To elucidate potential biomarkers or mechanistic principles involved with the gut microbiota and its impact on prostate cancer pathogenesis.
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.
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.
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.
Purpose Urothelial carcinoma of the bladder is the 4th most common malignancy in men and the 8th most common cause of male cancer death in the United States. Conversely, upper tract urothelial ...carcinoma accounts for only 5% to 10% of all urothelial carcinoma. Due to the relative preponderance of urothelial carcinoma of the bladder, much of the clinical decision making regarding upper tract urothelial carcinoma is extrapolated from evidence that is based on urothelial carcinoma of the bladder cohorts. In fact, only 1 major urological organization has treatment guidelines specific for upper tract urothelial carcinoma. While significant similarities exist between these 2 diseases, ignoring the important differences may be preventing us from optimizing therapy in patients with upper tract urothelial carcinoma. Therefore, we explored these dissimilarities, including the differential importance of gender, anatomy, staging, intracavitary therapy, surgical lymphadenectomy and perioperative systemic chemotherapy on the behavior of urothelial carcinoma of the bladder and upper tract urothelial carcinoma. Materials and Methods A nonsystematic literature search using the MEDLINE/PubMed® database was conducted to identify original articles, review articles and editorials. Searches were limited to the English language and studies in humans and in adults, and used the key words urothelial carcinoma, upper tract urothelial carcinoma or transitional cell carcinoma combined with several different sets of key words to identify appropriate publications for each section of the manuscript. The key words, broken down by section, were 1) epidemiology, sex, gender; 2) location, tumor location; 3) staging, stage; 4) intracavitary, intravesical, topical therapy; 5) lymphadenectomy, lymph node, lymph node dissection and 6) adjuvant, neoadjuvant, chemotherapy. Results Women who present with urothelial carcinoma of the bladder do so with less favorable tumor characteristics and have worse survival than men. However, gender does not appear to be associated with survival outcomes in upper tract urothelial carcinoma. The prognostic effect that urothelial carcinoma tumor location has on outcomes prediction is a matter of debate, and the influence of tumor location may reflect our technical ability to accurately stage and treat the disease more than the actual tumor biology. Moreover, technical limitations of upper tract urothelial carcinoma sampling compared to transurethral resection for urothelial carcinoma of the bladder are the most important source of staging differences between the 2 diseases. Intravesical chemotherapy and immunotherapy are essential components of standard of care for most nonmuscle invasive bladder cancer, while adjuvant intracavitary therapy for patients with upper tract urothelial carcinoma treated endoscopically or percutaneously has been sparsely used and without any clear guidelines. The widespread adoption of the use of intracavitary therapy in the upper tract will likely not only require additional data to support its efficacy, but will also require a less cumbersome means of administration. Lymphadenectomy at the time of radical cystectomy is widely accepted while lymphadenectomy at the time of radical nephroureterectomy is performed largely at the discretion of the surgeon. Among other reasons, this may be due in part to the variable lymphatic drainage along the course of the ureter compared to the relatively confined lymphatic landing sites for the bladder. Level I evidence has demonstrated a clear survival benefit for systemic chemotherapy before radical surgery or radiation in patients with clinical T2-4N0M0 urothelial carcinoma of the bladder. Such data are not available in the population with upper tract urothelial carcinoma. However, the use of neoadjuvant chemotherapy may be even more important in upper tract urothelial carcinoma than in urothelial carcinoma of the bladder because of the obligatory kidney function loss that occurs at radical nephroureterectomy. Conclusions While urothelial carcinoma of the bladder and upper tract urothelial carcinoma share many characteristics, they represent 2 distinct diseases. There are practical, anatomical, biological and molecular differences that warrant consideration when risk stratifying and treating patients with these disparate twin diseases. To overcome the challenges that impede progress toward evidence-based medicine in upper tract urothelial carcinoma, we believe that focused collaborative efforts will best augment our understanding of this rare disease and ultimately improve the care we deliver to our patients.
Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis ...of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.
Abstract Background Concerns remain whether robot-assisted radical cystectomy (RARC) compromises survival because of inadequate oncologic resection or alteration of recurrence patterns. Objective To ...describe recurrence patterns following open radical cystectomy (ORC) and RARC. Design, setting, and participants Retrospective review of 383 consecutive patients who underwent ORC ( n = 120) or RARC ( n = 263) at an academic institution from July 2001 to February 2014. Intervention ORC and RARC. Outcome measurements and statistical analysis Recurrence-free survival estimates were illustrated using the Kaplan-Meier method. Recurrence patterns (local vs distant and anatomic locations) within 2 yr of surgery were tabulated. Cox regression models were built to evaluate the effect of surgical technique on the risk of recurrence. Results and limitations The median follow-up time for patients without recurrence was 30 mo (interquartile range IQR 5–72) for ORC and 23 mo (IQR 9–48) for RARC ( p = 0.6). Within 2 yr of surgery, there was no large difference in the number of local recurrences between ORC and RARC patients (15/65 23% vs 24/136 18%), and the distribution of local recurrences was similar between the two groups. Similarly, the number of distant recurrences did not differ between the groups (26/73 36% vs 43/147 29%). However, there were distinct patterns of distant recurrence. Extrapelvic lymph node locations were more frequent for RARC than ORC (10/43 23% vs 4/26 15%). Furthermore, peritoneal carcinomatosis was found in 9/43 (21%) RARC patients compared to 2/26 (8%) ORC patients. In multivariable analyses, RARC was not a predictor of recurrence. Limitations of the study include selection bias and a limited sample size. Conclusions Within limitations, we found that RARC is not an independent predictor of recurrence after surgery. Interestingly, extrapelvic lymph node locations and peritoneal carcinomatosis were more frequent in RARC than in ORC patients. Further validation is warranted to better understand the oncologic implications of RARC. Patient summary In this study, the locations of bladder cancer recurrences following conventional and robotic techniques for removal of the bladder are described. Although the numbers are small, the results show that the distribution of distant recurrences differs between the two techniques.
