To improve the prognosis of upper tract urothelial carcinoma (UTUC), clinicians have used neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) before or after radical nephroureterectomy ...(RNU). Despite some new data, the evidence remains mixed on their efficacy.
To update the current evidence on the role of NAC and AC for UTUC.
We searched for all studies investigating NAC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings up to February 2020. A systematic review and meta-analysis was performed.
For NAC, the pooled pathologic complete response rate (≤ypT0N0M0) was 11% (n = 811) and pathologic partial response rate (≤ypT1N0M0) was 43% (n = 869), both across 14 studies. Across six studies, the pooled hazard ratios (HRs) were 0.44 (95% confidence interval CI: 0.32–0.59, p < 0.001) for overall survival (OS) and 0.38 (95% CI: 0.24–0.61, p < 0.001) for cancer-specific survival (CSS) in favor of NAC. The evidence for NAC is at best level 2. As for AC, there was a benefit in OS (pooled HR 0.77; 95% CI: 0.64–0.92, p = 0.004 across 14 studies and 7983 patients), CSS (pooled HR 0.79; 95% CI: 0.69–0.91, p = 0.001 across 18 studies and 5659 patients), and disease-free survival (DFS; pooled HR 0.52; 95% CI: 0.38–0.70 across four studies and 602 patients). While most studies were retrospective (level 2 evidence), there were two prospective randomized trials providing level 1 evidence. There are currently four phase 2 trials on neoadjuvant immunotherapy and three phase 2 trials on adjuvant immunotherapy for UTUC.
NAC for UTUC confers a favorable pathologic response and tumor downstaging rate, and an OS and CSS benefit compared with RNU alone. AC confers an OS, CSS, and DFS benefit compared with RNU alone. Currently, the evidence for AC appears stronger (with positive level 1 evidence) than that for NAC (at best level 2 evidence). Limited data are available for chemoimmunotherapy approaches, but preliminary data support an active research investment.
After a comprehensive search of the latest studies examining the role of neoadjuvant and adjuvant chemotherapy for upper tract urothelial cancer, the pooled evidence shows that perioperative chemotherapy was beneficial for prolonging survival; however, the evidence for adjuvant chemotherapy was stronger than that for neoadjuvant chemotherapy.
Both neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma found to confer survival benefit over radical nephroureterectomy alone. Evidence for adjuvant chemotherapy appears stronger, while that for immunotherapy is promising.
High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non-muscle-invasive bladder cancer, with highly variable prognosis, poorly understood risk factors, and considerable debate about ...the role of early cystectomy. We aimed to address these questions through a meta-analysis of outcomes and prognostic factors.
PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and American Society of Clinical Oncology abstracts were searched for cohort studies in HGT1. We pooled data on recurrence, progression, and cancer-specific survival from 73 studies.
Five-year rates of recurrence, progression, and cancer-specific survival were 42% (95% CI, 39% to 45%), 21% (95% CI, 18% to 23%), and 87% (95% CI, 85% to 89%), respectively (56 studies, n = 15,215). In the prognostic factor meta-analysis (33 studies, n = 8,880), the highest impact risk factor was depth of invasion (T1b/c) into lamina propria (progression: hazard ratio HR, 3.34; P < .001; cancer-specific survival: HR, 2.02; P = .001). Several other previously proposed factors also predicted progression and cancer-specific survival (lymphovascular invasion, associated carcinoma in situ, nonuse of bacillus Calmette-Guérin, tumor size > 3 cm, and older age; HRs for progression between 1.32 and 2.88, P ≤ .002; HRs for cancer-specific survival between 1.28 and 2.08, P ≤ .02).
In this large analysis of outcomes and prognostic factors in HGT1 bladder cancer, deep lamina propria invasion had the largest negative impact, and other previously proposed prognostic factors were also confirmed. These factors should be used for prognostication and patient stratification in future clinical trials, and depth of invasion should be considered for inclusion in TNM staging criteria. This meta-analysis can also help define selection criteria for early cystectomy in HGT1 bladder cancer, particularly for patients with deep lamina propria invasion combined with other risk factors.
