Primary Retroperitoneal Lymph Node Dissection for Seminoma Metastatic to the Retroperitoneum.

PURPOSE: Primary surgical treatment with retroperitoneal lymph node dissection aims to accurately stage and treat patients with node-positive pure seminoma while avoiding long-term risks of chemotherapy or radiation, traditional standard-of-care treatments. MATERIALS AND METHODS: We reported the pathologic and oncologic outcomes of patients with pure seminoma treated with primary retroperitoneal lymph node dissection in a retrospective, single-institution case series over 10 years. The primary outcome was 2-year recurrence-free survival stratified by adjuvant management strategy (surveillance vs adjuvant chemotherapy). RESULTS: Forty-five patients treated with primary retroperitoneal lymph node dissection for pure testicular seminoma metastatic to the retroperitoneum were identified. Median size of largest lymph node before surgery was 1.8 cm. Viable germ cell tumor, all of which was pure seminoma, was found in 96% (n=43) of patients. The median number of positive nodes and nodes removed was 2 and 54, respectively. Median positive pathologic node size was 2 cm (IQR 1.4-2.5 cm, range 0.1-5 cm). Four of 29 patients managed with postoperative surveillance experienced relapse; 2-year recurrence-free survival was 81%. Median follow-up for those managed with surveillance who did not relapse was 18.5 months. There were no relapses in the retroperitoneum, visceral recurrences, or deaths. Among the 16 patients who received adjuvant treatment, 1 patient experienced relapse in the pelvis at 19 months. CONCLUSIONS: Primary retroperitoneal lymph node dissection for pure seminoma with low-volume metastases to the retroperitoneum is safe and effective, allowing most patients to avoid long-term toxicities from chemotherapy or radiation.

Do Phosphodiesterase Type 5 Inhibitors Increase the Risk of Biochemical Recurrence After Radical Prostatectomy?

PURPOSE: There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP. MATERIALS AND METHODS: An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models. RESULTS: The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR. CONCLUSIONS: Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.

Analysis of diurnal variation in serum testosterone levels in men with symptoms of testosterone deficiency.

BACKGROUND: Testosterone (T) plays a crucial role in various physiological functions in men, and understanding the variations in T levels during the day is essential for diagnosing and treating testosterone deficiency (TD). AIM: We sought to evaluate the reduction in serum total T (TT) levels throughout the day in men with symptoms of testosterone deficiency and to determine the variables having an impact on the extent of this decline. METHODS: The study population consisted of a group of men who within 3 months of each other had all undergone both early morning and afternoon TT level measurements. We did not include patients with a history of a prior orchiectomy, testosterone levels below 100 ng/dL or above 1000 ng/dL, a history of androgen deprivation therapy, or patients on T therapy. Statistical analyses were conducted using descriptive statistics, t-tests, chi-square tests, and correlation calculations. Liquid chromatography-tandem mass spectrometry was used to measure TT, and a change in TT levels greater than 100 ng/dL was considered significant. Using multivariable and univariable analysis, we attempted to define predictors of a decrease in afternoon TT levels. OUTCOMES: The majority of men showed no significant difference in T levels between morning and afternoon. RESULTS: In total, 506 men with a median age of 65 years were analyzed. The most common comorbidities were hypertension and hyperlipidemia. Levels of TT were measured in the morning and afternoon, and no significant differences in mean T levels based on the time of the test were found. Age was not significantly associated with T levels. CLINICAL IMPLICATIONS: There was a weak negative correlation between age and the difference between morning and afternoon T levels, with younger men showing more significant variations in T levels. The most considerable differences in T levels were observed in men younger than 30 years. There were no predictors of the magnitude of the T decrease in the afternoon. STRENGTHS AND LIMITATIONS: Strengths of the study include the number of subjects and the use of liquid chromatography-tandem mass spectrometry for T measurement. Limitations include failure to measure morning and afternoon T levels on the same day, the retrospective nature of the study, and a smaller sample size of patients younger than 30 years. CONCLUSION: In this study we found no strong link between age and daily T fluctuation, but we observed a decrease in the magnitude of variation with aging. The group experiencing the most significant decline in daily T had higher morning and consistently normal afternoon T levels.

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Predictive value of kallikrein forms and ß-microseminoprotein in blood from patients with evidence of detectable levels of PSA after radical prostatectomy.

