Purpose We evaluated the association of soft tissue surgical margins with characteristics and outcomes of patients treated with radical cystectomy for urothelial carcinoma of the bladder. Materials ...and Methods We retrospectively collected the data of 4,410 patients treated with radical cystectomy and pelvic lymphadenectomy without neoadjuvant chemotherapy at 12 academic centers in the United States, Canada and Europe. A positive soft tissue surgical margin was defined as presence of tumor at inked areas of soft tissue on the radical cystectomy specimen. Results Positive soft tissue surgical margins were identified in 278 patients (6.3%). On univariate analysis positive soft tissue surgical margin was significantly associated with advanced pT stage, higher tumor grade, lymphovascular invasion and lymph node metastasis (p <0.001). Actuarial 5-year recurrence-free and cancer specific survival probabilities were 62.8% ± 0.8% and 69% ± 0.8% for patients without soft tissue surgical margins vs 21.6% ± 3.1% and 26.4% ± 3.3% for those with positive soft tissue surgical margins (p <0.001). On multivariable analyses adjusting for the effect of standard clinicopathological features and adjuvant chemotherapy positive soft tissue surgical margin was an independent predictor of disease recurrence and cancer specific mortality (HR 1.52 and HR 1.51, p <0.001, respectively). Soft tissue surgical margin retained independent predictive value in subgroups with advanced disease such as pT3Nany, pT4Nany or Npositive. Conclusions Positive soft tissue surgical margin is a strong predictor of recurrence and eventual death from urothelial carcinoma of the bladder. Soft tissue surgical margin status should always be reported in the pathological reports after radical cystectomy. Due to uniformly poor outcomes patients with positive soft tissue surgical margins should be considered for studies on adjuvant local and/or systemic therapy.
Purpose
Ileal conduit (IC) is the most frequent urinary diversion (UD) performed after radical cystectomy (RC). We reviewed the literature to investigate the factors influencing the choice of this ...diversion and its complications.
Methods
A literature search (PubMed) was performed for all English language publications on UDs performed for treatment of bladder cancer from 1950 to 2015. The literature review was focused on studies reporting outcome of IC and its comparison with other types of UDs.
Results
IC is the most common UD performed in elderly patients undergoing RC for bladder cancer. Long-term studies looking at the change in renal function after UD report a universal decline in the glomerular filtration rate; however, this decline in renal function is the least for IC. There is a significant morbidity of RC (20–56 %), which can be attributed to patient factors, surgical technique and hospital volume. Modern concepts of bowel preparation, postoperative nutrition, early enteral feeding and involvement of stoma therapists have helped improve the outcomes. The quality of life is preserved, and in many including elderly, it may be improved with IC UD.
Conclusions
IC is the most commonly performed UD following radical cystectomy. It is associated with acceptable morbidity and has the lowest reoperation rates as compared to continent diversion. It is also the procedure of choice for most patients’ elderly patients as well as patients with limited dexterity, poor motivation, anatomical restrictions and poor renal function. Studies measuring HRQOL report excellent patient acceptability, especially in the elderly population.
Study Type – Prognosis (case series) Level of Evidence 4
What’s known on the subject? and What does the study add?
Observations from small retrospective studies have indicated that a considerable ...number of patients undergoing radical cystectomy for bladder cancer experience a stage migration (either upstaging or downstaging) when comparing clinical and pathological staging. In addition, it is unclear if pathological upstaging is an adverse prognostic feature independent of pathological stage.
We report the frequency of upstaging and downstaging using a large, international multicentre cohort of patients undergoing radical cystectomy for bladder cancer without neoadjuvant chemotherapy. Our findings indicate that pathological upstaging is not an independent adverse prognostic feature when considering pathological stage.
OBJECTIVE
• To compare the clinical and pathologic stage among a large, multi‐institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes.
PATIENTS AND METHODS
• Data was collected from nine centers and 3,393 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and pelvic lymphadenectomy without neo‐adjuvant chemotherapy.
• A retrospective cohort design was used to assess the percentage of patients experiencing stage discrepancy and the impact of stage discrepancy on time to disease relapse and time to death from UCB.
RESULTS
• Clinical under staging occurred in 50% of patients and pathologic down staging occurred in 18% of patients.
