Parenchymal volume preservation during partial nephrectomy: improved methodology to assess impact and predictive factors.

OBJECTIVE: To rigorously evaluate the impact of the percentage of parenchymal volume preserved (PPVP) and how well the preserved parenchyma recovers from ischaemia (Recischaemia ) on functional outcomes after partial nephrectomy (PN) using an accurate and objective software-based methodology for estimating parenchymal volumes and split renal function (SRF). A secondary objective was to assess potential predictors of the PPVP. PATIENTS AND METHODS: A total of 894 PN patients with available studies (2011-2014) were evaluated. The PPVP was measured from cross-sectional imaging at ≤3 months before and 3-12 months after PN using semi-automated software. Pearson correlation evaluated relationships between continuous variables. Multivariable linear regression evaluated predictors of ipsilateral glomerular filtration rate (GFR) preserved and the PPVP. Relative-importance analysis was used to evaluate the impact of the PPVP on ipsilateral GFR preserved. Recischaemia was defined as the percentage of ipsilateral GFR preserved normalised by the PPVP. RESULTS: The median tumour size and R.E.N.A.L. nephrometry score were 3.4 cm and 7, respectively. In all, 49 patients (5.5%) had a solitary kidney. In all, 538 (60%)/251 (28%)/104 (12%) patients were managed with warm/cold/zero ischaemia, respectively. The median pre/post ipsilateral GFRs were 40/31 mL/min/1.73 m2 , and the median (interquartile range [IQR]) percentage of ipsilateral GFR preserved was 80% (71-88%). The median pre/post ipsilateral parenchymal volumes were 181/149 mL, and the median (IQR) PPVP was 84% (76-92%). In all, 330 patients (37%) had a PPVP of <80%, while only 34 (4%) had a Recischaemia of <80%. The percentage of ipsilateral GFR preserved correlated strongly with the PPVP (r = 0.83, P < 0.01) and loss of parenchymal volume accounted for 80% of the loss of ipsilateral GFR. Multivariable analysis confirmed that the PPVP was the strongest predictor of ipsilateral GFR preserved. Greater tumour size and endophytic and nearness properties of the R.E.N.A.L. nephrometry score were associated with a reduced PPVP (all P ≤ 0.01). Solitary kidney and cold ischaemia were associated with an increased PPVP (all P < 0.05). CONCLUSIONS: A reduced PPVP predominates regarding functional decline after PN, although a low Recischaemia can also contribute. Tumour-related factors strongly influence the PPVP, while surgical efforts can improve the PPVP as observed for patients with solitary kidneys.

Body morphometry may predict parastomal hernia following radical cystectomy with ileal conduit.

OBJECTIVE: To investigate whether preoperative body morphometry analysis can identify patients at risk of parastomal hernia (PH), which is a common complication after radical cystectomy (RC). PATIENTS AND METHODS: All patients who underwent RC between 2010 and 2020 with available cross-sectional imaging preoperatively and at 1 and 2 years postoperatively were included. Skeletal muscle mass and total fat mass (FM) were determined from preoperative axial computed tomography images obtained at the level of the L3 vertebral body using Aquarius Intuition software. Sarcopenia and obesity were assigned based on consensus definitions of skeletal muscle index (SMI) and FM index (FMI). PH were graded using both the Moreno-Matias and European Hernia Society criteria. Binary logistic regression and recursive partitioning were used to identify patients at risk of PH. The Kaplan-Meier method with log-rank and Cox proportional hazards models included clinical and image-based parameters to identify predictors of PH-free survival. RESULTS: A total of 367 patients were included in the final analysis, with 159 (43%) developing a PH. When utilising binary logistic regression, high FMI (odds ratio [OR] 1.63, P < 0.001) and low SMI (OR 0.96, P = 0.039) were primary drivers of risk of PH. A simplified model that only relied upon FMI, SMI, and preoperative albumin improved the classification of patients at risk of PH. On Kaplan-Meier analysis, patients who were obese or obese and sarcopenic had significantly worse PH-free survival (P < 0.001). CONCLUSION: Body morphometry analysis identified FMI and SMI to be the most consistent predictors of PH after RC.

Parenchymal volume analysis to assess longitudinal functional decline following partial nephrectomy.

