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.

Value of Partial Nephrectomy for Renal Cortical Tumors of cT2 or Greater Stage: A Risk-benefit Analysis of Renal Function Preservation Versus Increased Postoperative Morbidity.

BACKGROUND: Indications for partial nephrectomy (PN) have expanded to include larger tumors. Compared with radical nephrectomy (RN), PN reduces the risk of chronic kidney disease but is associated with higher morbidity. OBJECTIVE: To explore whether the benefit of PN (preservation of estimated glomerular filtration rate [eGFR] ≥60ml/min/1.73m2 1yr postoperatively) over RN is offset by higher morbidity for cT2-cT3a tumors. DESIGN, SETTING, AND PARTICIPANTS: A total of 1921 patients with renal cortical tumors who underwent nephrectomy between 2000 and 2012 were analyzed, with 297 having clinical stage T2 or higher disease. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression models adjusted for age, tumor size, and comorbidities were used to calculate the risk of complications within 90d and the risk of low eGFR across a range of tumor sizes. Models were created separately for RN and PN, and the difference between risk estimates was calculated. RESULTS AND LIMITATIONS: For tumors with diameters between 7 and 12cm, the risk of eGFR downgrade associated with RN was higher than the risk of complications associated with PN. The magnitude of the risk of eGFR downgrade was similar to the magnitude of complications risk across all tumor sizes. Our analysis was performed at a single institution, and used only tumor size to compare the risk and benefits of surgery. CONCLUSIONS: Our study suggests that PN is associated with higher eGFR preservation than RN for cT2 or greater renal tumors. The magnitude of this advantage offsets the higher morbidity observed with PN. PATIENT SUMMARY: When treating a large kidney tumor, it is difficult to decide whether it is better to remove the whole kidney or remove just the tumor. The second option improves postoperative renal function but is more complex. We tried to find whether there is a tumor size at which one technique should be used over the other.

Extensive disease among potential candidates for hemi-ablative focal therapy for prostate cancer.

OBJECTIVE: To examine a set of proposed eligibility factors for hemi-ablative focal therapy in prostate cancer and to determine the likelihood of residual extensive disease. METHODS: We retrospectively analyzed data from 98 patients with unilateral prostate cancer on biopsy with detailed tumor maps from whole-mount slides and preoperative magnetic resonance imaging data. These patients met the focal therapy consensus meeting inclusion criteria (prostate-specific antigen <15 ng/mL, clinical stage T1c-T2a and Gleason score 3 + 3 or 3 + 4 on needle biopsy), and underwent radical prostatectomy between 2000 and 2014. Extensive disease was defined as having Gleason pattern 4/5 in bilateral lobes, any extraprostatic extension, seminal vesicle invasion or lymph node invasion. Both lobes of the prostate were scored on magnetic resonance imaging. Preoperative characteristics including biopsy and magnetic resonance imaging data were used to predict extensive disease. RESULTS: Among our cohort of 98 patients, 40% (95% CI 30-50%) had extensive disease. A total of 33% (95% CI 24-43%) had Gleason pattern 4/5 in both lobes with a median Gleason pattern 4/5 tumor volume in the biopsy negative lobe of 0.06 cm3 , 17 patients had pathological tumor stage ≥3 and one patient had lymph node invasion. CONCLUSIONS: An important number of patients meeting the focal therapy consensus meeting inclusion criteria can present extensive disease. Further studies using targeted biopsies might provide more accurate information about the selection of focal therapy candidates.

Disease Control With Delayed Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy.

