Evaluating residual tumor after neoadjuvant chemotherapy for muscle-invasive urothelial bladder cancer: diagnostic performance and outcomes using biparametric vs. multiparametric MRI

BACKGROUND Neoadjuvant chemotherapy (NAC) before radical cystectomy is standard of care in patients with muscle-invasive bladder cancer (MIBC). Response assessment after NAC is important but suboptimal using CT. We assessed MRI without vs. with intravenous contrast (biparametric [BP] vs. multiparametric [MP]) for identifying residual disease on cystectomy and explored its prognostic role. METHODS Consecutive MIBC patients that underwent NAC, MRI, and cystectomy between January 2000-November 2022 were identified. Two radiologists reviewed BP-MRI (T2 + DWI) and MP-MRI (T2 + DWI + DCE) for residual tumor. Diagnostic performances were compared using receiver operating characteristic curve analysis. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with disease-free survival (DFS). RESULTS 61 patients (36 men and 25 women; median age 65 years, interquartile range 59-72) were included. After NAC, no residual disease was detected on pathology in 19 (31.1%) patients. BP-MRI was more accurate than MP-MRI for detecting residual disease after NAC: area under the curve = 0.75 (95% confidence interval (CI), 0.62-0.85) vs. 0.58 (95% CI, 0.45-0.70; p = 0.043). Sensitivity were identical (65.1%; 95% CI, 49.1-79.0) but specificity was higher in BP-MRI compared with MP-MRI for determining residual disease: 77.8% (95% CI, 52.4-93.6) vs. 38.9% (95% CI, 17.3-64.3), respectively. Positive BP-MRI and residual disease on pathology were both associated with worse DFS: hazard ratio (HR) = 4.01 (95% CI, 1.70-9.46; p = 0.002) and HR = 5.13 (95% CI, 2.66-17.13; p = 0.008), respectively. Concordance between MRI and pathology results was significantly associated with DFS. Concordant positive (MRI+/pathology+) patients showed worse DFS than concordant negative (MRI-/pathology-) patients (HR = 8.75, 95% CI, 2.02-37.82; p = 0.004) and compared to the discordant group (MRI+/pathology- or MRI-/pathology+) with HR = 3.48 (95% CI, 1.39-8.71; p = 0.014). CONCLUSION BP-MRI was more accurate than MP-MRI for identifying residual disease after NAC. A negative BP-MRI was associated with better outcomes, providing complementary information to pathological assessment of cystectomy specimens

Multiple partial nephrectomy for multifocal synchronous renal cancer in a solitary kidney

Introduction & Objectives: multifocal synchronous renal cancer on a solitary kidney represent a challenging clinical scenario. The complexity of imperative nephron-sparring surgery in this setting resides in ensuring complete excision of cancer with the maximal preservation of renal function. We aim to present a case of multiple partial nephrectomy (MPN) for multifocal synchronous renal cancer in a patient with a solitary kidney and discuss our experience of imperative partial in this setting. Materials & Methods: We present a case of a 76 years old man with a past medical history of hypertension, chronic obstructive pulmonary disease, peripheral vascular disease, left radical nephrectomy for renal mass (2006) and a right renal artery stent placement for renal artery stenosis. During his surveillance, computerized axial tomography (CAT) scan showed 3 enhancing renal masses (2.2cm, 1.5cm and 1cm, respectively). Biopsy of the largest mass was consistent in clear cell renal cell carcinoma (ccRCC). Preoperative level of creatinine was 1.4mg/dL and estimated glomerular filtration rate (eGFR) 50ml/min/1,73m2. After ablative therapy was deemed unsafe, a MPN was planned

Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically

PURPOSE: To assess the association between obstructive sleep apnea (OSA) and Fuhrman grade in patients with clear cell renal cell carcinoma (ccRCC). As secondary endpoints, we studied its association with tumor size, metastasis-free survival (MFS) and cancer-specific survival (CSS). METHODS: We reviewed the databases of two tertiary care centers, identifying 2579 patients who underwent partial or radical nephrectomy for ccRCC between 1991 and 2014. Descriptive statistics were used to compare pathologic variables between patients with and without OSA. Linear and logistic regression models were used to assess the association of OSA with Fuhrman grade and tumor size. A Cox proportional hazards model was used to determine OSA association with MFS and CSS. A pathway analysis was performed on a cohort with available gene expression data. RESULTS: In total, 172 patients (7 %) had self-reported OSA at diagnosis. More patients with OSA had high Fuhrman grade compared to those without OSA [51 vs. 38 %; 13 % risk difference; 95 % confidence interval (CI), 5-20 %; p = 0.003]. On multivariable analysis, the association remained significant (OR 1.41; 95 % CI 1.00-1.99; p = 0.048). OSA was not associated with tumor size (p > 0.5), MFS (p = 0.5) or CSS (p = 0.4). A trend toward vascular endothelial growth factor pathway enrichment was seen in OSA patients (p = 0.08). CONCLUSIONS: OSA is associated with high Fuhrman grade in patients undergoing surgery for ccRCC. Pending validation of this novel finding in further prospective studies, it could help shape future research to better understand etiological mechanisms associated