OBJECTIVE: To identify factors associated with longitudinal ipsilateral functional decline after partial nephrectomy (PN). PATIENTS AND METHODS: Of 1140 patients managed with PN (2012-2014), 349 (31%) had imaging/serum creatinine levels pre-PN, 1-12 months post-PN (new baseline), and >3 years later necessary for inclusion. Parenchymal-volume analysis was used to determine split renal function. Patients were grouped as having significant renal comorbidity (CohortSRC : diabetes mellitus with insulin-dependence or end-organ damage, refractory hypertension, or severe pre-existing chronic kidney disease) vs not having significant renal comorbidity (CohortNoSRC ) preoperatively. Multivariable regression was used to identify predictors of annual ipsilateral parenchymal atrophy and functional decline relative to new baseline values post-PN, after the kidney had healed. RESULTS: The median follow-up was 6.3 years with 87/226/36 patients having cold/warm/zero ischaemia. The median cold/warm ischaemia times were 32/22 min. Overall, the median tumour size was 3.0 cm. The preoperative glomerular filtration rate (GFR) and new baseline GFR (NBGFR) were 81 and 71 mL/min/1.73 m2 , respectively. After establishment of the NBGFR, the median loss of global and ipsilateral function was 0.7 and 0.4 mL/min/1.73 m2 /year, respectively, consistent with the natural ageing process. Overall, the median ipsilateral parenchymal atrophy was 1.2 cm3 /year and accounted for a median of 53% of the annual functional decline. Significant renal comorbidity, age, and warm ischaemia were independently associated with ipsilateral parenchymal atrophy (all P < 0.01). Significant renal comorbidity and ipsilateral parenchymal atrophy were independently associated with annual ipsilateral functional decline (both P < 0.01). Annual median ipsilateral parenchymal atrophy and functional decline were both significantly increased for CohortSRC compared to CohortNoSRC (2.8 vs 0.9 cm3 , P < 0.01 and 0.90 vs 0.30 mL/min/1.73 m2 /year, P < 0.01, respectively). CONCLUSIONS: Longitudinal renal function following PN generally follows the normal ageing process. Significant renal comorbidities, age, warm ischaemia, and ipsilateral parenchymal atrophy were the most important predictors of ipsilateral functional decline following establishment of NBGFR.

Functional recovery after partial nephrectomy: next generation analysis.

OBJECTIVES: To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia. PATIENTS AND METHODS: Of 1140 patients managed with PN (2012-2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia. RESULTS: In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range [IQR]) ischaemia times for cold and warm ischaemia of 30 (25-42) and 22 (18-28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63-92) and 69 (54-81) mL/min/1.73 m2 , respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33-47) and 31 (24-38) mL/min/1.73 m2 , respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5-12) mL/min/1.73 m2 with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%-102%), 95% (89%-101%), and 97% (91%-102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin-dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score. CONCLUSIONS: The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia-related factors that are also independently associated with impaired recovery, although altogether these were much less impactful.

Art Heals: Randomized Controlled Study Investigating the Effect of a Dedicated In-house Art Gallery on the Recovery of Patients After Major Oncologic Surgery.

INTRODUCTION: We sought to investigate the effect of exposure to a dedicated art gallery during the perioperative period on the recovery of patients undergoing major oncologic procedures. METHODS: Eighty patients were randomized into 2 arms; standard of care versus exposure to art. All patients completed a survey assessing their baseline art knowledge, and 4 poststudy validated questionnaires assessing their pain (Pain Rating Scale), hope (Herth Hope Index), anxiety (State-Trait Anxiety Inventory for Adults), and mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale). A linear model adjusted for baseline scores was run comparing the scores among the 2 study arms. Stepwise multivariate regression analyses were used to identify predictors of improved pain, hope, anxiety, and wellbeing. RESULTS: Both groups were comparable in terms of demographics, passion, and knowledge about art. There was no statistically significant difference in pain scores between the 2 groups. The exposure to art group experienced higher hope (2.4 points higher vs 0.05, P = 0.004), lower anxiety (8 points lower vs -0.9, P < 0.0001), and higher mental well-being scores (5.23 points higher vs -0.05, P < 0.0001) in comparison to the standard of care group. On multivariate analyses, exposure to art was significantly associated with improved hope, anxiety, and mental well-being after adjusting for patient and disease characteristics. CONCLUSIONS: Dedicated exposure to art was associated with improved hope, anxiety, and mental well-being of patients after major oncologic surgery.

