Surgical Approach Does Not Impact Margin Status After Partial Nephrectomy for Large Renal Masses.

PURPOSE: While surgical approach has recently been associated with positive surgical margin (PSM) after partial nephrectomy (PN) for small (<4 cm) renal masses, its impact on margin status for large (>4 cm) masses is unclear. We sought to evaluate the relationship between margin and surgical approach in patients undergoing PN for large renal masses. MATERIALS AND METHODS: Using the National Cancer Database (NCDB), we identified patients undergoing PN for pathological T1b and T2a renal-cell carcinoma diagnosed from 2010 to 2013. Conversions to open surgery were also included in our analysis. The primary outcome was surgical margin status. Multivariable regression modeling was performed to identify factors associated with PSM. A propensity score matching analysis was then performed to evaluate the impact of margin status on overall survival (OS). RESULTS: Of the 7495 patients undergoing PN for pT1b and pT2a renal masses over the study period, 504 (6.7%) had PSM. On multivariable analysis, surgical approach (laparoscopic or robot assisted vs open) was not significantly associated with surgical margin (p = 0.12 and p = 0.44, respectively). Tumor stage (T2a vs T1b) also showed no significant association (p = 0.18). A subsequent multivariable analysis using clinical staging showed that surgical approach (p = 0.28 and p = 0.54, respectively), tumor stage (p = 0.78), and conversion-to-open surgery (p = 0.98) had no significant association with PSM. Propensity score matched analysis showed that PSM was not significantly associated with OS (hazard ratio 0.95 [95% confidence interval 0.47-1.92] p = 0.88). CONCLUSION: In a contemporary nation-wide cohort, surgical approach was not associated with an increased risk of PSM for large, noninvasive renal masses. Furthermore, increased size from T1b to T2a was not associated with an increased risk of PSM. These data suggest that surgical approach should be selected by surgeon comfort level with an individual tumor, rather than the size of the tumor itself.

Gynecologic Organ Involvement During Radical Cystectomy for Bladder Cancer: Is It Time to Routinely Spare the Ovaries?

PURPOSE: To determine a subset of women who could undergo ovary-sparing radical cystectomy (OSRC) for bladder cancer without compromising oncologic safety. PATIENTS AND METHODS: A retrospective review was performed of 164 consecutive women who underwent cystectomy at a single tertiary-care center from 1997 to 2018. Clinicopathologic and preoperative radiographic data were reviewed. Univariable and multivariable logistic regression models adjusting for pathologic stage, lymphovascular invasion (LVI), and carcinomain-situ were performed to evaluate the risk of ovarian and reproductive organ (RO) involvement. RESULTS: A total of 123 women with a median age of 71 years underwent radical cystectomy (RC) with removal of ROs for primary bladder cancer. Nineteen women (15%) had RO involvement by bladder cancer, and 5 of them (4%) were specifically found to have ovarian involvement. Patients with ovarian involvement of bladder cancer had more locally advanced disease (P = .01), LVI (P = .003) and positive margins (P = .003). On multivariable logistic regression, ≥ pT3 (odds ratio = 10.2; 95% confidence interval, 2.0-51.6; P = .005) and LVI (odds ratio = 3.9; 95% confidence interval, 1.1-14.2; P = .037) were associated with increased risk of RO involvement. Among 15 patients excluded for having a nonbladder primary malignancy, a third had RO involvement, and 2 (13%) had ovarian metastases. No women in our cohort had a primary ovarian malignancy detected at the time of RC. CONCLUSION: Women with ovarian involvement by malignancy at the time of RC either had locally advanced disease with LVI or a non-bladder primary malignancy. The risk of incompletely resecting the primary malignancy would be rare if OSRC was performed on women with organ-confined (≤T2) urothelial carcinoma.

Urinary pH and the risk of recurrence in patients with non-muscle invasive bladder cancer.

