Role of adjuvant cisplatin-based chemotherapy following radical cystectomy in locally advanced muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized trials

Purpose: We purposed to assess the effects of adjuvant chemotherapy (ACH) on survival outcomes in patients with locally advanced muscle-invasive bladder cancer (MIBC) who are treated with radical cystectomy (RC). Materials and Methods: Literature search was conducted in PubMed, Embase, and Cochrane library databases for all articles that were published until February 2018. Systematic review and meta-analysis were performed by pooling the randomized controlled trials (RCTs) that compared patients with locally advanced MIBC who received ACH after RC to those who underwent cystectomy alone. Endpoints were progression free survival (PFS) and overall survival (OS). Results: Four RCTs with a total of 490 patients were selected for the analysis. These four trials included patients with locally advanced MIBC. Pooled HRs for PFS and OS across the studies were 0.48 (95% confidence interval [CI], 0.39-0.60; p<0.00001) and 0.63 (95% CI, 0.48-0.83; p=0.0009), respectively. Absolute increases in PFS and OS for locally advanced MIBC were 17% and 10%, respectively (i.e., equivalent to numbers needed to treat of 5.9 and 10). Conclusions: ACH following RC may improve the survival outcomes of locally advanced MIBC patients. Beneficial effect of ACH might be more marked in patients with locally advanced MIBC when comparing the previously reported meta-analysis with all MIBC patients.ope

Effects of age and comorbidity on survival vary according to risk grouping among patients with prostate cancer treated using radical prostatectomy: A retrospective competing-risk analysis from the K-CaP registry.

A multicenter Korean Prostate Cancer Database (K-CaP) has been established to provide information regarding Korean patients with prostate cancer (PCa). We used the K-CaP registry to investigate the value of age and comorbidity for predicting cancer-specific mortality (CSM) and other-cause mortality (OCM) according to risk grouping.The K-CaP registry includes 2253 patients who underwent radical prostatectomy (RP) between May 2001 and April 2013 at 5 institutions. Preoperative clinicopathologic data were collected and stratified according to the National Comprehensive Cancer Network risk criteria. Survival was evaluated using Gray's modified log-rank test according to risk category, age (<70 years vs ≥70 years), and Charlson comorbidity index (CCI) (0 vs ≥1).The median follow-up was 55.0 months (interquartile range: 42.0-70.0 months). Competing-risk regression analysis revealed that, independent of CCI, ≥70-year-old high-risk patients had significantly greater CSM than <70-year-old high-risk patients (P = .019). However, <70-year-old high-risk patients with a CCI of ≥1 had similar CSM relative to ≥70-year-old patients. Survival was not affected by age or CCI among low-risk or intermediate-risk patients. Multivariate analysis revealed that a CCI of ≥1 was independently associated with a higher risk of CSM (P = .003), while an age of ≥70 years was independently associated with a higher risk of OCM (P = .005).Age and comorbidity were associated with survival after RP among patients with high-risk PCa, although these associations were not observed among low-risk or intermediate-risk patients. Therefore, older patients with high-risk diseases and greater comorbidity may require alternative multidisciplinary treatment.ope

Effect of Androgen-Deprivation Therapy on Bone Mineral Density in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis

We aimed to evaluate the change in bone mineral density (BMD) in patients with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) compared to those with PCa or other urologic conditions not receiving ADT. Literature searches were conducted throughout October 2018. The eligibility of each study was assessed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the Participant, Intervention, Comparator, Outcome, and Study design method. The outcomes analyzed were the mean difference (MD) of percent changes in BMD of lumbar spine, femur neck, and total hip. Five prospective cohort studies with a total of 533 patients were included in the present study. Statistically significant decreases of BMD change relative to the control group were observed in the ADT treatment group in the lumbar spine (MD -3.60, 95% CI -6.72 to -0.47, P = 0.02), femoral neck (MD -3.11, 95% CI -4.73 to -1.48, P = 0.0002), and total hip (MD -1.59, 95% CI -2.99 to -0.19, P = 0.03). There is a significant relationship between ADT and BMD reduction in patients with PCa. Regular BMD testing and the optimal treatment for BMD loss should, therefore, be considered in patients with PCa undergoing ADT.ope

What is the most effective local anesthesia for transrectal ultrasonography-guided biopsy of the prostate? A systematic review and network meta-analysis of 47 randomized clinical trials