PURPOSE: To determine whether ß-microseminoprotein or any of the kallikrein forms in blood-free, total or intact PSA or total hK2-predict metastasis in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. METHOD: We determined marker concentrations in blood from 173 men treated with radical prostatectomy and evidence of detectable levels of PSA in the blood (PSA ≥ 0.05) after surgery between 2014 and 2015 and at least 1 year after any adjuvant therapy. We used Cox regression to determine whether any marker was associated with metastasis using both univariate and multivariable models that included standard clinical predictors. RESULTS: Overall, 42 patients had metastasis, with a median follow-up of 67 months among patients without an event. The levels of intact and free PSA and free-to-total PSA ratio were significantly associated with metastasis. Discrimination was highest for free PSA (c-index: 0.645) and free-to-total PSA ratio (0.625). Only free-to-total PSA ratio remained associated with overall metastasis (either regional or distant) after including standard clinical predictors (p = 0.025) and increased discrimination from 0.686 to 0.697. Similar results were found using distant metastasis as an outcome (p = 0.011; c-index increased from 0.658 to 0.723). CONCLUSION: Our results provide evidence that free-to-total PSA ratio can risk stratifying patients with evidence of detectable levels of PSA in blood after RP. Further research is warranted on the biology of prostate cancer markers in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Our findings on the free-to-total ratio for predicting adverse oncologic outcomes need to be validated in other cohorts.

Reducing opioid prescribing after ambulatory breast reconstruction surgery.

BACKGROUND: The lack of evidence-based guidelines for postoperative opioid prescriptions following breast reconstruction contributes to a wide variation in prescribing practices and increases potential for misuse and abuse. METHODS: Between August and December 2019, women who underwent outpatient breast reconstruction were surveyed 7-10 days before (n = 97) and after (n = 101) implementing a standardized opioid prescription reduction initiative. We compared postoperative opioid use, pain control, and refills in both groups. Patient reported outcomes were compared using the BREAST-Q physical wellbeing of the chest domain and a novel symptom Recovery Tracker. RESULTS: Before changes in prescriptions, patients were prescribed a median of 30 pills and consumed three pills (interquartile range [IQR: 1,9]). After standardization, patients were prescribed eight pills and consumed three pills (IQR: 1,6). There was no evidence of a difference in the proportion of patients experiencing moderate to very severe pain on the Recovery Tracker or in the early BREAST-Q physical wellbeing of the chest scores (p = 0.8 and 0.3, respectively). CONCLUSION: Standardizing and reducing opioid prescriptions for patients undergoing reconstructive breast surgery is feasible and can significantly decrease the number of excess pills prescribed. The was no adverse impact on early physical wellbeing, although larger studies are needed to obtain further data.

Papillary renal cell carcinoma: a single institutional study of 199 cases addressing classification, clinicopathologic and molecular features, and treatment outcome.

The morphologic spectrum of type 1 papillary renal cell carcinoma (PRCC) is not well-defined, since a significant proportion of cases have mixed type 1 and 2 histology. We analyzed 199 cases of PRCC with any (even if focal) type 1 features, with a median follow-up of 12 years, to identify clinicopathological features associated with outcome. Ninety-five tumors (48%) of the cohort contained some type 2 component (median amount: 25%; IQR: 10%, 70%). As a group they showed high rates of progression-free (PFS) and cancer-specific survival (CSS). Tumor size, mitotic rate, lymphovascular invasion, sarcomatoid differentiation, sheet-like architecture, and lack of tumor circumscription were significantly associated with CSS (p ≤ 0.015) on univariate analysis. While predominant WHO/ISUP nucleolar grade was associated with PFS (p = 0.013) and CSS (p = 0.030), the presence of non-predominant (<50%) nucleolar grade did not show association with outcome (p = 0.7). PFS and CSS showed no significant association with the presence or the amount of type 2 morphology. We compared the molecular alterations in paired type 1 and type 2 areas in a subset of 22 cases with mixed type 1 and 2 features and identified 12 recurrently mutated genes including TERT, ARID1A, KDM6A, KMT2D, NFE2L2, MET, APC, and TP53. Among 78 detected somatic mutations, 61 (78%) were shared between the paired type 1 and type 2 areas. Copy number alterations, including chromosome 7 and 17 gains, were similar between type 1 and 2 areas. These findings support that type 2 features in a PRCC with mixed histology represent either morphologic variance or clonal evolution. Our study underscores the notion that PRCC with any classic type 1 regions is best considered as type 1 PRCC and assigned the appropriate WHO/ISUP nucleolar grade. It provides additional evidence that type 2 PRCC as a separate category should be re-assessed and likely needs to be abandoned.