Purpose: To retrospectively assess clinical outcomes and toxicity profile of prostate cancer patients treated with delayed dose-escalated image-guided salvage radiotherapy (SRT) for macroscopic local recurrence after radical prostatectomy (RP). Material and Methods: We report on a cohort of 69 consecutive patients with local recurrence after RP and no evidence of regional or distant metastasis who were referred for salvage radiotherapy between 2007 and 2016. SRT consisted of 64-66 Gy (2 Gy/fraction) to the prostatic bed followed by dose escalation to 72-74 Gy (2Gy/fraction) to the macroscopic disease. All patients received concurrent short-term androgen deprivation therapy (ADT). Biochemical recurrence-free survival (bRFS) and clinical progression-free-survival (cPFS) were depicted using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predictors of survival outcomes. Baseline, acute, and late urinary and gastrointestinal (GI) toxicity rates were reported using CTCAE v4.03. Results: Median time from RP to SRT was 66 months (IQR: 32-124). Median pre-SRT prostate-specific antigen (PSA) was 2.7 ng/ml (IQR: 0.9-6.5). Median follow-up after SRT was 38 months (IQR: 24-66). The 3- and 5-year bRFS were 58 and 44%, respectively. The 3- and 5-year cPFS were 91 and 76%, respectively. Median time from SRT to clinical disease progression was 102 months (IQR 77.5-165). At baseline, 3 patients (4%) had grade 3 urinary symptoms. Six patients (9%) developed acute and six patients (9%) developed late grade 3 urinary toxicity. Five patients (7%) had acute grade 2 GI toxicity. No acute grade 3 GI toxicity was reported. Late grade 3 GI toxicity was reported in one patient (1.5%). Conclusions: Delayed dose-escalated SRT combined with short-course ADT for macroscopic LR after RP was associated with 44% bRFS and 76% cPFS at 5 years. Albeit improved patient stratification is warranted, these data suggest that delayed SRT provides inferior tumor control compared to early intervention.

Repeat prostate biopsies prior to radical prostatectomy do not impact erectile function recovery and mid- to long-term continence.

BACKGROUND: A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long-term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy. METHODS: From 1996 to 2015, 1015 consecutive patients underwent radical prostatectomy, and subsequently had urinary continence and erectile function assessed for >2 years follow-up. One-fourth of patients (275; 27%) had ≥2 biopsies before prostatectomy. Logistic regression models tested whether repeat biopsy before prostatectomy predicted continence or erectile function recovery. RESULTS: For the overall cohort, continence rates were 84%, 92%, 96%, and 98% at 3, 6, 12, and 24 months, respectively. Repeat biopsy before prostatectomy was associated with lower continence rate at 3 months compared to single biopsy (P = 0.03); however, no significant differences were observed at 6, 12, or 24 months. In multivariable analyses adjusting for age, body mass index and diabetes/cardiovascular disease/smoking, the association between repeat biopsy and lower likelihood of continence at 3 months remained (odds ratio 0.67, 95% confidence interval 0.47-0.97; P = 0.03). Overall erectile function recovery rates were 16%, 33%, 51%, and 55% at 3, 6, 12, and 24 months, respectively. No difference in erectile function recovery rates was seen at any time point for single biopsy versus repeat biopsy. In multivariable analyses, repeat biopsy was not predictive of erectile function recovery at any time point. CONCLUSIONS: Repeat biopsy before radical prostatectomy impairs early continence after surgery. However, erectile function recovery and mid-term to long-term continence are not affected. These data support the current trend towards active surveillance and delayed local treatment in patients with low- to intermediate-risk prostate cancer.

Nerve-sparing radical cystectomy has a beneficial impact on urinary continence after orthotopic bladder substitution, which becomes even more apparent over time.

OBJECTIVE: To analyse urinary continence in long-term survivors after radical cystectomy (RC) and orthotopic bladder substitution (OBS) according to attempted nerve-sparing (NS) status. PATIENTS AND METHODS: We analysed 180 consecutive patients treated at our department between 1985 and 2007, who underwent RC with OBS, and survived ≥10 years after RC. We stratified patients by attempted NS status and evaluated continence outcomes using descriptive statistics and Cox proportional hazards regression models. A secondary analysis evaluated erectile function as a quality control for attempted NS. RESULTS: The median (interquartile range [IQR]) age at RC was 62 (57-71) years. Of 180 patients, attempted NS status was none in 24 (13%), unilateral in 100 (56%), and bilateral in 56 (31%). After a median (IQR) follow-up of 169 (147-210) months, 160 (89%) patients were continent during daytime and 124 (69%) during night-time. In multivariable analysis, any degree of attempted NS was significantly associated with daytime continence (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.05-4.11; P = 0.04). Correspondingly, any attempted NS was significantly associated with night-time continence (OR 2.51, 95% CI 1.08-5.85; P = 0.03). Recovery of erectile function at 5 years was also significantly associated with attempted NS (P < 0.001). CONCLUSION: Nerve-sparing during RC and OBS was associated with better long-term continence outcomes. This becomes more apparent as the patients age with their OBS. We advocate a NS RC whenever an OBS is considered.

