Pathological response and survival outcomes after neoadjuvant chemotherapy with radical cystectomy in octogenarians for muscle-invasive bladder cancer: an observational database study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) with radical cystectomy (RC) is the preferred first-line treatment for localized muscle-invasive bladder cancer (MIBC). In recent years, octogenarians have been undergoing RC uneventfully, but studies showed older adults receive NAC less often. We studied the utilization and effect of RC with or without NAC in octogenarians and compared survival outcomes between responders and non-responders. METHODS: In our retrospective study using the National Cancer Database (NCDB), we identified octogenarians with MIBC and urothelial histology who underwent RC with or without NAC between 2004 and 2018. The NAC cohort included patients who underwent RC with NAC, and the non-NAC cohort included those with or without adjuvant chemotherapy. The NAC cohort was subcategorized into responders and non-responders based on surgical pathology. Patients with comorbidity index > 1 were not included, thereby excluding patients with possible renal impairment. After propensity-matching, we compared the overall survival (OS) between NAC and non-NAC cohorts and responders and non-responders. RESULTS: 33924 patients underwent RC, and 3056 octogenarians met our selection. Among them, 396 received NAC, and 2660 did not receive NAC. Among those who received NAC, 112(28.3%) experienced downstaging, and 223(56.4%) exhibited upstaging or no change (p < 0.001). After propensity-matching, the median OS of the NAC and non-NAC cohorts were 51.6 months and 31.3 months, respectively (p<0.001). Similarly, the median OS of responders and non-responders were 89.4 months and 26.5 months, respectively(p < 0.0001). CONCLUSION: In our study, we observed that NAC with RC for MIBC may help to improve OS among healthy octogenarians. Similarly, responders had better OS than non-responders.

Racial and ethnic disparities in prostate cancer screening following the 2018 US Preventive Services Task Force recommendation statement.

OBJECTIVE: In 2018, the United States Preventive Services Task Force promoted shared decision making between healthcare provider and patient for men aged 55 to 69. This study aimed to analyze rates of prostate-specific antigen (PSA) testing across racial and ethnic groups following this new recommendation. METHODS: A secondary analysis was conducted of the 2020-2021 Behavioral Risk Factor Surveillance System database to assess men aged 55 or older without a history of prostate cancer. We defined four race-ethnicity groups: non-Hispanic Whites (NHWs), non-Hispanic Blacks (NHBs), Hispanics, and Other. The primary outcome was the most recent PSA test (MRT), defined as the respondent's most recent PSA test occurring pre-2018 or post-2018 guidelines. Logistic regression adjusted for covariates including age, socioeconomic status factors, marital status, smoking history, and healthcare access factors. RESULTS: In the age 55 to 69 study sample, NHW men had the greatest proportion of MRT post-2018 guidelines (n = 15,864, 72.5%). NHB men had the lowest percentage of MRT post-2018 guidelines (n = 965, 66.6%). With NHW as referent, the crude odds of the MRT post-2018 guidelines was 0.68 (95% confidence interval (CI) = 0.53-0.90) for NHB. The maximally adjusted odds ratio was 0.78 (0.59-1.02). CONCLUSIONS: We found that NHB aged 55 to 69 reported decreased rates of PSA testing after 2018 when compared to NHW. This was demonstrated on crude analysis but not after adjustment. Such findings suggest the influence of social determinants of health on preventative screening for at-risk populations.

Irreversible electroporation as a focal therapy for localized prostate cancer: A systematic review.

Introduction: Irreversible electroporation (IRE) is a new and promising focal therapy for the treatment of localized prostate cancer. In this systematic review, we summarize the literature on IRE for prostate cancer published over the last decade. Methods: PubMed and EMBASE were searched with the end date of May 2023 to find relevant publications on prostate cancer ablation using IRE. Original studies with focal IRE as the primary curative treatment which reported on functional or oncological outcomes were included. The bibliography of relevant studies was also scanned to identify suitable articles. Results: A total of 14 studies reporting on 899 patients treated with IRE for localized prostate cancer were included. Of all the studies reviewed, 77% reported on recurrence within the zone of ablation, and it ranged from 0% to 38.9% for in-field and 3.6% to 28% for out-of-field recurrence. Although, a standardised follow-up protocol was not followed, all the studies employed serial prostate-specific antigen monitoring, a multiparametric magnetic resonance imaging, and a biopsy (6-12 months post-treatment). Across all the studies, 58% reported that the urinary continence returned to the pretreatment levels and 25% reported a minor decrease in the continence from the baseline at 12-months of follow-up. Erections sufficient for intercourse varied from 44% to 75% at the baseline to 55% to 100% at 12-months of follow-up across all the studies. Conclusion: IRE, as a focal therapy, shows promising results with minimal complications and reasonably effective oncological control, but the data comparing it to the standard of care is still lacking. Future research should focus on randomized definitive comparisons between IRE, radical prostatectomy, and radiation therapy.