Prevalence of High-Risk Prostate Cancer Metastasis to Cloquet's Ilioinguinal Lymph Node.

PURPOSE: Cloquet's node, located at the junction between the deep inguinal nodes and the external iliac chain, is easily accessible and commonly excised during pelvic lymph node dissection for prostate cancer. However, we hypothesize that Cloquet's node is not part of lymphatic metastatic spread of prostate cancer. MATERIALS AND METHODS: Between September 2016 and June 2019, 105 consecutive patients with high-risk prostate cancer (cT3a or Grade Group 4/5, or prostate specific antigen >20 ng/ml) underwent a laparoscopic radical prostatectomy and pelvic lymph node dissection. First, Cloquet's node was identified, retrieved and submitted separately to pathology as right and left Cloquet's node. Next, a pelvic lymph node dissection was completed including the external iliac, obturator fossa and hypogastric nodal packets. Each lymph node was cut into 3 mm slices which were separately embedded in paraffin, stained with hematoxylin and eosin, and examined microscopically. RESULTS: The final analysis included 95 patients. In this high-risk population, the median number of nodes removed was 22 (IQR 18-29); 39/95 patients (41%) had lymph node metastasis. The median number of Cloquet's nodes removed was 2 (IQR 2-3). Cloquet's node was negative in all but 1 patient (1.1%), who had very high-risk features and high metastatic burden in the lymph nodes. CONCLUSIONS: In high-risk prostate cancer, metastasis to the ilioinguinal node of Cloquet is rare. Given this low prevalence, Cloquet's node can be safely excluded from the pelvic lymph node dissection template.

Oncologic Outcomes of Total Length Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer.

PURPOSE: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. MATERIALS AND METHODS: We compared 4 GP4 quantification methods-including maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume core-for prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. RESULTS: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81-88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrence-maximum %GP4 (HR=1.30; 95% CI 1.07-1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21-2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36-4.52; p=0.003) and length GP4 in highest core (HR=1.32; 95% CI 1.11-1.57; p=0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. CONCLUSIONS: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.

Association of Biochemically Verified Post-Diagnosis Smoking and Nonmuscle-Invasive Bladder Cancer Recurrence Risk.

PURPOSE: Our goal was to determine the association between biochemically verified post-diagnosis smoking exposure and nonmuscle-invasive bladder cancer (NMIBC) recurrence risk. MATERIALS AND METHODS: We conducted a prospective study of 354 NMIBC patients with a smoking history undergoing care between 2015 and 2018. Patients contributed at least 2 biospecimens during followup which were tested for cotinine to determine biochemically verified post-diagnosis smoking exposure (yes/no). Our primary endpoint was time to first recurrence after study start date. We examined whether post-diagnosis smoking exposure was associated with recurrence risk in multivariable Cox proportional hazards models that accounted for demographics, clinicopathological variables, time since diagnosis and pack-years. RESULTS: Patients were predominantly White, male and had a median age of 68 years. Most patients had Ta disease (62%) and tumors of high grade (68%). Intravesical bacillus Calmette-Guérin was given to 63% of the cohort. Patients were followed for a median of 3.6 years since study start. Post-diagnosis smoking exposure was detected in 22% of patients, and 38.7% (137) of patients experienced a recurrence during followup. In multivariable models, only bacillus Calmette-Guérin treatment and prior recurrence rate were significantly associated with recurrence. There was no association between post-diagnosis smoking exposure and recurrence risk (HR: 0.73, 95% CI: 0.45-1.20). CONCLUSIONS: In a cohort of patients with predominantly high risk NMIBC, post-diagnosis smoking exposure was not associated with NMIBC recurrence. However, smoking cessation support remains a critical component of cancer care given that the benefits of quitting extend far beyond NMIBC recurrence.

Uretero-enteric stricture outcomes: secondary analysis of a randomised controlled trial comparing open versus robot-assisted radical cystectomy.