Pathologic and Short-Term Oncologic Outcomes of Prostate Cancer Patients Following Transvesical Robot-Assisted Radical Prostatectomy.

PURPOSE: To study the pathologic and short-term oncological and survival outcomes following Transvesical Single-Port Robot-Assisted Radical Prostatectomy. MATERIALS AND METHODS: A retrospective review was performed on prospectively collected data on 169 patients with low and intermediate-risks prostate cancer, who either underwent Single-Port Transvesical or Multi-Port Transperitoneal Radical Prostatectomy by a single surgeon between 2015 and 2022. Preoperative clinicopathologic characteristics, as well as final histopathology outcomes, were compared. Univariate Cox proportional hazard analysis was used to evaluate the impact of the surgical approach on biochemical recurrence-free survival within 12 months. RESULTS: Single-Port Transvesical and Multi-Port Transperitoneal Robotic Radical Prostatectomy were completed in 85 and 84 patients, respectively. Preoperative clinicopathologic features were similar between the 2 groups. In terms of histopathology outcomes, the 2 groups had identical final Gleason Grades, T stage, as well as the rates of adverse pathological features and positive surgical margins (P = >0.05). Despite the lower median number of nodes in the single-port cohort of 2 (0-5) compared to 6 (4-9) in the multi-port cohort (P = <0.001), there remained no statistically significant difference in the rates of lymph node invasion (P = 0.08). At a median follow-up of 12 months, there were no differences in the biochemical recurrence-free survival rates among both groups (P = 0.38). Univariate Cox proportional hazard analysis did not consider surgical approach to be an independent predictor of biochemical recurrence (HR 0.53, 95%CI 0.13-2.23, P = 0.39). CONCLUSION: In well-selected patients, single-port transvesical robotic radical prostatectomy provided a similar short-term oncologic control as the multi-port approach with similar surgical margin status and 1-year biochemical recurrence rates.

An exploratory study investigating the impact of the bladder tumor microbiome on Bacillus Calmette Guerin (BCG) response in non-muscle invasive bladder cancer.

PURPOSE: Intravesical Bacillus Calmette-Guerin (BCG) is standard of care for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC). The effect of the bladder microbiome on response to BCG is unclear. We sought to characterize the microbiome of bladder tumors in BCG-responders and non-responders and identify potential mechanisms that drive treatment response. MATERIALS AND METHODS: Patients with archival pre-treatment biopsy samples (2012-2018) were identified retrospectively. Prospectively, urine and fresh tumor samples were collected from individuals with high-risk NMIBC (2020-2023). BCG response was defined as tumor-free 2 years from induction therapy. Extracted DNA was sequenced for 16S rRNA and shotgun metagenomics. Primary outcomes were species richness (α-diversity) and microbial composition (ß-diversity). Paired t-tests were performed for α-diversity (Observed species/Margalef). Statistical analysis for ß-diversity (weighted and unweighted UniFrac distances, weighted Bray-Curtis dissimilarity) were conducted through Permanova, with 999 permutations. RESULTS: Microbial species richness (P < 0.001) and composition (P = 0.001) differed between BCG responders and non-responders. Lactobacillus spp. were significantly enriched in BCG-responders. Shotgun metagenomics identified possible mechanistic pathways such as assimilatory sulfate reduction. CONCLUSION: A compositional difference exists in the tumor microbiome of BCG responders and non-responders with Lactobacillus having increased abundance in BCG responders.

Oncologic outcomes of intravesical therapy in the management of nonmuscle invasive bladder cancer with variant histology.