INTRODUCTION: To evaluate the effect of urine pH on tumor recurrence rates in patients undergoing surveillance after initial diagnosis of non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: All patients diagnosed with NMIBC at a tertiary referral center from January 2004 to March 2015 were reviewed. Our primary outcome was time to first recurrence after transurethral resection of bladder tumor (TURBT). Patients were analyzed according to the average urine pH of all urinalysis data over the surveillance period from TURBT to first recurrence. Kaplan-Meier survival analysis was used to determine differences in median time to recurrence. Cox proportional hazards regression was used to assess independent predictors of cancer recurrence. RESULTS: A total of 252 patients were included, of which 155 patients had average pH ≤ 6 (median pH 5.5) and 97 patients had average pH > 6 (median pH 6.8), p < 0.001. There was no significant difference in median time to recurrence between low/acidic pH (≤ 6) and high/basic pH (> 6) groups (28 months versus 17 months, respectively, p = 0.3444). Similarly, urine pH did not affect the risk of recurrence in a subgroup analysis stratified by smoking status. On multivariable Cox regression analysis, there was no association between average pH and recurrence among high grade tumors (HR = 1.33, 95% CI = 0.76 to 2.34, p = 0.3186), or low grade tumors (HR = 1.013, 95% CI = 1.01 to 1.58, p = 0.96). CONCLUSIONS: There was no association between urine pH and risk of tumor recurrence, regardless of smoking status. These findings suggest that modification of urine pH is unlikely to decrease the frequency of tumor recurrence in patients with NMIBC.

The Role of Gut Microbiome in the Pathogenesis of Prostate Cancer: A Prospective, Pilot Study.

OBJECTIVE: To elucidate potential biomarkers or mechanistic principles involved with the gut microbiota and its impact on prostate cancer pathogenesis. MATERIALS AND METHODS: We performed a prospective case-control pilot study evaluating the gut microbiome of 20 men with either benign prostatic conditions (n = 8) or intermediate or high risk clinically localized prostate cancer (Gleason ≥4 + 3 cN0M0) (n = 12) undergoing care at tertiary referral center from September 1, 2015 to March 1, 2016. Key exclusion criteria included recent antibiotic use, significant gastrointestinal disorders, hormonal or systemic therapy for prostate cancer. Computational genomics analysis was performed on collected stool samples using MetaPhlAn2 and HUMAnN2 platforms. Linear discriminant analysis effect size method was used to support high-dimensional class comparisons to find biologically relevant features. Kruskal-Wallis sum-rank test was used to detect features with significant differential abundance with respect to class, with biological consistency investigated using a set of pairwise tests among subclasses using the Wilcoxon rank-sum test, both to an α ≤0.05. RESULTS: Higher relative abundance of Bacteriodes massiliensis was seen in prostate cancer cases compared to controls. Faecalibacterium prausnitzii and Eubacterium rectalie had higher relative abundance among controls. Biologically significant differences were also found in relative gene, pathway, and enzyme abundance. CONCLUSION: Biologically significant differences exist in the gut microbial composition of men with prostate cancer compared to benign controls. These differences may play a role in the pathobiology of prostate cancer, and warrant further exploration.

Minimally invasive vs open nephrectomy in the modern era: does approach matter?