OBJECTIVES: To analyse the risk of uretero-enteric anastomotic stricture in patients randomised to open (ORC) or robot-assisted radical cystectomy (RARC) with extracorporeal urinary diversion. PATIENTS AND METHODS: We included 118 patients randomised to RARC (n = 60) or ORC (n = 58) at a single, high-volume institution from March 2010 to April 2013. Urinary diversion was performed by experienced open surgeons. Stricture was defined as non-malignant obstruction on imaging, corroborated by clinical status, and requiring procedural intervention. The risk of stricture within 1 year was compared between groups using Fisher's exact test. RESULTS: In all, 58 and 60 patients were randomised to RARC and ORC, respectively. We identified five strictures, all in the ORC group. In patients with ≥1 year of follow-up, the increase in risk of stricture from open surgery was 9.3% (95% confidence interval 1.5%, 17%). Of the five strictures, three were managed endoscopically while two required open revision. There was no evidence that perioperative Grade 3-5 complications were associated with development of a stricture (P = 1) and no evidence of a difference in 24-month estimated glomerular filtration rate between arms (P = 0.15). CONCLUSIONS: In this study at a high-volume centre, RARC with extracorporeal urinary diversion achieved excellent ureteric anastomotic outcomes. Purported increased risk of stricture is not a reason to avoid RARC. Future research should examine the impact of different surgical techniques and operator experience on the risk of stricture, especially as more intracorporeal diversions are performed.

The association between modifiable perioperative parameters and renal function after nephrectomy.

OBJECTIVE: To evaluate the association between intraoperative anaesthetic parameters, primarily intraoperative hypotension, and postoperative renal function in patients undergoing nephrectomy. PATIENTS AND METHODS: We reviewed data from 3240 consecutive patients who underwent nephrectomy between 2010 and 2018. Anaesthetic parameters evaluated included duration of hypotension, tachycardia, hypothermia, volatile anaesthetic use and mean arterial pressure in the post-anaesthesia care unit. Outcomes included acute kidney injury (AKI) and estimated glomerular filtration rate (eGFR) within the first year after nephrectomy. Associations between anaesthetic parameters and outcomes were evaluated with multivariable logistic regression and generalised estimating equation, respectively, adjusted for predictors of renal function after nephrectomy. RESULTS: Before nephrectomy, 677 (21%) patients had moderate-severe chronic kidney disease. A quarter of patients (n = 809) had postoperative AKI and 35% (n = 746) had Stage ≥3 chronic kidney disease 12-months after surgery. Only 12% of patients (n = 386) had >5 min of intraoperative hypotension. While not statistically significant, longer duration of intraoperative hypotension was associated with slightly higher rates of AKI (odds ratio [OR] per 10-min 1.14, 95% confidence interval [CI] 0.98, 1.32). Prolonged hypothermia was associated with increased rate of AKI (OR per 10-min 1.02, 95% CI 1.00, 1.04), and decreased eGFR (change in eGFR per 10-min -0.19, 95% CI -0.27, -0.12); however, these results have limited clinical significance. CONCLUSIONS: Under current practice, intraoperative anaesthetic parameters are tightly maintained, restricting the significance of their effect on postoperative renal function. Future studies should evaluate whether haemodynamic parameters during the early postoperative period, when they are monitored less frequently, are associated with renal functional outcome.

The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer.