Purpose We evaluate the current literature comparing outcomes of robotic vs laparoscopic partial nephrectomy. Materials and Methods We performed a literature search according to Cochrane guidelines ...up to December 2015 including studies comparing robotic and laparoscopic partial nephrectomy, and we compared baseline patient and tumor characteristics. We performed a meta-analysis to evaluate safety, effectiveness and functional outcomes of robotic vs laparoscopic partial nephrectomy using weighted mean difference and inverse variance pooled risk ratios, respectively. Results A total of 4,919 patients were included from 25 studies (robotic partial nephrectomy 2,681; laparoscopic partial nephrectomy 2,238). There were no significant differences between the 2 groups in terms of age, gender, laterality and final malignant pathology. Patients treated with robotic partial nephrectomy had larger tumors (WMD 0.17 cm, p=0.001) and higher mean R.E.N.A.L. nephrometry scores (WMD 0.59, p=0.002), and were associated with a decreased likelihood of conversion to laparoscopic/open surgery compared to laparoscopic partial nephrectomy (RR 0.36, p <0.001), any (Clavien 1 or greater) (RR 0.84, p=0.007) and major (Clavien 3 or greater) (RR 0.71, p=0.023) complications, positive margins (RR 0.53, p <0.001) and shorter warm ischemia time by 4.3 minutes (p <0.001). Both approaches had similar operative times (WMD −12.2 minutes, p=0.34), estimated blood loss (WMD −24.6 ml, p=0.15) and postoperative change in estimated glomerular filtration rate. Conclusions This updated meta-analysis of retrospective cohort studies demonstrated that robotic partial nephrectomy confers a superior morbidity profile compared to laparoscopic partial nephrectomy in most of the examined perioperative outcomes. Despite being the strongest available evidence (Level 2b) for outcomes of robotic vs laparoscopic partial nephrectomy thus far, there have been no completed or ongoing randomized trials to lend Level 1 support for either approach.
Abstract Context The role of adjuvant chemotherapy remains poorly defined for the management of muscle-invasive bladder cancer (MIBC). The last meta-analysis evaluating adjuvant chemotherapy, ...conducted in 2005, had limited power to fully support its use. Objective To update the current evidence of the benefit of postoperative adjuvant cisplatin-based chemotherapy compared with control (ie, surgery alone) in patients with MIBC. Evidence acquisition A comprehensive literature review was performed to identify all randomized controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy with control for patients with MIBC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to May 2013. An updated systematic review and meta-analysis was performed. Evidence synthesis A total of 945 patients included in nine RCTs (five previously analyzed, one updated, and three new) were examined. For overall survival, the pooled hazard ratio (HR) across all nine trials was 0.77 (95% confidence interval CI, 0.59–0.99; p = 0.049). For disease-free survival, the pooled HR across seven trials reporting this outcome was 0.66 (95% CI, 0.45–0.91; p = 0.014). This disease-free survival benefit was more apparent among those with positive nodal involvement ( p = 0.010). Conclusions This updated and improved meta-analysis of randomized trials provides further evidence of an overall survival and disease-free survival benefit in patients with MIBC receiving adjuvant cisplatin-based chemotherapy after radical cystectomy.