Abstract Background Radical cystectomy is the gold-standard management for muscle-invasive bladder cancer, and there is debate concerning the comparative effectiveness of robotic-assisted (RARC) ...versus open radical cystectomy (ORC). Objective To compare utilization, perioperative, cost, and survival outcomes of RARC versus ORC. Design, setting, and participants We identified bladder urothelial carcinoma treated with RARC ( n = 439) or ORC ( n = 7308) during 2002–2012 using the Surveillance, Epidemiology, and End Results Program-Medicare linked data. Intervention Comparison of RARC versus ORC. Outcome measurements and statistical analysis We used propensity score matching to compare perioperative and survival outcomes, including lymph node yield, perioperative complications, and healthcare costs. Results and limitations Utilization of RARC increased from 0.7% of radical cystectomies in 2002 to 18.5% in 2012 ( p < 0.001). Women comprised 13.9% versus 18.1% ( p = 0.007) of RARC versus ORC, respectively. RARC was associated with greater lymph node yield with 41.5% versus 34.9% having ≥10 lymph nodes removed (relative risk 1.1, 95% confidence interval CI 1.01–1.22, p = 0.03) and shorter mean length of hospitalization at 10.1 (± standard deviation 7.1) d versus 11.2 (± 8.6) d ( p = 0.004). While inpatient costs were similar, RARC was associated with increased home healthcare utilization (relative risk 1.14, 95% CI 1.04–1.26, p = 0.009) and higher 30-d ( p < 0.01) and 90-d ( p < 0.01) costs. With a median follow-up of 44 mo (interquartile range 16–78), overall survival (hazard ratio 0.88, 95% CI 0.74–1.05) and cancer-specific survival (hazard ratio 0.91, 95% CI 0.66–1.26) were similar. Conclusions RARC provides equivalent perioperative and intermediate term outcomes to ORC. Additional long-term and randomized studies are needed for continued comparative effectiveness assessment of RARC versus ORC. Patient summary Our population-based US study demonstrates that robotic-assisted radical cystectomy has similar perioperative and survival outcomes albeit at higher costs.
Abstract Background There is a lack of consensus regarding the optimal approach to the bladder cuff during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Objectives To ...compare the oncologic outcomes following RNU using three different methods of bladder cuff management. Design, setting, and participants Retrospective analysis of 2681 patients treated with RNU for UTUC at 24 international institutions from 1987 to 2007. Intervention Three methods of bladder cuff excision were performed: transvesical, extravesical, and endoscopic. Outcome measurements and statistical analysis Univariable and multivariable models tested the effect of distal ureter management on intravesical recurrence, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results and limitations Of the 2681 patients, 1811 (67.5%) underwent the transvesical approach; 785 (29.3%), the extravesical approach; and 85 (3.2%), the endoscopic approach. There was no difference in terms of RFS, CSS, and OS among the three distal ureteral management approaches. Patients who underwent the endoscopic approach were at significantly higher risk of intravesical recurrence compared with those who underwent the transvesical ( p = 0.02) or extravesical approaches ( p = 0.02); the latter two groups did not differ from each other ( p = 0.40). Actuarial intravesical RFS estimates at 2 and 5 yr after RNU were 69% and 58%, 69% and 51%, and 61% and 42% for the transvesical, extravesical, and endoscopic approaches, respectively. In multivariate analyses, distal ureteral management ( p = 0.01), surgical technique (open vs laparoscopic; p = 0.02), previous bladder cancer ( p < 0.001), higher tumor stage (trend; p = 0.01), concomitant carcinoma in situ (CIS) ( p < 0.001), and lymph node involvement (trend; p < 0.001) were all associated with intravesical recurrence. Excluding patients with history of previous bladder cancer, all variables remained independent predictors of intravesical recurrence. Conclusions The endoscopic approach was associated with higher intravesical recurrence rates. Interestingly, concomitant CIS in the upper tract is a strong predictor of intravesical recurrence after RNU. The association of laparoscopic RNU with intravesical recurrence needs to be further investigated.