PURPOSE: There is limited data on oncologic outcomes in nonmuscle invasive bladder cancer (NMIBC) with variant histology (VH) managed with intravesical therapy. We sought to evaluate oncologic outcomes for this cohort at a high-volume center. MATERIALS AND METHODS: A retrospective review of an IRB-approved bladder cancer database was performed. Patients with a history of NMIBC with VH present on transurethral resection of bladder tumor (TURBT) treated with intravesical therapy (BCG or chemotherapy) were identified. Outcomes of interest included recurrence within the bladder, progression to muscle-invasive bladder cancer (MIBC), metastatic progression, cancer-specific, and overall survival. Survival time was computed from the date of initiation of intravesical therapy to the date of event or censoring. For patients who underwent radical cystectomy, recurrence-free, cancer-specific, and overall survival were also computed. The Kaplan-Meier method with log rank was utilized to compare survival time between VH sub-groups. RESULTS: Ninety patients were included in the final cohort with a median follow-up of 38 months. The majority of patients had T1 disease (72%) and received intravesical BCG (83%) as their only form of intravesical therapy. The most commonly represented VH in this series were glandular and squamous differentiation (26%). Forty-eight patients (53%) experienced recurrence within the bladder with a median recurrence-free survival of 24 months (95% Confidence Interval [CI]: 2-46 months). Five-year rates of progression to MIBC and distant metastasis were both 14% respectively. Twenty-six patients (28%) eventually required cystectomy. When stratifying by VH, patients with sarcomatoid, plasmacytoid, and micropapillary had significantly worse oncologic outcomes. CONCLUSION: In this series of highly-selected patients with NMIBC and VH, bladder-sparing treatment with intravesical therapy demonstrated acceptable oncologic outcomes for most VHs. This may be an acceptable treatment option for patients without plasmacytoid, sarcomatoid, or micropapillary features who are not suitable cystectomy candidates or who prioritize bladder-sparing treatment.

Parenchymal obliteration by renal masses: Functional and oncologic implications.

OBJECTIVES: Most renal tumors merely displace nephrons while others can obliterate parenchyma in an invasive manner. Substantial parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) may have oncologic implications; however, studies regarding PVR remain limited. Our objective was to evaluate the oncologic implications associated with PVR using improved methodology including more accurate and objective tools. PATIENTS/METHODS: A total of 1,222 patients with non-metastatic renal tumors managed with partial nephrectomy (PN) or radical nephrectomy (RN) at Cleveland Clinic (2011-2014) with necessary studies were retrospectively evaluated. Parenchymal volume analysis via semiautomated software was used to estimate split renal function and preoperative parenchymal volumes. Using the contralateral kidney as a control, %PVR was defined: (parenchymal volumecontralateral-parenchymal volumeipsilateral) normalized by parenchymal volumecontralateral x100%. PVR was determined preoperatively and not altered by management. Patients were grouped by degree of PVR: minimal (<5%, N = 566), modest (5%-25%, N = 414), and prominent (≥25%, N = 142). Kaplan-Meier was used to evaluate survival outcomes relative to degree of PVR. Multivariable Cox-regression models evaluated predictors of recurrence-free survival (RFS). RESULTS: Of 1,122 patients, 801 (71%) were selected for PN and 321 (29%) for RN. Overall, median tumor size was 3.1 cm and 6.8 cm for PN and RN, respectively, and median follow-up was 8.6 years. Median %PVR was 15% (IQR = 6%-29%) for patients selected for RN and negligible for those selected for PN. %PVR correlated inversely with preoperative ipsilateral GFR (r = -0.49, P < 0.01) and directly with advanced pathologic stage, high tumor grade, clear cell histology, and sarcomatoid features (all P < 0.01). PVR≥25% associated with shortened recurrence-free, cancer-specific, and overall survival (all P < 0.01). Male sex, ≥pT3a, tumor grade 4, positive surgical margins, and PVR≥25% independently associated with reduced RFS (all P < 0.02). CONCLUSIONS: Obliteration of normal parenchyma by RCC substantially impacts preoperative renal function and patient selection. Our data suggests that increased PVR is primarily driven by aggressive tumor characteristics and independently associates with reduced RFS, although further studies will be needed to substantiate our findings.

The combination of prostate MRI PI-RADS scoring system and a genomic classifier is associated with pelvic lymph node metastasis at the time of radical prostatectomy.