Abstract Context The role of adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NC) remains poorly defined for the management of upper tract urothelial carcinoma (UTUC), although some studies ...suggest a benefit. Objective To update the current evidence on the role of NC and AC for UTUC patients. Evidence acquisition We searched for all studies investigating NC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings prior to February 2014. A systematic review and meta-analysis were performed. Evidence synthesis No randomized trials investigated the role of AC for UTUC. There was one prospective study ( n = 36) investigating adjuvant carboplatin–paclitaxel and nine retrospective studies, with a total of 482 patients receiving cisplatin-based or non-cisplatin–based AC after nephroureterectomy (NU) and 1300 patients receiving NU alone. Across three cisplatin-based studies, the pooled hazard ratio (HR) for overall survival (OS) was 0.43 (95% confidence interval CI, 0.21–0.89; p = 0.023) compared with those who received surgery alone. For disease-free survival (DFS), the pooled HR across two studies was 0.49 (95% CI, 0.24–0.99; p = 0.048). Benefit was not seen for non-cisplatin–based regimens. For NC, two phase 2 trials demonstrated favorable pathologic downstaging rates, with 3-yr OS and disease-specific survival (DSS) ≤93%. Across two retrospective studies investigating NC, there was a DSS benefit, with a pooled HR of 0.41 (95% CI, 0.22–0.76; p = 0.005). Conclusions There appears to be an OS and DFS benefit for cisplatin-based AC in UTUC. This evidence is limited by the retrospective nature of studies and their relatively small sample size. NC appears to be promising, but more trials are needed to confirm its utility. Patient summary After a comprehensive search of studies examining the role of chemotherapy for upper tract urothelial cancer, the pooled evidence shows that cisplatin-based adjuvant chemotherapy was beneficial for prolonging survival.
Abstract Background More than a decade since its inception, the benefits and cost efficiency of robot-assisted radical prostatectomy (RARP) continue to elicit controversy. Objective To compare ...outcomes and costs between RARP and open RP (ORP). Design, setting, and participants A cohort study of 629 593 men who underwent RP for localized prostate cancer at 449 hospitals in the USA from 2003 to 2013, using the Premier Hospital Database. Intervention RARP was ascertained through a review of the hospital charge description master for robotic supplies. Outcome measures and statistical analysis Outcomes were 90-d postoperative complications (Clavien), blood product transfusions, operating room time (ORT), length of stay (LOS), and direct hospital costs. Propensity-weighted regression analyses accounting for clustering by hospitals and survey weighting ensured nationally representative estimates. Results and limitations RARP utilization rapidly increased from 1.8% in 2003 to 85% in 2013 ( p < 0.001). RARP patients ( n = 311 135) were less likely to experience any complications (odds ratio OR 0.68, p < 0.001) or prolonged LOS (OR 0.28, p < 0.001), or to receive blood products (OR 0.33, p = 0.002) compared to ORP patients ( n = 318 458). The adjusted mean ORT was 131 min longer for RARP ( p = 0.002). The 90-d direct hospital costs were higher for RARP (+$4528, p < 0.001), primarily attributed to operating room and supplies costs. Costs were no longer signficantly different between ORP and RARP among the highest-volume surgeons (≥104 cases/yr; +$1990, p = 0.40) and highest-volume hospitals (≥318 cases/yr; +$1225, p = 0.39). Limitations include the lack of oncologic characteristics and the retrospective nature of the study. Conclusions Our contemporary analysis reveals that RARP confers a perioperative morbidity advantage at higher cost. In the absence of large randomized trials because of the widespread adoption of RARP, this retrospective study represents the best available evidence for the morbidity and cost profile of RARP versus ORP. Patient summary In this large study of men with prostate cancer who underwent either open or robotic radical prostatectomy, we found that robotic surgery has a better morbidity profile but costs more.