Does Subclassification of Pathologically Organ Confined (pT2) Prostate Cancer Provide Prognostic Discrimination of Outcomes after Radical Prostatectomy?

PURPOSE: We tested the latest update in the prostate cancer staging system by assessing the prognostic association of pT2 subclassification with the probability of survival related outcomes in patients who underwent radical prostatectomy. MATERIALS AND METHODS: We retrospectively analyzed the records of a total of 15,305 patients who underwent radical prostatectomy at 2 referral centers between 1985 and 2016, and had pT2 disease at the final pathological evaluation. Descriptive statistics were used to compare baseline data stratified by pT2 substages (pT2a/b vs pT2c). Cox regression models were adjusted for institution analyzed differences in the rate of biochemical recurrence, metastasis, cancer specific death and overall mortality. Multivariable Cox regression models were used to evaluate the predictive value of pT2 subclassification for survival, including the linear predictor from the Stephenson nomogram. RESULTS: Prostate specific antigen levels and Gleason score differed significantly between the pT2 substages (each p <0.0001). At a median followup of 6.0 years (IQR 3.3-10.1) 2,083 patients had biochemical recurrence, 161 had metastases, 43 had died of prostate cancer and 1,032 had died of another cause. On univariate analysis the pT2 subclassification was significantly associated with biochemical recurrence (p = 0.001) and distant metastasis (p = 0.033) but not with cancer specific death (p = 0.6) or overall mortality (p = 0.3). Multivariable analysis showed no evidence of a significant association between the pT2 subclassification and biochemical recurrence (p = 0.4) or distant metastasis (p = 0.6). Multivariable analysis of cancer specific death and overall mortality was omitted due to lack of significance on univariate analysis. CONCLUSIONS: Subclassification of pT2 prostate cancer is not a prognostic indicator of survival related outcomes after radical prostatectomy. Our results validate the elimination of pT2 substages in the updated staging system.

More extended lymph node dissection template at radical prostatectomy detects metastases in the common iliac region and in the fossa of Marcille.

OBJECTIVES: To assess the effect of adding lymph nodes (LNs) located along the common iliac vessels and in the fossa of Marcille to the extended pelvic LN dissection (PLND) template at radical prostatectomy (RP). PATIENTS AND METHODS: A total of 485 patients underwent RP and PLND at a referral centre between 2000 and 2008 (historical cohort: classic extended PLND template) and a total of 268 patients between 2010 and 2015 (contemporary cohort: extended PLND template including LNs located along the common iliac vessels and in the fossa of Marcille). Descriptive analyses were used to compare baseline, pathological, complication and functional data between the two cohorts. A logistic regression model was used to assess the template's effect on the probability of detecting LN metastases. RESULTS: Of 80 patients in the historical cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 23 (29%), and the internal iliac in 18 (23%), while 39 patients (49%) had metastases in both locations. Of 72 patients in the contemporary cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 17 patients (24%), the internal iliac in 24 patients (33%), and the common iliac in one patient (1%), while 30 patients (42%) had metastases in >1 location (including fossa of Marcille in five patients). Among all 46 patients in the contemporary cohort with ≤2 metastases, three had one or both metastases in the common iliac region or the fossa of Marcille. The adjusted probability of detecting LN metastases was higher, but not significantly so, in the contemporary cohort. There were no differences between the two cohorts in complication rates and functional outcomes. CONCLUSION: A more extended template detects LN metastases in the common iliac region and the fossa of Marcille and is not associated with a higher risk of complications; however, the overall probability of detecting LN metastases was not significantly higher.

Metastasectomy in older adults with urothelial carcinoma: Population-based analysis of use and outcomes.