• Up staging to muscle invasive disease occurred in 45.9% (n = 592) of 1,291 patients with clinical ≤T1, including 30.6% of patients with Tis only at transurethral resection.
• Of the 3,166 patients with clinically organ confined (OC) tumor stage, 1,357 (42.9%) were up staged to non‐organ confined pathologic tumor stage.
• Within each clinical stage stratum, patients who were clinically under staged had a higher probability of disease relapse or death from UCB compared to those who were same staged or down staged on pathologic examination (P < 0.05).
CONCLUSIONS
• We identified clinical under staging in half of the patients undergoing radical cystectomy for UCB.
• Up staging resulted in a higher likelihood of disease progression and eventual death from UCB.
• These findings should be considered when utilizing pre‐operative risk‐adapted strategies for selecting candidates for neoadjuvant chemotherapy.
To compare radical prostatectomy outcomes in men with and without exposure to a major infectious event within 30-days of a prior TRUS-biopsy.
This retrospective cohort study included men who ...underwent radical prostatectomy from 2002 to 2013 in Ontario, Canada. Several linked administrative databases were used. Exposure was defined as hospitalization with evidence of a urinary tract infection or sepsis during the first 30-days after a prostate biopsy. The primary outcome was a composite of procedures indicative of a likely serious complication of radical prostectomy within the first 12 months after surgery. Secondary outcomes included oncological, functional, and hospital related events within 2 years of radical prostatectomy.
A total of 26,254 patients were included in this study and 530 (2.02%) had a post-TRUS-biopsy infection. A similar proportion of patients with and without a post-TRUS-biopsy infectious event experienced the composite primary outcome (1.7% vs 1.1%; odds ratio OR 1.61, 95% confidence interval CI 0.82-3.14; P = .16). However, exposed patients had significantly higher odds of perioperative blood transfusion (OR 1.61, 95% CI 1.30-2.00; P <.001), bladder neck contracture (OR 1.35, 95% CI 1.12-1.63; P = .002), and 30-day hospital readmission (OR 2.08, 95% CI 1.47-2.95; P <.001), and a small but significant increase in length of hospital stay (P = 0.005). No other significant differences were observed.
Although prior infectious events are associated with increased risk of blood transfusion, bladder neck contracture, and hospital readmission following radical prostatectomy, results from this study suggest that major surgical complications, are not adversely affected by TRUS-biopsy related infections.
Abstract Objective To evaluate the impact of multiple transrectal ultrasound-guided prostate biopsies (TRUS-Bx) before radical prostatectomy (RP) on surgical outcomes. Methods Administrative ...databases were used to identify all patients who had a RP performed in the province of Ontario from April 1, 2002 to March 31, 2013. TRUS-Bx prior to RP were identified and patients were categorized as having one or more than one prior TRUS-Bx. The primary end point was a composite index of serious surgical complications. Secondary outcomes included oncological interventions, functional-related events, and general health service-related outcomes. Results Among 27,637 patients, 4780 (17.3%) had ≥2 biopsies performed before RP. The proportion of patients who experienced the composite end point was similar between those with one TRUS-Bx compared to those with ≥2 TRUS-Bx (1.05% vs 1.19%, OR 1.14, 95% CI 0.85-1.52). Patients with ≥ 2 biopsies were more likely to have a perioperative blood transfusion compared to patients with only one biopsy (15.5% vs 12.8%, OR 1.25, 95% CI 1.15-1.37), while readmission rate and 30-day mortality were similar. The need for radiotherapy and androgen deprivation therapy within the first year after RP was higher in patients with a single biopsy. Patients with multiple TRUS-Bx were more likely to require post-RP urodynamic evaluation and bladder neck contracture-related interventions but were not at increased odds of surgery for incontinence or erectile dysfunction. Conclusions Perioperative outcomes after RP are similar between men with single or multiple TRUS-Bx, although multiple TRUS-Bx was associated with an increased odds of perioperative blood transfusion.