BACKGROUND: Prostate-specific antigen (PSA) secretion is a testosterone (T) dependent process. Published data suggest that a low T level is an independent predictor of higher-grade prostate cancer (PC). AIM: To evaluate the relationship between T and PSA in patients with PC. METHODS: All men diagnosed with PC with a recorded pre-treatment total T level measurement were included in this analysis. We analyzed demographic, clinical, and pathological data. Patients were stratified according to pretreatment PSA levels: <2 ng/mL, 2-4 ng/mL, >4 ng/mL. Low T was defined as total T < 10.4 nmol/L (300 ng/dL), very low T < 6.9 nmol/L (200 ng/dL). OUTCOMES: T levels by PSA groups according to the PC pathology. RESULTS: In this retrospective study, mean patient age was 61 years among 646 men. The distribution by PSA group was: 8% (<2), 17% (2-4), and 76% (>4). The mean T level across the entire cohort was 13 nmol/L (374 ng/dL). Overall, 30% had a T level < 10.4 nmol/L (300 ng/dL). The mean total T level by PSA group was: <2 ng/mL, 7 nmol/L (206 ng/dL); 2-4 ng/mL, 13 nmol/L (362 ng/dL); >4 ng/mL, 14 nmol/L (393 ng/dL), P < .001. PSA <4 ng/mL was a significant predictor of low T in men with PC GS ≥8. PSA <2 ng/mL was a significant predictor of very low T independent of the PC pathology. CLINICAL IMPLICATIONS: These findings suggest that clinicians should consider measuring T levels when a patient diagnosed with PC GS ≥8 and PSA level <4 ng/mL, and for each patient with PSA level <2 ng/mL independent of the PC pathology. STRENGTHS & LIMITATIONS: Our study has several strengths including (i) inclusion of a large population of men, (ii) use of a database which is audited and reviewed for accuracy annually, and (iii) use of an accurate T assay (LCMS). Nonetheless, there are limitations: (i) the subjects of the study are from a single institution, and (ii) we did not measure free T levels. CONCLUSION: In men with PC with GS ≥8, PSA level <4 ng/mL predicts low T. PSA <2 ng/mL predicts very low T independent of the PC pathology. Flores JM, Bernie HL, Miranda E, et al. The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer. J Sex Med 2022;19:471-478.

Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy.

BACKGROUND: Prior studies suggest that men with good erectile function shortly after radical prostatectomy (RP) can subsequently have worsened erectile function. AIM: To determine the prevalence and predictors of early erectile function recovery post-RP and of worsening erectile function after initial erectile function recovery. METHODS: We retrospectively queried our institutional database. Men who underwent RP during 2008-2017 and who completed the International Index of Erectile Function erectile function domain both pre-RP and serially post-RP, constituted the population. Functional erections were defined as International Index of Erectile Function (IIEF)-6 erectile function domain scores ≥24. We analyzed factors predicting functional erections at 3 months post-RP as well as factors predicting a decrease in functional erections between 3 and 6 months, defined as ≥2-point drop in the erectile function domain. Multivariable logistic regression models were used to identify predictors of early erectile function recovery and also of subsequent decline. OUTCOMES: Erectile function recovery rates at 3 months post-RP and predictive factors; rates of erectile function decline between 3-6 months and associated predictors. RESULTS: Eligible patients comprised 1,655 men with median age of 62 (IQR 57, 67) years. Bilateral nerve-sparing (NS) surgery was performed in 71% of men, unilateral NS in 19%, and no NS in 10%. Of this population, 224 men (14%; 95% CI 12%, 15%) had functional erections at 3 months post-RP. On multivariable analysis, significant predictors of early erectile function recovery included: younger age (OR 0.93, P < .001), higher baseline erectile function domain score (OR 1.14, P < .001) and bilateral NS (OR 3.81, P = .002). The presence of diabetes (OR 0.43, P = .028) and a former smoking history (OR 0.63, P = .008; reference group: never smoker) was associated with the erectile dysfunction at 3 months post-RP. Of the men with early functional erections, 41% (95% CI 33%, 48%) had a ≥ 2-point decline in erectile function between 3 and 6 months. No factors were identified as predictors for this decline. CLINICAL IMPLICATIONS: Only a small proportion of men have functional erections at 3 months post-RP and a notable number of them will experience a decline in erectile function between 3 and 6 months. STRENGTHS AND LIMITATIONS: Strengths: large patient population and the use of validated questionnaire. LIMITATIONS: single-center retrospective study. CONCLUSION: A minority of men had functional erections 3 months post-RP, about half of whom had a decline in erectile function by month 6. We recommend appropriately counseling post-RP patients on the risk of such a decline in erectile function. Salter CA, Tin AL, Bernie HL, et al. Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy. J Sex Med 2022;19:1790-1796.

Luteinizing Hormone Suppression Profiles in Men Treated With Exogenous Testosterone.