BACKGROUND: Metastatic urothelial carcinoma of the bladder, ureter, or renal pelvis is a highly aggressive disease with poor outcomes. Even with platinum-based chemotherapy, the median overall survival is 15 months and the 5-year survival is only 15%. The role of metastasectomy in urothelial carcinoma is currently undefined. OBJECTIVE: To examine the use and outcomes of metastasectomy in older patients with urothelial carcinoma in a large population-based dataset. DESIGN, SETTING, AND PARTICIPANTS: We conducted a SEER-Medicare study, and from 70,648 urothelial carcinoma patients who met inclusion criteria, we identified 497 patients who had at least 1 metastasectomy during a median follow-up of 40 months. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary study endpoints were metastasectomy use, the length of stay for metastasectomy, complications, and overall survival following metastasectomy. Secondary outcomes included 30-day mortality and readmission rate following metastasectomy. RESULTS AND LIMITATIONS: We identified 497 patients meeting inclusion criteria who had at least 1 metastasectomy during the study period including 24 patients who had more than 1 procedure resulting in a total of 523 metastasectomies. The median overall survival after the first metastasectomy was 19 months (95% CI: 15-23; interquartile range: 4-74). In this selected patient population, over a third of patients were alive at 3 years. In the 476 patients who had evaluable discharge dates, the median length of stay after metastasectomy was 7 days (IQR: 4-12), and 10% of patients had at least 1 complication within 30 days of discharge. Thirty-day mortality after metastasectomy was 10% (n = 53/523) and was largely driven by the mortality associated with resections of urothelial cancer brain metastases. CONCLUSIONS: In well-selected patients with urothelial carcinoma with a reasonable life expectancy, resection of metastatic lesions is safe and is associated with long-term survival and potential cures.

Nephrometry scores and perioperative outcomes following robotic partial nephrectomy

ABSTRACT Objectives: Based on imaging features, nephrometry scoring systems have been conceived to create a standardized and reproducible way to characterize renal tumor anatomy. However, less is known about which of these individual measures are important with regard to clinically relevant perioperative outcomes such as ischemia time (IT), estimated blood loss (EBL), length of hospital stay (LOS), and change in estimated glomerular filtration rate (eGFR) after robotic partial nephrectomy (PN). We aimed to assess the utility of the RENAL and PADUA scores, their subscales, and C-index for predicting these outcomes. Materials and Methods: We analyzed imaging studies from 283 patients who underwent robotic PN between 2008 and 2014 to assign nephrometry scores (NS): PADUA, RENAL and C-index. Univariate linear regression was used to assess whether the NS or any of their subscales were associated with EBL or IT. Multivariable linear regression and linear regression models were created to assess LOS and eGFR. Results: The three NS were significantly associated with EBL, IT, LOS, and eGFR at 12 months after surgery. All subscales with the exception of anterior/posterior were significantly associated with EBL and IT. Collecting system, renal rim location, renal sinus, exophytic/endophytic, and nearness to collecting system were significant predictors for LOS. Only renal rim location, renal sinus invasion and polar location were significantly associated with eGFR at 12 months. Conclusions: Tumor size and depth are important characteristics for predicting robotic PN outcomes and thus could be used individually as a simplified way to report tumors features for research and patient counseling purposes.

Nephrometry scores and perioperative outcomes following robotic partial nephrectomy.

OBJECTIVES: Based on imaging features, nephrometry scoring systems have been conceived to create a standardized and reproducible way to characterize renal tumor anatomy. However, less is known about which of these individual measures are important with regard to clinically relevant perioperative outcomes such as ischemia time (IT), estimated blood loss (EBL), length of hospital stay (LOS), and change in estimated glomerular filtration rate (eGFR) after robotic partial nephrectomy (PN). We aimed to assess the utility of the RENAL and PADUA scores, their subscales, and C-index for predicting these outcomes. MATERIALS AND METHODS: We analyzed imaging studies from 283 patients who underwent robotic PN between 2008 and 2014 to assign nephrometry scores (NS): PADUA, RENAL and C-index. Univariate linear regression was used to assess whether the NS or any of their subscales were associated with EBL or IT. Multivariable linear regression and linear regression models were created to assess LOS and eGFR. RESULTS: The three NS were significantly associated with EBL, IT, LOS, and eGFR at 12 months after surgery. All subscales with the exception of anterior/posterior were significantly associated with EBL and IT. Collecting system, renal rim location, renal sinus, exophytic/endophytic, and nearness to collecting system were significant predictors for LOS. Only renal rim location, renal sinus invasion and polar location were significantly associated with eGFR at 12 months. CONCLUSIONS: Tumor size and depth are important characteristics for predicting robotic PN outcomes and thus could be used individually as a simplified way to report tumors features for research and patient counseling purposes.

