters, semen analysis, and erectile function were comparable between two groups. Conclusion: The time between onset and presentation is an important contributing factor in guiding testicular salvage. Even after salvage, many testes may atrophy on follow-up. Orchiectomy and testicular atrophy in the long term have negative impact on serum testosterone. The patients should be counseled for a long-term follow-up for the risk of testicular atrophy and low testosterone levels.

Current practice patterns in the perioperative management of patients undergoing radical cystectomy: Results from a global survey.

OBJECTIVE: To determine current practice patterns and adherence to various components of enhanced recovery after surgery in cystectomy (ERAC) protocol for peri-operative management of radical cystectomy patients through a global survey. METHODS: A survey containing 25 questions and addressing 15 of the 22 items of the ERAC protocol was developed and disseminated through Email to the urologists with recent bladder cancer publications. The mailing list was generated by retrieving Email-ids of corresponding authors of articles using the keyword "cystectomy" in Scopus from January 2018 to October 2020. RESULTS: The survey was completed by 443 respondents across the globe. About 51.5% of respondents used some form of bowel preparation. A minority used carbohydrate loading (29.8%) and Alvimopan (13.3%). A short duration of nil by mouth was practised by 28.9%. For antibiotic prophylaxis, 51.7% used one, and 42% used two antibiotics. Duration of antibiotics was 24 hours, 48 hours, and >48 hours for 47.6%, 16.9%, and 35.4%, respectively. For peri-operative analgesia, 43.6% used non-steroidal anti-inflammatory drugs, 9.3% opioids and 40.6% combination of both. Pharmacological thrombo-prophylaxis was routinely used by 74.7% respondents. There was significant variability in ERAC and non-ERAC components according to region of practice; The open surgical approach was most commonly used in Africa (92%), whereas it was the robotic approach in North America (or America?) (41%). The use of bowel preparation was higher in Asia (58%) and Africa (65%). Alvimopan use was more common in North America (58%). Most used 1 or 2 prophylactic antibiotics but the duration was shorter (<24 hours) in the Americas and European (58%-83%) compared to Asia and Africa (15%-35%). CONCLUSION: There is high variability in the use of different ERAC components. Other than the timely removal of the abdominal drain and the use of thromboprophylaxis, the overall adherence of ERAC components is low.

68Ga-PSMA-11 uptake in tracheal mucus plug - a potential pitfall.

Prostate-specific membrane antigen (PSMA) PET/CT is a well-acclaimed imaging modality for prostate cancer (PCa). However, many reports have highlighted PSMA radioligand uptake in a variety of benign tumors and lesions. We report a case of PCa in which 68 Ga-PSMA-11 uptake was noted in the tracheal lumen. However, 18F-PSMA-1007 PET/CT was done on a subsequent day, which demonstrated no abnormal radiotracer uptake or morphological lesion within the tracheal lumen. This case highlights an uncommon finding of PSMA ligand uptake in a tracheal mucus plug (non-prostatic benign uptake), which may be misinterpreted as a false-positive finding.

Safety and Diagnostic Yield of 68Ga Prostate-specific Membrane Antigen PET/CT-guided Robotic-assisted Transgluteal Prostatic Biopsy.