Abstract Background Radical cystectomy (RC) is a morbid procedure associated with high costs. Limited population-based data exist on the complication profile and costs of robot-assisted RC (RARC) ...compared with open RC (ORC). Objective To evaluate morbidity and cost differences between ORC and RARC. Design, setting, and participants We conducted a population-based, retrospective cohort study of patients who underwent RC at 279 hospitals across the United States between 2004 and 2010. Outcome measurements and statistical analysis Multivariable logistic and median regression was performed to evaluate 90-d mortality, postoperative complications (Clavien classification), readmission rates, length of stay (LOS), and direct costs. To reduce selection bias, we used propensity weighting with survey weighting to obtain nationally representative estimates. Results and limitations The final weighted cohort included 34 672 ORC and 2101 RARC patients. RARC use increased from 0.6% in 2004 to 12.8% in 2010. Major complication rates (Clavien grade ≥3; 17.0% vs 19.8%, p = 0.2) were similar between ORC and RARC (odds ratio OR: 1.32; p = 0.42). RARC had 46% decreased odds of minor complications (Clavien grade 1–2; OR: 0.54; p = 0.03). RARC had $4326 higher adjusted 90-d median direct costs ( p = 0.004). Although RARC had a significantly shorter LOS (11.8 d vs 10.2 d; p = 0.008), no significant differences in room and board costs existed ( p = 0.20). Supply costs for RARC were significantly higher ($6041 vs $3638; p < 0.0001). Morbidity and cost differences were not present among the highest-volume surgeons (≥7 cases per year) and hospitals (≥19 cases per year). Limitations include use of an administrative database and lack of oncologic characteristics. Conclusions The use of RARC has increased between 2004 and 2010. Compared with ORC, RARC was associated with decreased odds of minor but not major complications and with increased expenditures attributed primarily to higher supply costs. Centralization of ORC and RARC to high-volume providers may minimize these morbidity and cost differences. Patient summary Using a US population–based cohort, we found that robotic surgery for bladder cancer decreased minor complications, had no impact on major complications and was more costly than open surgery.
Abstract Given the lack of randomized evidence comparing trimodal therapy (TMT) to radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB), we performed an observational ...cohort study to examine the comparative effectiveness of these two definitive treatments. Within the National Cancer Data Base (2004–2011),we identified 1257 (9.8%) and 11 586 (90.2%) patients who received TMT and RC, respectively. Inverse probability of treatment weighting (IPTW)–adjusted Kaplan-Meier analysis showed that median overall survival (OS) was similar between the TMT (40 mo, 95% confidence interval CI 34–46) and RC groups (43 mo 95% CI 41–45; p = 0.3). In IPTW-adjusted Cox regression analysis with a time-varying covariate, TMT was associated with a significant adverse impact on long-term OS (hazard ratio 1.37, 95% CI 1.16–1.59; p < 0.001). Interaction terms indicated that the adverse treatment effect of TMT versus RC decreased with age ( p = 0.004), while there was no significant interaction with gender ( p = 0.6), Charlson comorbidity index ( p = 0.09) or cT stage ( p = 0.8). In conclusion, we found that TMT was generally associated with worse long-term OS compared to RC for muscle-invasive UCB. However, the survival benefit of RC should be weighed against the risks of surgery, especially in older patients. These results are preliminary and emphasize the need for a randomized controlled trial to compare TMT versus RC. Patient summary We examined the comparative effectiveness of trimodal therapy versus radical cystectomy for muscle-invasive urothelial carcinoma of the bladder. We found that trimodal therapy was generally associated with worse long-term overall survival, although there may be no difference with radical cystectomy in older individuals.
Purpose There is limited evidence to support the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we ...hypothesized that such treatment is associated with overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Patients and Methods Within the National Cancer Database (2004 to 2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW) -adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare OS of patients in the two treatment groups. In addition, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathologic stage (pT3/T4N0, pT3/T4Nx and pTanyN+), and surgical margin status. Results Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation, respectively, after RNU. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation (47.41 interquartile range,19.88 to 112.39 v 35.78 interquartile range, 14.09 to 99.22 months; P < .001). The 5-year IPTW-adjusted rates of OS for AC versus observation were 43.90% and 35.85%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit (hazard ratio, 0.77 95% CI, 0.68 to 0.88; P < .001). This benefit was consistent across all subgroups examined (all P < .05), and no significant heterogeneity of treatment effect was observed (all P
> .05). Conclusion We report an OS benefit in patients who received AC versus observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.
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