The Functional Significance of Catalytic Subunit Vicinal Thiols on Protein Phosphatase 2A: Possible Regulation of Metal Binding Site Availability

Recent findings from this laboratory support the view that the catalytic subunit (PP2Ac) of protein phosphatase 2A contains a redox-sensitive pair of phenylarsine oxide (PAO)-binding vicinal thiols, that form an intrachain disulfide bond in response to oxidative stress, in addition to an apparent redox-resistant pair of PAO-binding vicinal thiols. These earlier observations are in agreement with the known presence on PP2Ac of two sequentially-vicinal pairs of cysteine residues. However, the functional significance of these PAO-binding vicinal thiols is unknown. The present study has examined the possibility that the vicinal thiols of PP2Ac, prepared from rat brain, may play a role in the binding of metal ions. Metal ions are required for catalysis and may also influence PP2A activity allosterically. The results show that a fraction of PP2Ac binds with high-affinity to an immobilized Ni2+-nitrilotriacetic acid (NTA) column, employed here as a convenient probe for metal binding. Moreover, the high-affinity binding of PP2Ac to the immobilized Ni2+ was enhanced by prior incubation with PAO. To examine the possibility that the interaction of PP2Ac with PAO may make available a metal binding site by promoting the release of endogenous catalytic Mn2+ ion, the effect on the phosphatase activity of PP2A of added Mn2+was examined in control and PAO-treated samples. Mn2+ stimulated PP2A activity comparably in both control and PAO-treated samples. Together, these results suggest that the interaction of PP2Ac with the vicinal thiol cross-linker PAO makes available a high-affinity metal-binding site that may be distinct from the binding site for catalytic Mn2+

Can pelvic node dissection at radical prostatectomy influence the nodal recurrence at salvage lymphadenectomy for prostate cancer?

Purpose: To verify the quality of pelvic lymph node dissection (PLND) performed at radical prostatectomy (RP) and its impact on nodal recurrence in patients undergoing salvage lymph node dissection (sLND). Materials and Methods: Retrospective review of 48 patients who underwent sLND for presumed nodal recurrence, to describe the PLND characteristics at RP and correlate the anatomical sites and number of suspicious nodes reported in radiological imaging and final pathology of sLND. Results: Overall, at RP, 8 (16.7%) did not undergo PLND, 32 (66.7%) and 8 (16.7%) received a “limited” (between external iliac vein and obturator nerve) and an “extended” (external iliac, hypogastric, and obturator) dissection, respectively. Median nodes removed during limited and extended dissection were 2 and 24, respectively. At sLND, the mean age was 61.3 years and median prostate specific antigen (PSA) was 1.07 ng/mL. Median nodes removed at sLND were 17 with a median of 2 positive nodes. Recurrent nodes were identified within the template of an extended PLND in 62.5%, 50.0% and 12.5% patients, respectively, following prior no, limited and extended dissection at RP. Recurrence outside the expected lymphatic drainage pathway was noted in 37.5% patients with prior extended dissection at RP. There was a correlation between imaging and pathology specimen in 83% for node location and 58.3% for number of anatomical sites involved. Conclusions: In prostate cancer patients undergoing sLND, most had inadequate PLND at the original RP. Pattern of nodal recurrence may be influenced by the prior dissection and pre sLND imaging appears to underestimate the nodal recurrence

Can We Improve the Preoperative Prediction of Prostate Cancer Recurrence With Multiparametric MRI?

INTRODUCTION: The use of multiparametric magnetic resonance imaging (mpMRI) to assess prostate cancer (PCa) has increased over the past decade. We aimed to assess if preoperative mpMRI lesion score, a variable routinely available for men undergoing pre-biopsy MRI, improves the performance of commonly used preoperative predictive models for PCa recurrence. PATIENTS AND METHODS: We analyzed data from 372 patients with PCa treated with radical prostatectomy in 2012 to 2017 and assessed with pre-biopsy mpMRI within 6 months prior to surgery. Suspicious areas for cancer were scored on a standardized 5-point scale. Cox regression was used to assess the association between mpMRI score and the risk of postoperative biochemical recurrence. Two different models were tested accounting for factors included in the Kattan nomogram and in the D'Amico risk-classification. RESULTS: Overall, 53% and 30% of patients were found with a lesion scored 4 or 5 at pre-biopsy mpMRI, respectively. Risk varied widely by mpMRI (29% 2-year risk of biochemical recurrence for a score of 5 vs. 5% for a score of 1-2), and mpMRI score was associated with large hazard ratios after adjusting for stage, grade, and prostate-specific antigen: 1.66, 1.96, and 2.71 for scores 3, 4, and 5, respectively. However, 95% confidence intervals were very wide (0.19-14.20, 0.26-14.65, and 0.36-20.55, respectively) and included 1. CONCLUSIONS: Our data did not show that preoperative models, commonly used to assess PCa risk, were improved after including the pre-biopsy mpMRI score. However, the value of pre-biopsy mpMRI to improve preoperative risk models should be investigated in larger data sets