OBJECTIVE: Pelvic lymph node metastasis (PLNM) at the time of radical prostatectomy (RP) portends an unfavorable prognosis in prostate cancer patients. Conventional and advanced imaging remains limited in its ability to detect PLNM. We sought to evaluate the combination of a genomic classifier Decipher with Prostate Imaging Reporting and Data System (PI-RADS) scores in improving the detection of PLNM. METHODS: A retrospective review was performed of patients whom underwent RP, Decipher analysis, and pre-operative prostate MRI. Categorical variables were compared using Pearson chi-squareχ2 tests. Quantitative variables were assessed with Wilcoxon rank-sum tests. Multivariable logistic regression was used to identify predictors of PLNM on final pathology. RESULTS: In total, 202 patients were included in the analysis, 23 of whom (11%) had PLNM. Patients with PLNM had higher median Decipher scores (0.73) than those without PLNM (0.61; p = 0.003). Patients with PLNM were more likely to demonstrate PI-RADS scores ≥ 4 (96%) than those without PLNM (74%; p = 0.012). Logistic regression demonstrated an interaction between Decipher score with PI-RADS score ≥4 (OR = 20.41; 95% CI, 2.10-198.74; p = 0.009) The combination demonstrated an area under the curve (AUC) of 0.73 (95% CI, 0.63-0.82; p < 0.001) for predicting PLNM. CONCLUSION: The combination of elevated Decipher genomic score (≥ 0.6) and clinically significant PI-RADS score (≥ 4) is associated with PLNM at the time of RP in a modern high-risk cohort of patients with PCaprostate cancer. ADVANCES IN KNOWLEDGE: Prostate MRI and genomic testing may help identify patients with adverse pathology.

Outcomes of Inflatable Penile Prosthesis following Radical Cystectomy: A Matched Cohort Analysis.

OBJECTIVE: To evaluate outcomes of inflatable-penile-prosthesis (IPP) implantation after radical-cystectomy compared to other etiologies of erectile dysfunction. MATERIALS AND METHODS: All IPPs within the past 20 years in a large regional health system were reviewed, and erectile dysfunction (ED) etiology was determined as radical-cystectomy, radical-prostatectomy, or organic/other ED. Cohorts were generated by 1:3 propensity score match using age, body mass index, and diabetes status. Baseline demographics and relevant comorbidities were evaluated. Clavien-Dindo complications, grade, and reoperation were assessed. Multivariable logarithmic regression was used to identify the predictors of 90-day complications following IPP implantation. Log-rank analysis was used to assess the time-to-reoperation after IPP implantation in patients with a history of cystectomy compared with noncystectomy etiologies. RESULTS: Of 2600 patients, 231 subjects were included in the study. Comparing patients undergoing IPP for cystectomy vs pooled noncystectomy indications, those who underwent radical-cystectomy had a higher overall complication rate (24% vs 9%, p = 0.02). Clavien-Dindo complication grades did not differ across groups. Reoperation was significantly more common following cystectomy (cystectomy: 21% vs noncystectomy: 7%, p = 0.01), however time to reoperation did not differ significantly by indication (cystectomy: 8 years vs noncystectomy: 10 years,p = 0.09). Among cystectomy patients, 85% of reoperations were due to mechanical failure. CONCLUSION: Compared to other erectile dysfunction etiologies, patients undergoing IPP with a history of cystectomy have an increased risk of complications within 90-days of implantation and need for surgical device revision, but no greater risk for high-grade complications. Overall IPP remains a valid treatment option after cystectomy.

The Feasibility and Value of a Focal Therapy Multidisciplinary Tumor Board, Including Radiographic and Pathological Overreads in Refining the Selection for High Intensity Focused Ultrasound in Prostate Cancer Patients.