We aimed to compare the effectiveness of various local anesthetic methods for controlling prostate biopsy (PBx) related pain using network meta-analysis. Literature searches were performed on PubMed/Medline, Embase, and Cochrane Library up to March 2018. Forty-seven randomized controlled trials, in which the effectiveness of PBx-related pain was investigated using a visual analogue scale after various local anesthetic methods, were included. The local anesthetic methods included intraprostatic local anesthesia (IPLA), intrarectal local anesthesia (IRLA), intravenous sedation (IVS), periprostatic nerve block (PNB), pelvic plexus block (PPB), and spinal anesthesia (SPA). Eight pairwise meta-analyses and network meta-analyses with 21 comparisons were performed. All modalities, except single use of IPLA and IRLA, were more effective than placebo. Our results demonstrate that PNB + IVS (rank 1) and SPA (rank 2) were the most effective methods for pain control. The followings are in order of PPB + IRLA, PNB + IPLA, PPB, PNB + IRLA, IVS, and PNB. In conclusion, the most effective way to alleviate PBx-related pain appears to be PNB + IVS and SPA. However, a potential increase in medical cost and additional risk of morbidities should be considered. In the current outpatient setting, PPB + IRLA, PNB + IPLA, PPB, PNB + IRLA, and PNB methods are potentially more acceptable options.ope

Time to Disease Recurrence Is a Predictor of Metastasis and Mortality in Patients with High-risk Prostate Cancer Who Achieved Undetectable Prostate-specific Antigen Following Robot-assisted Radical Prostatectomy

Background: Robot-assisted radical prostatectomy (RARP) is a feasible treatment option for high-risk prostate cancer (PCa). While patients may achieve undetectable prostate-specific antigen (PSA) levels after RARP, the risk of disease progression is relatively high. We investigated metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS) outcomes and prognosticators in such patients. Methods: In a single-center cohort of 342 patients with high-risk PCa (clinical stage ≥ T3, biopsy Gleason score ≥ 8, and/or PSA levels ≥ 20 ng/mL) treated with RARP and pelvic lymph node dissection between August 2005 and June 2011, we identified 251 (73.4%) patients (median age, 66.5 years; interquartile range [IQR], 63.0-71.0 years) who achieved undetectable PSA levels (< 0.01 ng/mL) postoperatively. Survival outcomes were evaluated for the entire study sample and in groups stratified according to the time to biochemical recurrence dichotomized at 60 months. Results: During the median follow-up of 75.9 months (IQR, 59.4-85.8 months), metastasis occurred in 38 (15.1%) patients, most often to the bones, followed by the lymph nodes, lungs, and liver. The 5-year metastasis-free, cancer-specific, and OS rates were 87.1%, 94.8%, and 94.3%, respectively. Multivariate Cox-regression analysis revealed time to recurrence as an independent predictor of metastasis (P < 0.001). Time to metastasis was an independent predictor of OS (P = 0.003). Metastasis-free and CSS rates were significantly lower among patients with recurrence within 60 months of RARP (log-rank P < 0.001). Conclusion: RARP confers acceptable oncological outcomes for high-risk PCa. Close monitoring beyond 5 years is warranted for early detection of disease progression and for timely adjuvant therapy.ope

Impact of clinical trial participation on survival in patients with castration-resistant prostate cancer: a multi-center analysis

BACKGROUND: Clinical trial (CT) participation may confer access to new, potentially active agents before their general availability. This study aimed to investigate the potential survival benefit of participation in investigational CTs of novel hormonal, chemotherapeutic, and radiopharmaceutical agents in patients with castration-resistant prostate cancer (CRPC). METHODS: This multi-center, retrospective analysis included 299 consecutive patients with newly diagnosed, non-metastatic or metastatic CRPC between September 2009 and March 2017. Of these, 65 (21.7%) patients participated in CTs pertaining to systemic treatment targeting CRPC and 234 (78.3%) patients received pre-established, standard systemic treatment outside of a CT setting. The survival advantage of CT participation regarding cancer-specific survival (CSS) was investigated. RESULTS: An Eastern Cooperative Oncology Group performance status (ECOG PS) >/=2 at CRPC diagnosis was found in a lower proportion CT participants than in non-participants (4.6% vs. 14.9%; p = 0.033). During the median follow-up period of 16.0 months, CT participants exhibited significantly higher 2-year CSS survival rates (61.3% vs. 42.4%; p = 0.003) than did non-participants. Multivariate analysis identified prostate-specific antigen and alkaline phosphatase levels at CRPC onset, Gleason score >/= 8, ECOG PS >/=2, less number of docetaxel cycles administered, and non-participation in CTs as independent predictors for a lower risk of CSS. CONCLUSIONS: Patients diagnosed with CRPC who participated in CTs exhibited longer CSS durations than non-participants who received pre-established, standard systemic therapy outside of a CT setting. Our findings imply that CT participation is associated with CSS, and that CT participation should be offered to patients with CRPC whenever indicated.ope