Are We Improving Erectile Function Recovery After Radical Prostatectomy? Analysis of Patients Treated over the Last Decade

BACKGROUND: The last decade has seen several advances in radical prostatectomy (RP) technique and post-RP care that are relevant to erectile function (EF) recovery. OBJECTIVE: We examined whether these practice changes have led to observed improvements in EF rates over time. DESIGN, SETTING, AND PARTICIPANTS: We identified 2364 patients treated with either open or minimally-invasive RP at a single academic center in 2008-2015. To mitigate confounding by the surgical learning curve, only patients treated by surgeons who performed at least 100 procedures were considered. INTERVENTION: EF before and after RP was assessed by the International Index of Erectile Function 6 (IIEF-6), with recovery defined as IIEF-6 ≥24. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analyzed EF recovery rates of patients treated with bilateral nerve-sparing surgery and free from adjuvant/salvage treatment at the time of EF assessment. Local polynomial regression analyses explored changes in the outcomes over time. Linear and logistic regression analyses were used to estimate the influence of year of surgery on baseline variables and EF recovery. RESULTS AND LIMITATIONS: We observed a significant decrease over time of the EF recovery rates at both 12 and 24mo post-RP (all p=0.01). However, patient's age at surgery increased over time (mean increase of 0.5 per year; p<0.01), with a resultant increase in risk of comorbidity (odds ratio [OR]=1.1, 95% confidence interval [CI]: 1.02-1.15; p=0.008) and thus decrease in baseline IIEF-6 score (0.35 points per year; p=0.0003). After accounting for baseline and pathological characteristics, urinary function, and type of surgery in a multivariable analysis, year of surgery was not associated with EF recovery (12mo: OR=0.97, 95% CI: 0.91-1.03, p=0.4; 24mo: OR=0.97, 95% CI: 0.91-1.03, p=0.3). CONCLUSIONS: Findings from a high-volume center suggest that, despite the advancements in surgical and postoperative care, EF outcomes after RP have not improved over the last decade. Additional strategies are required to improve EF recovery after RP. PATIENT SUMMARY: The probability of regaining potency after surgery for prostate cancer did not improve over the last decade; more efforts are needed to improve patient's care after radical prostatectomy

The Utilization and Impact of Aromatase Inhibitor Therapy in Men With Elevated Estradiol Levels on Testosterone Therapy

ABSTRACT: Introduction: Testosterone therapy (TTH) for testosterone deficiency (TD) may lead to elevated estradiol (E2) levels requiring management to avoid unnecessary adverse effects. Aim: To examine the impact of aromatase inhibitors, specifically anastrozole (AZ), in men with elevated E2 on TTH. Methods: All patients on TTH at a high volume sexual medicine practice between 2005 and 2019 were reviewed. Men with E2 levels >60 pg/mL regardless of symptoms or 40–60 pg/mL with subjective symptoms were started on AZ 0.5 mg 3x/week. Routine hormone profile and symptom assessment were completed to ensure symptom resolution, reduction of E2 levels and maintenance of testosterone levels. Multivariable logistic regression was completed to determine predictors of men more likely to respond to therapy. Main Outcome Measure: Demographic and hormonal profiles of men on AZ and predictors of response to therapy. Results: 1708 men with TD were placed on TTH. Of these, 51 (3%) were treated with AZ (AZ+). After exclusions, 44 (2.6%) had elevated estradiol levels >60 pg/mL or >40 pg/mL with symptoms. Demographics were similar between groups. TTH distribution between groups was different with greater rates of topical TTH in the AZ- groups (AZ+:34.1% vs AZ-:53.5%) and greater rates of intramuscular TTH in the AZ+ group (AZ+:38.6% vs AZ-:18.5%) (P = .017 overall). Of the 44 men treated with AZ, 68.0% had pre-AZ E2 levels ≥60 pg/mL and 32.0% had levels between 40 and 60 pg/mL. Median pre-AZ E2 levels were 65 (interquartile range [IQR], 55–94) pg/mL in comparison to 22 (IQR 15–38) pg/mL post-AZ E2 levels (P < .001). Total testosterone levels were similar before and after AZ use (616 (IQR 548–846) ng/dL and 596 (IQR 419–798) ng/dL, respectively, P = .926). No statistically significant predictive factors of E2 reduction using AZ were found. Conclusion: While no statistically significant predictors for E2 recovery in men on AZ were found, AZ remains a reasonable option for E2 reduction in men with elevated levels on TTH.Punjani N, Bernie H, Salter C, et al. The Utilization and Impact of Aromatase Inhibitor Therapy in Men With Elevated Estradiol Levels on Testosterone Therapy. Sex Med 2021;9:100378

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