INTRODUCTION: Focal therapy for prostate cancer is increasingly recognized as an acceptable therapeutic option in well-selected men. A focal therapy multidisciplinary tumor board geared toward improving patient selection is a novel concept which has not been reported. We describe our institution's initial experience with a multidisciplinary tumor board for focal therapy and its outcomes in terms of patient selection. METHODS: This was a single-center, prospective study of patients referred to a multidisciplinary tumor board. All prostate MRIs were re-reviewed by a single radiologist with >10 years of experience, and the number, size, location, and Prostate Imaging Reporting & Data System scores of lesions visible on MRI were recorded and compared to the original report. Outside histopathology, when requested, was also re-reviewed for cancer grade groups and adverse pathological features. A descriptive statistical analysis was performed. RESULTS: Seventy-four patients were presented at our multidisciplinary tumor board (January-October 2022). Sixty-seven patients were treatment naïve, while 7 had prior radiation±androgen deprivation therapy. MRI overread was performed on all treatment-naïve patients (67/74 [91%]), while pathology overreads were performed on 14/74 (19.9%). Following multidisciplinary tumor board, 19 patients (25.6%) were deemed suitable candidates for focal therapy. A total of 24 patients (35.8%) were not deemed candidates for high intensity focused ultrasound focal therapy based exclusively on findings identified at MRI overread. Pathology re-review changed management for 3/14 patients, with two-thirds being downgraded to grade group 1 disease and opting for active surveillance. CONCLUSIONS: Multidisciplinary tumor board for focal therapy is feasible. MRI overread is an essential component of this process and demonstrates significant findings that alter eligibility or management in over a third of patients.

Using IsoPSA With Prostate Imaging Reporting and Data System Score May Help Refine Biopsy Decision Making in Patients With Elevated PSA.

OBJECTIVE: To assess how IsoPSA, a structure-based serum assay which has been prospectively validated in detecting clinically significant prostate cancer (csPCa), can help the biopsy decision process when combined with the prostate imaging reporting and data systems (PI-RADS). MATERIALS AND METHODS: This was a single-center retrospective review of prospectively collected data on patients receiving IsoPSA testing for elevated PSA (>4.0ng/mL). Patients were included if they had received an IsoPSA test and prostate MRI within 1 year of IsoPSA testing, and subsequently underwent prostate biopsy. Multivariable logistic regression was used to identify predictors of (csPCa, ie, GG ≥ 2) on biopsy. Predictive probabilities for csPCa at biopsy were generated using IsoPSA and various PI-RADS scores. RESULTS: Two hundred and 7 patients were included. Twenty-two percent had csPCa. Elevated IsoPSA ratio (defined as ≥6.0) (OR: 5.06, P = .015) and a PI-RADS 4-5 (OR: 6.37, P <.001) were significant predictors of csPCa. The combination of elevated IsoPSA ratio and PI-RADS 4-5 lesion had the highest area under the curve (AUC) (AUC: 0.83, P <.001). The predicted probability of csPCa when a patient had a negative or equivocal MRI (PI-RADS 1-3) and a low IsoPSA ratio (≤6) was <5%. CONCLUSION: The combination of PI-RADS with IsoPSA ratios may help refine the biopsy decision-making process. In our cohort, a negative or equivocal MRI with a low IsoPSA may provide a low enough predicted probability to omit biopsy in such patients.

Intratumoral androgen biosynthesis associated with 3ß-hydroxysteroid dehydrogenase 1 promotes resistance to radiotherapy in prostate cancer.

Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy of an adrenal-permissive HSD3B1 (1245C) allele, which increases levels of 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) and promotes intracellular androgen biosynthesis. Germline inheritance of the adrenally permissive allele confers worse outcomes in men with advanced PCa. We investigated whether HSD3B1 (1245C) drives resistance to combined androgen deprivation and radiotherapy. Adrenally permissive 3ßHSD1 enhanced resistance to radiotherapy in PCa cell lines and xenograft models engineered to mimic the human adrenal/gonadal axis during androgen deprivation. The allele-specific effects on radiosensitivity were dependent on availability of DHEA, the substrate for 3ßHSD1. In lines expressing the HSD3B1 (1245C) allele, enhanced expression of DNA damage response (DDR) genes and more rapid DNA double-strand break (DSB) resolution were observed. A correlation between androgen receptor (AR) expression and increased DDR gene expression was confirmed in 680 radical prostatectomy specimens. Treatment with the nonsteroidal antiandrogen enzalutamide reversed the resistant phenotype of HSD3B1 (1245C) PCa in vitro and in vivo. In conclusion, 3ßHSD1 promotes prostate cancer resistance to combined androgen deprivation and radiotherapy by upregulating DNA DSB repair. This work supports prospective validation of early combined androgen blockade for high-risk men harboring the HSD3B1 (1245C) allele.