Abstract Background Robotic cystectomy is an emerging alternative for treatment of invasive bladder cancer (BCa). However, reduction in postoperative morbidity relative to the open approach has not ...been demonstrated. Objective To compare complication rates in patients undergoing robotic versus open radical cystectomy (RC). Design, setting, and participants A prospective cohort study of 187 consecutive patients undergoing RC at our institution—104 open RC, 83 robotic RC. Intervention Open or robotic RC with urinary diversion. Measurements Demographic, perioperative, and complication data were recorded prospectively. Thirty-day and 90-d complication rates were assessed using the modified Clavien complication scale. Data were evaluated using χ2 and multivariate logistic regression analyses. Results and limitations At 30 d, the open group demonstrated a higher overall complication rate (59% vs 41%; p = 0.04) as well as more major complications (30% vs 10%; p = 0.007). At 90 d, the overall complication rate was greater in the open group, but this was not statistically significant (62% vs 48%; p = 0.07). However, there was a significantly higher major complication rate in the open cohort (31% vs 17%; p = 0.03). When subjected to logistic regression analysis, robotic cystectomy was an independent predictor of fewer overall and major complications at 30 and 90 d. High American Society of Anesthesiologists (ASA) score (3–4) and longer surgical time were independent predictors of major complications. Though this is one of the largest published RC series, the sample size is relatively small. Moreover, despite the two patient cohorts being similarly matched, the study was not performed in a randomized fashion. Conclusions Patients undergoing robotic cystectomy experienced fewer postoperative complications than those undergoing open cystectomy. Robotic cystectomy is an independent predictor of fewer overall and major complications. Until long-term oncologic results are available, robotic cystectomy should still be considered investigational.
Abstract Background Long-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) are limited and based largely on single-institution series. Objective Report survival ...outcomes of patients who underwent RARC ≥5 yr ago. Design, setting, and participants Retrospective review of the prospectively populated International Robotic Cystectomy Consortium multi-institutional database identified 743 patients with RARC performed ≥5 yr ago. Clinical, pathologic, and survival data at the latest follow-up were collected. Patients with palliative RARC were excluded. Final analysis was performed on 702 patients from 11 institutions in 6 countries. Intervention RARC. Outcome measurements and statistical analysis Outcomes of interest, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were plotted using Kaplan-Meier survival curves. A Cox proportional hazards model was used to identify factors that predicted outcomes. Results and limitations Pathologic organ-confined (OC) disease was found in 62% of patients. Soft tissue surgical margins (SMs) were positive in 8%. Median lymph node (LN) yield was 16, and 21% of patients had positive LNs. Median follow-up was 67 mo (interquartile range: 18–84 mo). Five-year RFS, CSS, and OS were 67%, 75%, and 50%, respectively. Non-OC disease and SMs were associated with poorer RFS, CSS, and OS on multivariable analysis. Age predicted poorer CSS and OS. Adjuvant chemotherapy and positive SMs were predictors of RFS (hazard ratio: 3.20 and 2.16; p < 0.001 and p < 0.005, respectively). Stratified survival curves demonstrated poorer outcomes for positive SM, LN, and non-OC disease. Retrospective interrogation and lack of contemporaneous comparison groups that underwent open radical cystectomy were major limitations. Conclusions The largest multi-institutional series to date reported long-term survival outcomes after RARC. Patient summary Patients who underwent robot-assisted radical cystectomy for bladder cancer have acceptable long-term survival.
OBJECTIVE
To prospectively compare perioperative and pathological outcomes in a consecutive series of patients undergoing radical cystectomy (RC) and urinary diversion by the open or the robotic ...approach.
PATIENTS AND METHODS
From February 2006 to April 2007, 54 consecutive patients underwent RC by one surgeon at our institution. Twenty‐one were open, while 33 utilized the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA). Data was collected prospectively, including patient demographics, operative and postoperative variables, and pathological outcomes.
RESULTS
The robotic cohort had decreased blood loss (400 vs 750 mL, P = 0.002) and transfusion requirement (2.0 vs 0.5 units, P = 0.007), but increased operative duration (390 vs 300 min, P = 0.03). The time to resumption of a regular diet (4 vs 5 days, P = 0.002) and the hospital stay (5 vs 8 days, P = 0.007) were decreased in the robotic group. Overall the complication rates were similar (24% open, 21% robotic, P = 0.3). The open cohort had more patients with extravesical disease (57 vs 28%, P = 0.03) and nodal metastasis (34 vs 19%, P = 0.04). There were three patients in the open group and two in the robotic with positive margins (P = 0.2). The median number of lymph nodes removed was similar in the open and robotic cohorts (20 vs 17, P = 0.6).
CONCLUSION
Robotic‐assisted RC appears to offer some operative and perioperative benefits compared with the open approach without compromising pathological measures of early oncological efficacy, such as lymph node yield and margin status. Larger, randomized studies with long‐term follow‐up are required to confirm these findings and establish oncological equivalence.
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