PURPOSE: To evaluate if the widespread adoption of a minimally invasive approach to radical nephrectomy has affected short- and long-term patient outcomes in the modern era. METHODS: A retrospective cohort study of patients who underwent radical nephrectomy from 2001 to 2012 was conducted using the US National Cancer Institute Surveillance Epidemiology and End Results (SEER) Program and Medicare insurance program database. Patients who underwent open surgery were compared to those who underwent minimally invasive surgery using propensity score matching. RESULTS: 10,739 (85.9%) underwent open surgery and 1776 (14.1%) underwent minimally invasive surgery. Minimally invasive surgery increased from 18.4% from 2001-2004 to 43.5% from 2009 to 2012. After median follow-up of 57.1 months, minimally invasive radical nephrectomy conferred long-term oncologic efficacy in terms of overall (HR 0.84; 95% CI 0.75-0.95) survival and cancer-specific (HR 0.68; 95% CI 0.54-0.86) survival compared to open radical nephrectomy. Minimally invasive surgery was associated with lower risk of inpatient death [risk ratio (RR) 0.45 with 95% CI: (0.20-0.99), p = 0.04], deep vein thrombosis [RR: 0.35 (0.18-0.69), p = 0.002], respiratory complications [RR: 0.73 (0.60-0.89), p = 0.001], infectious complications [RR: 0.35 (0.14-0.90), p = 0.02], acute kidney injury [RR: 0.66 (0.52-0.84), p < 0.001], sepsis [RR: 0.55 (0.31-0.98), p = 0.04], prolonged length of stay (18.6 vs 30.0%, p < 0.001), and ICU admission (19.7 vs 26.3%, p < 0.001). Costs were similar between the two approaches (30-day costs $15,882 vs $15,564; p = 0.70). CONCLUSION: After widespread adoption of minimally invasive approaches to radical nephrectomy across the United States, oncologic standards remain preserved with improved perioperative outcomes at no additional cost burden.

Co-clinical Analysis of a Genetically Engineered Mouse Model and Human Prostate Cancer Reveals Significance of NKX3.1 Expression for Response to 5α-reductase Inhibition.

BACKGROUND: Although men on active surveillance for prostate cancer (PCa) may benefit from intervention with 5α-reductase inhibitors (5-ARIs), it has not been resolved whether 5-ARIs are effective for delaying disease progression and, if so, whether specific patients are more likely to benefit. OBJECTIVE: To identify molecular features predictive of patient response to 5-ARIs. DESIGN, SETTING, AND PARTICIPANTS: Nkx3.1 mutant mice, a model of early-stage PCa, were treated with the 5-ARI finasteride, and histopathological and molecular analyses were performed. Cross-species computational analyses were used to compare expression profiles for treated mice with those of patients who had received 5-ARIs before prostatectomy. INTERVENTION: Finasteride administered to Nkx3.1 mutant mice. 5-ARI-treated patient specimens obtained retrospectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Endpoints in mice included histopathology, immunohistochemistry, and molecular profiling. GraphPad Prism software, R-studio, and Matlab were used for statistical and data analyses. RESULTS AND LIMITATIONS: Finasteride treatment of Nkx3.1 mutant mice resulted in a significant reduction in prostatic intraepithelial neoplasia (PIN), as evident from histopathological and expression profiling analyses. Cross-species computational analysis comparing finasteride-treated mice with two independent 5-ARI-treated patient cohorts showed that reduced NKX3.1 expression is predictive of response to 5-ARI. A limitation of the study is that these retrospective human cohorts have relatively few patients with limited clinical outcome data. Future prospective clinical trials are needed to validate whether stratifying patients on the basis of NKX3.1 expression improves the benefit of 5-ARIs during active surveillance. CONCLUSIONS: This co-clinical study implicates NKX3.1 status as a predictor of response to 5-ARIs, and suggests that molecular features, including NKX3.1 expression, may help to identify PCa patients most likely to benefit from 5-ARIs during active surveillance. PATIENT SUMMARY: The aim of precision cancer prevention is to tailor interventions on the basis of individualized patient characteristics. We propose that patients with low NKX3.1 expression are optimal candidates for intervention with 5α-reductase inhibitors as an adjunct to active surveillance.

Robot-assisted partial cystectomy: perioperative outcomes and early oncological efficacy.