Elevated IsoPSA Selects for Clinically Significant Prostate Cancer Without a Preference for Any Particular Adverse Histopathologic or Radiographic Feature.

OBJECTIVE: To explore if elevated IsoPSA selects for particular adverse radiographic or histopathologic features among men destined to undergo radical prostatectomy (RP) because of clinically significant prostate cancer identified at biopsy. MATERIALS AND METHODS: Single center, retrospective review of patients who had undergone IsoPSA testing, prostate biopsy and RP at our institution from 2019-2021. A consecutive cohort of patients whom had undergone RP within the same period without pre-operative IsoPSA served as controls. Pre-operative prostate Magnetic Resonance Imaging (MRI) was included in our analysis. Adverse histopathologic and MRI features were compared between both groups. Concordance, downstaging, and upstaging grade group rates (GG) was evaluated. Pearson Chi-Square test was used to compare categorical variables, Wilcoxon-Rank sum test for quantitative variables, and binary logistic regression to identify predictors of upstaging at RP. RESULTS: Eighty-three patients underwent IsoPSA and RP while 44 patients were controls. The IsoPSA group had significantly higher pre-operative PSA (IsoPSA group: 7.8 ng/mL vs Control group: 5.2 ng/mL, P<.001 ). Elevated IsoPSA index (>6.0) did not select for any specific adverse histopathologic features at RP. Excluding PSA density, elevated IsoPSA was not selective for adverse MRI features. There were no differences in concordance, downstaging, and upstaging GG rates from biopsy to RP. IsoPSA testing was not a predictor of GG upstaging (Odds Ratio: 0.63, P .58). CONCLUSION: Elevated IsoPSA is a diagnostic tool that can detect clinically significant prostate at the time of biopsy. In doing so, it does not select for any particular adverse prostate MRI or pathologic feature at RP.

Transcriptomic Features of Cribriform and Intraductal Carcinoma of the Prostate.

BACKGROUND: Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes. OBJECTIVE: The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (>0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status. RESULTS AND LIMITATIONS: A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p < 0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p < 0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p < 0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p = 0.046). Other enriched pathways included E2F targets (NES: 1.69, p = 0.031) and oxidative phosphorylation (NES: 1.68, =0 .033). CONCLUSIONS: This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures. PATIENT SUMMARY: Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.

Ability of the surgical Apgar score to predict acute kidney injury following radical cystectomy.

PURPOSE: Acute kidney injury (AKI) is a common complication after radical cystectomy (RC). Previous literature has shown that intraoperative hemodynamic instability measured via the surgical Apgar score is an independent predictor of major complications following RC. We sought to determine whether the surgical Apgar score is predictive of postoperative AKI. METHODS: We performed a retrospective review of RC patients at our institution from 2010 to 2017. Intraoperative hemodynamic instability was captured via the Apgar score based on the lowest intraoperative mean arterial blood pressure, lowest heart rate, and estimated blood loss. Patients were divided into 3 groups: high-risk (HR; Apgar ≤4), intermediate-risk (IR; Apgar score 5-6), and low-risk (LR; Apgar score ≥7). AKIs were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. High grade AKIs were defined as KDIGO grade 2 or 3. Categorical variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test, and multivariable logistic regression to identify predictors of AKI and high grade AKIs within 30 days of RC. RESULTS: Eight hundred and seventy-three patients were included with a median follow-up of 35 months. AKI within 30 days was observed in 28% of patients. Predictors of AKI within 30 days on adjusted analysis included IR (OR: 1.83, P = 0.002) and HR (OR: 3.53, P < 0.001) Apgar scores. IR (OR: 2.23, P = 0.007) and HR (OR: 4.87, P < 0.001) Apgar scores were also predictors of high-grade AKIs. CONCLUSION: Intraoperative hemodynamic instability measured via the Apgar score can be predictive of AKI, which can guide individualized fluid management in the postoperative period.

Survival outcomes following radical cystectomy in patients with prior pelvic radiation for prostate cancer: A matched cohort analysis.