Contemporary update on neoadjuvant therapy for bladder cancer.

Administration of neoadjuvant chemotherapy preceding radical cystectomy in patients with bladder cancer remains a matter of debate. Results of prospective, randomized studies have demonstrated an overall absolute survival benefit of 5% at 5 years, provided cisplatin-based combination regimens are used. Owing to the perception of a modest survival benefit, the medical community has been slow to adopt the use of neoadjuvant chemotherapy. Other reasons for the underuse of neoadjuvant chemotherapy range from patient ineligibility to fear of delaying potentially curative surgery in nonresponders. Instead, several institutions have adopted an individualized, risk-adapted approach, in which the decision to administer chemotherapy is based on clinical stage and patient comorbidity profile. The development of new cytotoxic and targeted therapies, in particular immune checkpoint inhibitors, warrants well-designed prospective studies to test their efficacy alone or in combination in the neoadjuvant setting. Moving forward, genomic characterization of muscle-invasive bladder cancer could offer information that aids clinicians in selecting the appropriate chemotherapy regimen. Following neoadjuvant therapy, every effort should be made to ensure optimal surgery, as surgical margins and the number of removed lymph nodes are prognostic factors; thus, radical cystectomy and a meticulous extended pelvic lymph node dissection should be performed by expert surgeons.

Racial Variation in the Utility of Urinary Biomarkers PCA3 and T2ERG in a Large Multicenter Study.

PURPOSE: To our knowledge it is unknown whether urinary biomarkers for prostate cancer have added utility to clinical risk calculators in different racial groups. We examined the utility of urinary biomarkers added to clinical risk calculators for predicting prostate cancer in African American and nonAfrican American men. MATERIALS AND METHODS: Demographics, PCPT (Prostate Cancer Prevention Trial) risk scores, data on the biomarkers data PCA3 (prostate cancer antigen 3) and T2ERG (transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog gene fusion), and biopsy pathology features were prospectively collected on 718 men as part of EDRN (Early Detection Research Network). Utility was determined by generating ROC curves and comparing AUC values for the baseline multivariable PCPT model and for models containing biomarker scores. RESULTS: PCA3 and T2ERG added utility for the prediction of prostate cancer and clinically significant prostate cancer when combined with the PCPT Risk Calculator. This utility was seen in nonAfrican American men only for PCA3 (AUC 0.64 increased to 0.75 for prostate cancer and to 0.69-0.77 for clinically significant prostate cancer, both p <0.001) and for T2ERG (AUC 0.64-0.74 for prostate cancer, p <0.001, and 0.69-0.73 for clinically significant prostate cancer, p = 0.029). African American men did not have an added benefit with the addition of biomarkers, including PCA3 (AUC 0.75-0.77, p = 0.64, and 0.65-0.66, p = 0.74) and T2ERG (AUC 0.75-0.74, p = 0.74, and 0.65-0.64, p = 0.88), for prostate cancer and clinically significant prostate cancer, respectively. Limitations include the small number of African American men (72). The post hoc subgroup analysis nature of the study limited findings to being hypothesis generating. CONCLUSIONS: As novel biomarkers are discovered, clinical utility should be established across demographically diverse cohorts.

Association of Aromatase With Bladder Cancer Stage and Long-Term Survival: New Insights Into the Hormonal Paradigm in Bladder Cancer.