Background Transrectal US-guided biopsy with or without MRI fusion is performed for diagnosing prostate cancer (PCa) but has limitations. Gallium 68 (68Ga) prostate-specific membrane antigen (PSMA) PET/CT-guided targeted biopsy has the potential to improve diagnostic yield of PCa. Purpose To evaluate the safety and diagnostic yield of 68Ga PSMA PET/CT-guided, robotic-arm assisted transgluteal prostatic biopsy. Materials and Methods In this single-center nonrandomized prospective trial, participants with a clinical suspicion of PCa (serum prostate-specific antigen level > 4 ng/mL) were recruited from January 2019 to September 2020. After whole-body 68Ga PSMA PET/CT, participants with PSMA-avid intraprostatic lesions underwent PET-guided transgluteal biopsy by using an automated robotic arm. To assess safety and diagnostic yield, procedure-related complications and histopathologic results were documented. Pain during the procedure was scored by a visual analog scale. Descriptive statistics were applied; qualitative variables were reported in percentages. Results Seventy-eight participants (mean age, 66 years ± 7 [standard deviation]; 36 participants [46%] with prior negative results at transrectal US-guided biopsy) were enrolled. Fifty-six (72%) participants had PSMA-avid lesions (prior negative results at transrectal US-guided biopsy in 22 of 56 [39%]) and underwent targeted biopsy. PCa was confirmed in 54 of 56 (96%) participants, and clinically significant PCa (Gleason score ≥ 7) was confirmed in 24 of 54 (44%). Two participants had nonrepresentative samples that required rebiopsy. All participants experienced pain during the procedure, mild (median visual analog scale score, 1; interquartile range, 1-2) in 36 of 56 (64%) and moderate (median visual analog scale score, 5; interquartile range, 5-6) in 20 of 56 (36%). Postprocedure complications were noted in five of 56 (9%) participants and were minor (hematuria, four participants; hematospermia, one participant; and gluteal pain, two participants). No participant developed a postprocedural infection. Conclusion Transgluteal prostate-specific membrane antigen (PSMA) PET/CT-guided, robotic-targeted prostatic biopsy is safe with a high diagnostic yield of prostate cancer for PSMA-avid lesions. Clinical trial registration no. NCT05022576 © RSNA, 2022.

Xpert bladder cancer monitor in surveillance of bladder cancer: Systematic review and meta-analysis.

INTRODUCTION: There is a need for sensitive and specific biomarkers for detecting recurrences in patients with non-muscle invasive bladder cancer (NMIBC) on surveillance. Xpert bladder cancer (BC) monitor is the latest rapid in vitro qualitative test that detects expression of 5 mRNAs using a GeneXpert instrument. The primary aim of this review was to systematically review and pool the data regarding the diagnostic performance of Xpert BC in patients with NMIBC. METHODS: Systematic literature search using 4 electronic databases (PubMed, EMbase, Scopus and Web of science) was performed. Pooled sensitivity, specificity and diagnostic odds ratio (DOR) were estimated using DerSimonian-Laird random-effects model. Standard Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed and the study protocol was registered with PROSPERO (CRD42021249762). RESULTS: In this review, 11 prospective studies with 2,896 patients were included. Pooled sensitivity and specificity for Xpert BC were 73% (95% confidence interval (CI) 65%-80%) and 77% (95% CI 69%-84%) respectively. Area under curve (AUC) for Xpert BC monitor was 0.81 (0.78-0.84) respectively. Subgroup analysis from 7 studies for patients with high-grade recurrence revealed sensitivity, specificity and AUC of 0.86 (0.77-0.92), 0.78 (0.75-0.81) and 0.87 (0.84-0.90) respectively. Similar analysis for patients with low-grade recurrence revealed sensitivity, specificity and AUC of 0.58 (0.47-0.68), 0.79 (0.75-0.82) and 0.79 (0.75-0.82) respectively. CONCLUSION: Xpert BC monitor has overall acceptable diagnostic accuracy. Sensitivity is higher for high-grade disease for detecting recurrences in patients with NMIBC on surveillance.

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.

Spontaneous Erosion of Retained Bone Chip into Anal Canal Following Progressive Perineal Urethroplasty with Inferior Pubectomy: Lessons Learnt!

We present a never before reported delayed complication of progressive perineal urethroplasty with inferior pubectomy in a young male, where retained bone chip spontaneously erodes through anal canal. Our case cautions urologists doing inferior pubectomy for pelvic fracture urethral distraction defect to make sure that no loose bony fragment is left in the operative field. We also emphasize to make sure to nibble the sharp bony margins of the cut pubic bone after inferior pubectomy so that it will not impinge onto the anterior wall of rectum eliminating the risk of delayed perforation of rectum or anal canal.