OBJECTIVES: To determine the impact of prior pelvic radiation therapy (XRT) on outcomes following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: We performed a retrospective review comparing patients with bladder cancer requiring RC and prior history of XRT for prostate cancer to those undergoing RC without XRT history at our institution from 2011-2018. Propensity score matching was performed with the following variables: age, chronic kidney disease, nutritional deficiency, neoadjuvant chemotherapy use, Charlson comorbidity index, surgical approach, urinary diversion type, and pathologic T-stage. Perioperative, pathologic and oncologic outcomes were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Categorical variables were assessed utilizing the Pearson Chi Square Test, and continuous variables with the Wilcoxon rank-sum test. The Kaplan-Meier method with stratified-log rank was used to compare survival outcomes. Multivariable Cox proportional hazards models were utilized to identify predictors of overall and recurrence free survival. RESULTS: 227 patients were included, of which 47 had radiotherapy for prostate cancer. 47% of patients in the radiation cohort received external beam radiation therapy, 47% received brachytherapy and 7% received both. There were no differences in recurrence-free survival (P = 0.82) or overall survival (P = 0.25). Statistically significant differences in perioperative or postoperative outcomes such as 90-day complication, readmission, mortality rates, or ureteroenteric anastomotic stricture rates were not found. Rates of node-positive disease, median lymph node yield, positive surgical margin rates, lymphovascular invasion, or variant histology were not significantly different between cohorts. CONCLUSIONS: After matching for T-stage and other clinical variables, history of pelvic XRT for prostate cancer in patients who later required RC for bladder cancer, was not associated with an increased rate of perioperative complications or an independent predictor of RFS or OS.

Comparing Pathologic and Survival Outcomes Between Primary and Secondary Muscle Invasive Bladder Cancer When Treated by Radical Cystectomy With or Without Neoadjuvant Chemotherapy.

OBJECTIVE: To compare pathologic and survival outcomes between primary muscle invasive (pMIBC) and secondary muscle invasive (sMIBC) bladder cancer patients who were treated with or without cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). METHODS: We reviewed cT2-T4/N0 MIBC patients at our institution between 2010-2019. pMIBC was defined as presenting with > cT2 disease on initial or restaging TURBT with no prior history of bladder cancer. sMIBC was defined as prior history of NMIBC that was treated with at least one induction course of BCG that progressed to MIBC. Outcomes analyzed included pathologic downstaging rates defined as pT2 and N+ disease were predictors of poorer CSS and OS. Separate analysis of sMIBC patients whom underwent RC only (N = 61), demonstrated inferior oncologic outcomes to other cohorts (P < .01). CONCLUSION: There were no differences in pathologic response or survival between pMIBC and sMIBC patients when managed with NAC and RC.

The role of enhanced recovery after surgery protocols in the development of acute kidney injury following radical cystectomy.

PURPOSE: Recent reports have suggested that fluid restriction as part of Enhanced Recovery after Surgery (ERAS) pathways may increase the risk of AKI in radical cystectomy (RC) patients. We sought to evaluate the impact of ERAS initiation on AKI incidence at a high-volume tertiary care center. MATERIALS AND METHODS: We performed a retrospective review of our IRB approved database to identify patients receiving RC from 2010 to 2019. ERAS was initiated at our institution in October 2016. Acute kidney injuries were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria and must have occurred within 7 days of indexed RC. Estimated glomerular filtration rate (eGFR) was captured at baseline, 1, 3, 6, and 12 months respectively. Categorical variables were compared with the Pearson-Chi square test. Quantitative variables were analyzed with the Wilcoxon-Rank sum test. Multivariable binary logistic regression and interaction analysis was used to identify predictors of AKI. RESULTS: Twelve hundred patients were included. Twenty-two percent of patients experienced an AKI within 7 days. Patients in the ERAS cohort experienced less AKIs after RC (18% vs. 25%, P = 0.003). When adjusting for year of surgery, ERAS was not a significant predictor for AKI on multivariable analysis (OR: 0.87, P = 0.73). On interaction analysis, during the ERAS era, intracorporeal robot-assisted radical cystectomy (iRARC) was associated with decreased odds of AKI (OR: 0.39, P = 0.034). There were no significant differences in eGFR at 12 months postoperatively (P = 0.16). CONCLUSION: Unlike previous reports, ERAS initiation was not associated with increased risk of AKI at a tertiary care high-volume center.