Objective To determine the association of gender with outcome after radical cystectomy for patients with bladder cancer. Methods An observational cohort study was conducted using retrospectively ...collected data from 11 centers on patients with advanced bladder cancer treated with radical cystectomy. The association of gender with disease recurrence and cancer-specific mortality was examined using a competing risk analysis. Results The study comprised 4296 patients, including 890 women (21%). The median follow-up duration was 31.5 months for all patients. Disease recurred in 1430 patients (33.9%) (36.8% of women and 33.1% of men) at a median of 11 months after surgery. Death from any cause was observed in 46.0% of men and 50.1% of women. Cancer-specific death was observed in 33.0% of women and 27.2% of men. Multivariable regression with competing risk found that female gender was associated with an increased risk for disease recurrence and cancer-specific mortality (hazard ratio, 1.27; 95% confidence interval, 1.108-1.465; P = .007) compared with male gender. Important limitations include the inability to account for additional potential confounders, such as differences in environmental exposures, treatment selection, and histologic subtypes between men and women. Conclusion Our analysis identified female gender as a poor-risk feature for patients undergoing radical cystectomy. This adverse prognostic factor was independent of standard clinical and pathologic features and competing risk from non–cancer-related death.
Objective
To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to ...identify patient subgroups that are most likely to benefit from AC.
Patients and methods
We retrospectively analysed data of 263 patients with LN‐positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC‐related mortality was evaluated using competing‐risks regression models.
Results
In all patients (Tall N+), administration of AC had no significant impact on UTUC‐related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3–4 disease benefited from AC. In this subgroup, AC reduced UTUC‐related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC‐related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non‐randomised design, selection bias, absence of a central pathological review and different AC protocols.
Conclusions
AC seems to reduce mortality in patients with pT3–4 LN‐positive UTUC after RNU. This subgroup of LN‐positive patients could serve as target population for an AC prospective randomised trial.
Bladder cancer can be classified histologically as urothelial or non-urothelial. Urothelial cancer has a propensity for divergent differentiation, which has increasingly been recognized in recent ...years due to heightened awareness and improved immunohistochemistry techniques. Furthermore, the recent World Health Organization classification of urothelial cancers improved clarity on this issue, with its listing of 13 histologic variants of urothelial cancer. The divergent differentiation patterns include, amongst others, squamous, glandular, micropapillary, nested, lymphepithelioma-like, plasmacytoid and sarcomatoid variants of urothelial cancer. Attempts to quantify the amount of divergent differentiation present, such as using the nonconventional differentiation number, have been made recently, which will improve the ability to compare publications from different centres. Genetic-based studies have indicated that the histologic variants of urothelial cancer arise from a common clonal precursor. Mostly, the current evidence suggests that urothelial cancer with divergent differentiation has a worse prognosis when compared with pure urothelial cancer. This article will review the current literature on variant histologies of urothelial cancer, and well as new developments in pure squamous cell carcinoma, small cell carcinoma and adenocarcinoma of the bladder.
The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing ...radical cystectomy for UCB in an off-protocol routine clinical setting.
We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles.
The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (> or =T(3)) and nodal involvement.
Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.
A novel TRIM family member, TRIM59 gene was characterized to be upregulated in SV40 Tag oncogene-directed transgenic and knockout mouse prostate cancer models as a signaling pathway effector. We ...identified two phosphorylated forms of TRIM59 (p53 and p55) and characterized them using purified TRIM59 proteins from mouse prostate cancer models at different stages with wild-type mice and NIH3T3 cells as controls. p53/p55-TRIM59 proteins possibly represent Ser/Thr and Tyr phosphorylation modifications, respectively. Quantitative measurements by ELISA showed that the p-Ser/Thr TRIM59 correlated with tumorigenesis, whereas the p-Tyr-TRIM59 protein correlated with advanced cancer of the prostate (CaP). The function of TRIM59 was elucidated using short hairpin RNA (shRNA)-mediated knockdown of the gene in human CaP cells, which caused S-phase cell-cycle arrest and cell growth retardation. A hit-and-run effect of TRIM59 shRNA knockdown was observed 24 hours posttransfection. Differential cDNA microarrray analysis was conducted, which showed that the initial and rapid knockdown occurred early in the Ras signaling pathway. To confirm the proto-oncogenic function of TRIM59 in the Ras signaling pathway, we generated a transgenic mouse model using a prostate tissue-specific gene (PSP94) to direct the upregulation of the TRIM59 gene. Restricted TRIM59 gene upregulation in the prostate revealed the full potential for inducing tumorigenesis, similar to the expression of SV40 Tag, and coincided with the upregulation of genes specific to the Ras signaling pathway and bridging genes for SV40 Tag-mediated oncogenesis. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy for cancer.
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