BACKGROUND: Due to the negative feedback mechanism involved in the hypothalamic-pituitary-gonadal axis, testosterone therapy (TTh) may result in suppression of luteinizing hormone (LH) secretion, but clinical experience demonstrates the level of LH suppression is variable. AIM: We sought to define the relationship between TTh and LH levels, specifically predictors of LH suppression in men on TTh. METHODS: We performed a retrospective analysis of a prospectively maintained database of patients with testosterone deficiency (TD) treated with TTh. Patient demographic and clinical data including vascular risk factor (VRF) status were collected. Serum total T and LH levels before TTh and after ≥3 months (m) were recorded. LH suppression was defined as serum LH level <1.0 IU/ml. MAIN OUTCOME MEASURES: Predictors of LH suppression were searched though a series of logistic regression models assessing suppression status at the final observation, and then a series of Cox proportional hazards models assessing time to first suppression were performed. RESULTS: A total of 227 patients with mean age of 58±14 years at time of TTh initiation were included in our analysis. Just under half of subjects received transdermal T as the only modality (n = 101, 44%), while one third (n = 77, 34%) received intramuscular only, and the remainder (n = 49, 22%) received both modalities during follow-up. The mean baseline LH level was 10 ± 12 IU/ml. The percent of men who had baseline LH level above 1 IU/ml and at any given point of TTh was 84% and 78%, respectively, thus 22% of men had suppressed LH levels on TTh considering the definition of LH <1 IU/ml. Most men (73%) had a suppressed LH level of <1 IU/ml at least once during follow-up. In the final adjusted model for LH suppression, intramuscular route (OR = 2.44), baseline LH (OR = 0.94), estradiol (OR = 1.05) remained significant. CLINICAL IMPLICATIONS: LH suppression profiles may be relevant for dose titration during TTh and perhaps to minimize testicular atrophy. STRENGTHS & LIMITATIONS: A strict definition for TD was applied using LCMS for T measurements and patients had long-term follow-up. CONCLUSION: While 73% of patients had at least one LH <1 IU/ml during TTh, only 22% maintained suppressed throughout the treatment. Miranda EP, Schofield E, Matsushita K, et al. Luteinizing Hormone Suppression Profiles in Men Treated With Exogenous Testosterone. J Sex Med 2022;19:1359-1365.

Morbidity of salvage radical prostatectomy: limited impact of the minimally invasive approach.

PURPOSE: We aimed to report the morbidity profile of salvage radical prostatectomy (SRP) after radiotherapy failure and assess the impact of minimally invasive surgery (MIS) on postoperative complications and functional outcomes. MATERIALS AND METHODS: Between 1985 and 2019, a total of 293 patients underwent SRP; 232 underwent open SRP; and 61 underwent laparoscopic SRP with or without robotic assistance. Complications were recorded and classified into standardized categories per the Clavien-Dindo classification. RESULTS: Twenty-nine patients (10%) experienced grade 3 complications within 30 days, 22 (9.5%) after open and 7 (11%) after MIS (p = 0.6). Between 30 and 90 days after surgery, 7.3% of patients in the open group and 10% in the MIS group had grade 3 complications (p = 0.5). The most common complication was bladder neck contracture (BNC), representing 40% of the 30-90 day complications. Within one year of SRP, 81 patients (31%, 95% CI 25%, 37%) developed BNC; we saw non-significant lower rates in MIS (25 vs 32%; p = 0.4). Functional outcomes were poor after SRP and showed no difference between open and MIS groups for urinary continence (16 vs 18%, p = 0.7) and erectile function (7 vs 13%, p = 0.4). 5 year cancer-specific survival and overall survival was 95% and 88% for the entire cohort, respectively. CONCLUSIONS: Our outcomes suggest poor functional recovery after SRP, regardless of the operative approach. Currently there is no evidence favoring the use of open or MIS approach. Further studies are required to ensure comparable outcomes between these approaches.

Electronic Rapid Fitness Assessment Identifies Factors Associated with Adverse Early Postoperative Outcomes following Radical Cystectomy.