OBJECTIVE: To report on patients undergoing robot-assisted partial cystectomy (RAPC), focusing on perioperative outcomes over a range of clinical, anatomical and pathological variables, as well as the overall oncological efficacy of this approach. PATIENTS AND METHODS: We retrospectively reviewed all patients who underwent RAPC by a single surgeon between 2005 and 2015. We identified 29 patients who underwent surgery for definitive management of a primary bladder tumour. Clinicopathological data and perioperative variables were recorded. Continuous variables were compared using the Student's t-test. Prediction of perioperative outcomes for those undergoing RAPC for intra-diverticular neoplasms was done using univariate logistic regression. Survival was estimated using the Kaplan-Meier method. RESULTS: The median (interquartile range) patient age was 75 (65-81) years, 18 patients (62.1%) had an American Society of Anesthesiologists classification of ≥3, and 10 patients (34.5%) had a history of prior abdominal surgery. The median estimated blood loss (EBL) was 50 mL and the median length of stay (LOS) was 1 day. Two patients (6.9%) had a perioperative complication and five (17.9%) a post-discharge complication at ≤90 days, all of which were minor. The positive surgical margin rate was 3.6% and in those with muscle-invasive disease a median of 12 lymph nodes were removed. Neither the size of diverticulum nor the need for ureteric re-implantation was predictive of LOS, EBL, or complication (P > 0.05). We did not encounter any wound, port site, or unusual recurrence patterns to suggest the technical factors of a robotic approach influenced oncological outcomes. The 5-year overall and recurrence-free survival rates were 79% and 68%, respectively. CONCLUSION: RAPC confers the ability to achieve favourable outcomes with low morbidity and reduced hospital stays. Oncological efficacy compares favourably with the published literature. For experienced surgeons, this may represent the optimal surgical approach for organ-preserving bladder surgery.

Prostate size, nocturia and the digital rectal examination: a cohort study of 30 500 men.

OBJECTIVES: To evaluate the utility of the digital rectal examination (DRE) in estimating prostate size and the association of DRE with nocturia in a population-based cohort. SUBJECTS AND METHODS: We identified all men randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial for whom DRE results were available. Men were excluded if they had a history of prostate surgery or incident prostate cancer. Prostate posterior surface area was derived from DRE sagittal and transverse estimates. Relationships between prostate posterior surface area, transrectal ultrasonography (TRUS), prostate-specific antigen (PSA) and nocturia were analysed using intraclass correlation coefficients (ICCs), Spearman's rank correlation and multivariable logistic regression. RESULTS: A total of 30 500 men met the inclusion criteria, with 103 275 screening visits containing paired DRE and PSA data. Digital rectal examination posterior surface area estimates had an ICC of 0.547 (95% CI 0.541-0.554) and were significantly yet modestly correlated with elevated PSA level (rs = 0.18, P < 0.001) and TRUS prostate volume (rs = 0.32, P < 0.001). Prostate posterior surface area was significantly associated with nocturia on multivariable analysis, but was not significant in stratified analysis of men with cardiovascular risk factors (hypertension, diabetes, high body mass index, stroke). In men without these risk factors, the highest quintile of DRE posterior surface area had 22% greater odds of nocturia than the lowest quintile (odds ratio 1.216, 95% CI 1.036-1.427). CONCLUSIONS: Digital rectal examination is a modestly accurate tool for measuring prostate volume. While DRE posterior surface area represents a statistically significant predictor of nocturia, the magnitude of effect suggests it has limited clinical utility for assessing this condition, particularly in the presence of cardiovascular risk factors.

Prognostic Significance of a Negative Prostate Biopsy: An Analysis of Subjects Enrolled in a Prostate Cancer Screening Trial.

PURPOSE: To our knowledge the optimal treatment of patients following a negative prostate biopsy is unknown. Consequently, resources are increasingly being directed toward risk stratification in this cohort. However, the risk of prostate cancer mortality in this group before the introduction of supplemental biomarkers and imaging techniques is unclear. MATERIALS AND METHODS: The PLCO (Prostate, Lung, Colorectal and Ovarian Cancer) Screening Trial provides survival data prior to the implementation of new diagnostic interventions. We divided men with an initial positive screen and a subsequent prostate biopsy into cohorts based on positive or negative results. Prostate cancer specific mortality was then compared to that in the trial control arm to estimate the prognostic significance of biopsy results relative to the general population. RESULTS: A total of 36,525 and 36,560 patients comprised the screening and control arms, respectively. Of 4,064 subjects with a positive first screen 1,233 underwent a linked biopsy, of which 473 were positive and 760 were negative. At a median followup of 12.9 years, 1.1% of men in the negative biopsy cohort had died of prostate cancer. The difference in mortality rates between the negative biopsy and control arms was 0.734 deaths per 1,000 person-years. The proportional subhazard ratios of prostate cancer specific mortality for negative biopsy and positive biopsy relative to the control arm were 2.93 (95% CI 1.44-5.99) and 18.77 (95% CI 12.62-27.93), respectively. CONCLUSIONS: After a negative prostate biopsy, men face a relatively low risk of death from prostate cancer when followed with traditional markers and biopsy techniques. This suggests limited potential for new diagnostic interventions to improve survival in this group.