BACKGROUND: Hormonal factors may play a role in bladder cancer (BCa). We investigated the expression of aromatase and estrogen receptor (ER)ß and its association with pathological variables and survival outcomes. PATIENTS AND METHODS: BCa specimens from 40 patients were evaluated. Immunohistochemistry was performed for aromatase and ERß. Descriptive statistics and univariate analyses assessed the association of these markers with pathologic variables and survival outcomes. RESULTS: Aromatase expression was significantly associated with tumor stage; muscle-invasive disease was found in 15 of 19 (79%) patients with positive staining and in 7 of 18 (39%) patients with negative staining (P = .02). Node-positive disease was found in 8 of 19 (42%) patients with positive staining and 1 of 18 (6%) patients with negative staining (P = .01). After a median follow-up of 112 months, Cox regression analysis demonstrated that aromatase expression was associated with a more than 2-fold risk of cancer recurrence (hazard ratio, 2.37; confidence interval, 0.92-6.08; P = .07) and an almost 4-fold higher risk of cancer-specific death (hazard ratio, 3.66; 95% confidence interval, 1.19-12.06; P = .02). Muscle-invasive disease was found in 15 of 18 (83%) ERß-positive specimens and 4 of 12 (33%) ERß-negative specimens (P = .0009). Hierarchical clustering analysis demonstrated a 4-fold up-regulation of ERß gene expression in tumor versus adjacent, non-tumor urothelium (P < .05). However, no significant association with survival outcomes was found. CONCLUSION: Aromatase expression in BCa may be associated with advanced tumor stage and poorer survival outcomes. ERß is upregulated in malignant tissue, and its expression is associated with muscle-invasive disease. These findings provide further evidence for the hormonal paradigm in BCa.

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 impact of socioeconomic status on perioperative complications and oncologic outcomes in patients undergoing radical cystectomy.

PURPOSE: To examine if patients of lower socioeconomic status (SES) are at higher risk of perioperative complications and experience different oncologic outcomes after radical cystectomy (RC). METHODS: Retrospective review was performed on 383 consecutive non-metastatic patients who underwent definitive RC at a tertiary referral center. Along with clinical and pathologic parameters traditionally utilized for risk stratification, potential social determinants of health were estimated using US Census data. Zip code-derived proxies of SES included median annual household income and percentage of residents completing high school education. Patients were grouped based on SES parameters, and potential differences were assessed. Multivariable logistic regression was then performed to identify predictors of complication within 90 days of RC. Survival outcomes were plotted using Kaplan-Meier survival curves. RESULTS: Overall, 167 (46.2%) patients suffered any complication within 90 days of RC. On multivariable analysis, length of stay (p ≤ 0.001), lower income grouping (p = 0.03), and lowest education tertile (p = 0.007) were significant predictors of any complication. Income (p = 0.04) and education (p = 0.008) groupings remained significant predictors in a subset analysis looking specifically at post-discharge complications. No significant differences in recurrence-free or overall survival estimates were observed among education (log-rank test: p > 0.9 and p = 0.6, respectively) or income (log-rank test: p = 0.2 and p = 0.09, respectively) groupings. CONCLUSION: Patients of lower socioeconomic status who undergo RC for bladder cancer are at increased risk of perioperative complications. Further studies are needed to clarify this relationship, and to explore interventions aimed to improve outcomes.

Induction of PSMA and Internalization of an Anti-PSMA mAb in the Vascular Compartment.

Angiogenesis is critical for tumor growth and survival and involves interactions between cancer and endothelial cells. Prostate-specific membrane antigen (PSMA/FOLH1) is expressed in the neovasculature of several types of cancer. However, the study of neovascular PSMA expression has been impeded as human umbilical vein endothelial cell (HUVEC) cultures are PSMA-negative and both tumor xenografts and patient-derived xenograft (PDX) models are not known to express PSMA in their vasculature. Therefore, PSMA expression was examined in HUVECs, in vitro and in vivo, and we tested the hypothesis that cancer cell-HUVEC crosstalk could induce the expression of PSMA in HUVECs. Interestingly, conditioned media from several cancer cell lines induced PSMA expression in HUVECs, in vitro, and these lines induced PSMA, in vivo, in a HUVEC coimplantation mouse model. Furthermore, HUVECs in which PSMA expression was induced were able to internalize J591, a mAb that recognizes an extracellular epitope of PSMA as well as nanoparticles bearing a PSMA-binding ligand/inhibitor. These findings offer new avenues to study the molecular mechanism responsible for tumor cell induction of PSMA in neovasculature as well as the biological role of PSMA in neovasculature. Finally, these data suggest that PSMA-targeted therapies could synergize with antiangiogenic and/or other antitumor agents and provide a promising model system to test therapeutic modalities that target PSMA in these settings. IMPLICATIONS: Cancer cells are able to induce PSMA expression in HUVECs, in vitro and in vivo, allowing internalization of PSMA-specific mAbs and nanoparticles bearing a PSMA-binding ligand/inhibitor. Mol Cancer Res; 14(11); 1045-53. ©2016 AACR.