PURPOSE: Frailty is associated with adverse outcomes following radical cystectomy. Prospective tools to identify factors affecting outcomes are needed. We describe a novel electronic rapid fitness assessment to evaluate geriatric patients undergoing radical cystectomy. MATERIALS AND METHODS: Before undergoing radical cystectomy between February 2015 and February 2018, 80 patients older than age 75 years completed the electronic rapid fitness assessment and were perioperatively comanaged by the Geriatrics Service. Physical function and cognitive function over 12 domains were evaluated and an accumulated geriatric deficit score was compiled. Hospital length of stay, discharge disposition, unplanned intensive care unit admissions, urgent care visits, readmissions, complications and deaths were assessed. RESULTS: A total of 65 patients who underwent radical cystectomy for bladder cancer without concomitant procedures completed the assessment. Median age was 80 (77, 84) years and 52 (80%) were male. A higher proportion of patients with intensive care unit admission, urgent care visit and major complications had impairments identified within electronic rapid fitness assessment domains, including Timed Up and Go. Readmission rates were similar between patients with or without deficits identified. Higher accumulated geriatric deficit score was significantly associated with intensive care unit admission (p=0.035), death within 90 days (p=0.037) and discharge to other than home (p=0.0002). CONCLUSIONS: We demonstrated the feasibility of assessing fitness in patients older than 75 years undergoing radical cystectomy using a novel electronic fitness tool. Physical limitations and overall impairment corresponded to higher intensive care unit admission rates and adverse postoperative outcomes. Larger studies in less resourced environments are required to validate these findings.

Examining the Accuracy of Self-Reported Smoking-Related Exposure among Recently Diagnosed Nonmuscle Invasive Bladder Cancer Patients.

PURPOSE: Cigarette smoking is a risk factor for developing nonmuscle invasive bladder cancer, and continued smoking exposure after diagnosis may increase the likelihood of adverse clinical outcomes. We compare self-reported vs biochemically verified nicotine exposure to determine the accuracy of self-report among recently diagnosed nonmuscle invasive bladder cancer patients. MATERIALS AND METHODS: This cross-sectional analysis consisted of 517 nonmuscle invasive bladder cancer patients who contributed a urine or saliva specimen the same day as self-reporting their smoking, use of e-cigarettes, nicotine replacement therapy and whether they lived with a smoker. Cotinine, the primary metabolite of nicotine, was used as an objective biomarker of recent nicotine exposure. RESULTS: The prevalence of high, low and no cotinine exposure was 13%, 54% and 33%, respectively. Overall, 7.3% of patients (38/517) reported being a current cigarette smoker, while 13% (65/517) had cotinine levels consistent with active smoking exposure. Of these 65 patients 27 denied current smoking, resulting in a sensitivity of self-reported current smoking of 58%. After considering other sources of nicotine exposure such as e-cigarettes, cigars, nicotine replacement therapy and living with a smoker, the sensitivity was higher, at 82%. Nearly all patients with low cotinine denied any smoking-related exposure. CONCLUSIONS: Our findings suggest either biochemical verification with cotinine or additional questions about other sources of nicotine are needed to accurately identify nonmuscle invasive bladder cancer patients who have smoking-related exposures. Accurate classification of active and passive smoking exposure is essential to allow clinicians to advise cessation and help researchers estimate the association between post-diagnosis smoking-related exposure and nonmuscle invasive bladder cancer recurrence risk.

A Randomized, Controlled, 3-Arm Trial of Pharmacological Penile Rehabilitation in the Preservation of Erectile Function After Radical Prostatectomy.

BACKGROUND: Although the concept of penile rehabilitation after radical prostatectomy (RP) has been advocated for decades, there is little definitive evidence regarding its utility or the best strategy to optimize patient outcomes. AIM: The goal of this study is to analyze the ability of 3 different pharmacological strategies to preserve the ability of men to achieve spontaneous (non-medication assisted) erections after bilateral nerve-sparing RP. METHODS: This IRB- and FDA-approved study studied penile rehabilitation in a 3-arm fashion with a target enrollment of 200 patients. (i) Control arm: nightly placebo with sildenafil 100 mg on demand for sexual relations (up to 6 pills/month); (ii) nightly sildenafil arm: nightly sildenafil 50 mg and sildenafil 100 mg on demand for sexual relations (up to 6 pills/month); (iii) combination therapy arm: nightly sildenafil 50 mg (5 nights/week) plus intracavernosal injections twice/week. Inclusion criteria included bilateral nerve-sparing surgery, normal serum total testosterone, and good preoperative baseline erectile function as measured by the erectile function domain score of the IIEF (EFD) (≥24). Patients were followed with a medication use diary and the IIEF questionnaire at 6 weeks, 3 m, 6 m, 12 m, 18 m and 24 m. OUTCOMES: A difference was seen in the IIEF-EFD scores between the 3 groups at 24 months after RP. Secondary end points include the time to return of spontaneous functional erections, the time for patients to respond to oral erectogenic therapy, and the proportion of patients who have normalization of their IIEF-EFD scores. RESULTS: The study was interrupted because of failure to recruit the target study population in a reasonable timeframe. A total of 76 subjects with median age of 57 (IQR: 51, 63) years and mean IIEF-EFD of 29 (IQR: 27, 30) were initially randomized, but at 24 months, the sample sizes by group were (i) n = 4; (ii) n = 18; and (iii) n = 10, with median IIEF-EFD 24 (IQR: 18, 28), 24 (IQR: 18, 28), and 21 (IQR: 9, 26), respectively. There was no statistical difference among the groups in the final analysis. CLINICAL IMPLICATIONS: Definitive evidence for the ability of different pharmacological rehabilitation strategies to improve long-term EF outcomes might never be available. STRENGTHS & LIMITATIONS: This was a well-designed randomized and 3-arm designed trial intended to provide decisive evidence regarding the utility of penile rehabilitation. Failure to recruit the target population is the main limitation. CONCLUSION: The limited number of patients in the present trial precludes definitive interpretation. However, results indicate how challenging it is to conduct true rehabilitation studies. Miranda EP, Benfante N, Kunzel B, et al. A Randomized, Controlled, 3-Arm Trial of Pharmacological Penile Rehabilitation in the Preservation of Erectile Function After Radical Prostatectomy. J Sex Med 2021;18:423-429.