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.

Adoption of Technology and Its Impact on Nephrectomy Outcomes, a U.S. Population-Based Analysis (2008-2012).

PURPOSE: Robot-assisted surgery has been touted as offering superior outcomes in various oncologic surgeries. We sought to evaluate the comparative effectiveness of robotic radical nephrectomy (RRN) compared with laparoscopic radical nephrectomy (LRN) in regard to hospital charges, complications, and survival. MATERIALS AND METHODS: Using the Surveillance Epidemiology and End Results (SEER) Program-Medicare linked database, we identified patients over the age of 65 who underwent radical nephrectomy (RN) for nonmetastatic renal-cell carcinoma from 2008 to 2012. Patients who underwent RRN were compared with those who underwent LRN. We used propensity scoring matching to compare perioperative and survival outcomes, including overall survival, cancer-specific survival, major adverse events, and healthcare charges. RESULTS: Two hundred forty-one patients underwent RRN, and 574 patients underwent LRN. After propensity score matching, the adverse events rate and length of stay were similar between two groups (Major Events: 5.7% vs 6.1%, p = 0.84; prolonged LOS: 17.8% vs 16.1%, p = 0.62). The inpatient charges following RRN were significantly higher than those of LRN ($53,681 vs $44,161, p < 0.01). The mean follow-up of the cohort was 3.2 years. Estimated overall survival (88.0% vs 87.9%, p = 0.90) and cancer-specific survival (98.1% vs 96.4%, p = 0.25) were similar between the two matched cohorts at 3 years. CONCLUSION: The robotic platform showed no benefit over standard laparoscopy for RN, as we found no difference in oncologic efficacy or adverse event rates.

Factors Impacting the Occurrence of Local, Distant and Atypical Recurrences after Robot-Assisted Radical Cystectomy: A Detailed Analysis of 310 Patients.

PURPOSE: Peritoneal carcinomatosis and extrapelvic lymph node metastases can be seen following robot-assisted radical cystectomy. In an attempt to identify predictors of these atypical metastases we report a detailed analysis of patients treated with robot-assisted radical cystectomy in whom recurrences developed. MATERIALS AND METHODS: A total of 310 patients underwent robot-assisted radical cystectomy for bladder cancer from 2001 to 2015. Descriptive statistics were used to compare baseline variables between patients without recurrence and those with local, distant or atypical recurrence. Univariate and multivariable regression models were used to assess the effect of variables on oncologic outcomes including recurrence location. RESULTS: At a median followup of 24 months (IQR 14-51) 81 patients had recurrence. On multivariable analysis tumor classification, lymphovascular invasion, estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 and perioperative blood transfusion were significantly associated with any recurrence. Specific analyses showed that tumor and nodal classification, lymphovascular invasion and positive surgical margins were associated with all 3 recurrence locations (all p <0.05). Previous abdominal surgery was protective against atypical recurrences (HR 0.36, 95% CI 0.13-0.95, p = 0.04). Estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 and perioperative blood transfusion conferred a higher risk of distant or atypical recurrence but not of local recurrence (all p <0.05). Operative time and previous pelvic radiotherapy were not associated with any recurrence locations. CONCLUSIONS: Predictors of distant recurrences, peritoneal carcinomatosis and extrapelvic lymph node metastases after robot-assisted radical cystectomy did not significantly differ and were mainly dictated by pathological tumor characteristics. Results suggest that the risk of atypical recurrence is chiefly influenced by tumor biology rather than surgical aspects.