Development and Validation of the Satisfaction Survey for Inflatable Penile Implant (SSIPI).

BACKGROUND: No validated English language patient-reported outcome (PRO) currently exists that assesses satisfaction with inflatable penile prosthesis (IPP). Satisfaction data have been largely based primarily on surgeon assessment of patients or using questionnaires that have not been designed for this purpose. AIM: To develop an English-language validated PRO that assesses patient satisfaction after IPP surgery. METHODS: Initially, a literature review and discussions with experts defined domains important to IPP satisfaction (pain, appearance, function, overall satisfaction). The initial 35-item Satisfaction Survey for Inflatable Penile Implant (SSIPI) was developed. Cognitive interviews were then performed with IPP patients (n = 12) to gain feedback on the SSIPI domains and items. These data were used to modify SSIPI with the addition of 2 questions for a final item number of 37. Patients from 4 centers, who were between 6 months and 5 years after IPP, were administered the questionnaire through RedCap. Reliability statistics and content analysis were used to winnow questions to yield the final 16-item version of the SSIPI. Internal consistency was assessed via Cronbach's alpha and item-total correlation. Test-retest reliability was assessed via intraclass correlation coefficients using baseline and 2-week data. For convergent validity, the Erectile Dysfunction Inventory of Treatment Satisfaction and the Self-Esteem and Relationship (SEAR) questionnaire were used. For discriminant validity, the International Prostate Symptom Score (IPSS) was used. Confirmatory factor analysis was used to assess the factor structure of the SSIPI. OUTCOMES: Internal consistency, test-retest reliability, convergent and discriminant validity, and confirmatory factor analysis were assessed. RESULTS: 118 men were surveyed. Mean age was 66.8 ± 9.5 years. The 16-item SSIPI showed high internal consistency with an overall Cronbach's Alpha of 0.97 (domains 0.85-0.89). Item-total correlations for individual items to subscales ranged from 0.60 to 0.91. The overall test-retest reliability was 0.94 (domains 0.87-0.93). Erectile Dysfunction Inventory of Treatment Satisfaction and Self-Esteem and Relationship had correlations of 0.84 overall (domains 0.57-0.79) and 0.47 overall (domains 0.34-0.44), respectively. International Prostate Symptom Score (discriminant validity) had correlations of -0.29 overall (domains -0.17 to -0.31). CLINICAL IMPLICATIONS: SSIPI is the first English-language validated IPP satisfaction PRO. This will enable clinicians to collect satisfaction data in a standardized way. STRENGTHS AND LIMITATIONS: As strengths we have used a rigorous psychometric process and have no industry sponsorship. Limitations include small numbers of specific subpopulations. CONCLUSION: The SSIPI has demonstrated robust psychometric properties. Salter CA, Bach PV, Jenkins L, et al. Development and Validation of the Satisfaction Survey for Inflatable Penile Implant (SSIPI). J Sex Med 2021;18:1641-1651.