Propensity score matched survival analysis of octogenarians with muscle-invasive bladder cancer: chemoradiation compared to radical cystectomy.

INTRODUCTION: Radical cystectomy (RC) is an effective curative treatment option for muscle-invasive bladder cancer (MIBC). However, chemoradiation (CRT) is an evolving bladder preservation protocol alternative to RC. With the increase in life expectancy, it is essential to understand the survival outcomes among octogenarians treated with RC and CRT. In this study, we use the National Cancer Database (NCDB) to compare the survival outcomes between RC and CRT in octogenarians. MATERIALS AND METHODS: We collected the data of patients treated for bladder cancer between 2004 to 2018 from the NCDB. Our primary analytic cohort included patients with MIBC (cT2-T4N0M0). We identified the octogenarians and categorized them into RC and CRT arms. The RC arm included those who received RC. The CRT arm included those who received chemotherapy within 90 days of curative radiation therapy. After 1:1 propensity score matching, overall survival (OS) outcomes were compared between both arms. RESULTS: Among the octogenarians, the median OS for patients treated with RC was 26.1 months (95% CI, 23.9-28.2), and CRT was 28.7 months (95% CI, 26.8-30.6). Our covariate analyses showed that academic institutions performed more RC (49% RC and 29.7% CRT) and community programs served more CRT (45.7% CRT and 24.2% RC). A multivariate Cox regression analysis showed that the mortality risk increased as the Charlson-Deyo comorbidity score and T stage increased. CONCLUSION: Octogenarians treated with RC and CRT had similar OS. As life expectancy increases, it is essential to individualize the treatment strategy based on risk assessment and its potential benefits.

Surgeon administered transversus abdominis plane block: anatomic principles and technique.

The Transversus Abdominis Plane (TAP) block is a regional abdominal wall block that has been effectively used as an adjunct to alleviate postoperative pain. The ultrasound-guided TAP (USTAP) administered by anesthesiologists is the gold standard and has been effective for surgeries involving abdominal wall incisions. Recently, the TAP block has been administered by surgeons with the help of direct visualization during minimally invasive surgery. The surgeon-administered or laparoscopic-guided TAP block has been compared to the USTAP with no discernible difference in patient outcomes. Also, directly visualizing the injection in the surgeon-administered block can offset complications such as visceral injury and block failure (injectate in the wrong plane). This review explores the literature's surgeon-administered TAP blocks for minimally invasive surgery in the literature. In addition, the prerequisite anatomy of the anterolateral abdominal wall, various approaches, and other factors that influence the efficacy of the block are described to increase awareness of this analgesic tool among surgeons and achieve better postoperative pain management.

A Novel Splice Variant of HYAL-4 Drives Malignant Transformation and Predicts Outcome in Patients with Bladder Cancer.

PURPOSE: Poor prognosis of patients with muscle-invasive bladder cancer that often metastasizes drives the need for discovery of molecular determinants of bladder cancer progression. Chondroitin sulfate proteoglycans, including CD44, regulate cancer progression; however, the identity of a chondroitinase (Chase) that cleaves chondroitin sulfate from proteoglycans is unknown. HYAL-4 is an understudied gene suspected to encode a Chase, with no known biological function. We evaluated HYAL-4 expression and its role in bladder cancer. EXPERIMENTAL DESIGN: In clinical specimens, HYAL-4 wild-type (Wt) and V1 expression was evaluated by RT-qPCR, IHC, and/or immunoblotting; a novel assay measured Chase activity. Wt and V1 were stably expressed or silenced in normal urothelial and three bladder cancer cell lines. Transfectants were analyzed for stem cell phenotype, invasive signature and tumorigenesis, and metastasis in four xenograft models, including orthotopic bladder. RESULTS: HYAL-4 expression, specifically a novel splice variant (V1), was elevated in bladder tumors; Wt expression was barely detectable. V1 encoded a truncated 349 amino acid protein that was secreted. In bladder cancer tissues, V1 levels associated with metastasis and cancer-specific survival with high efficacy and encoded Chase activity. V1 cleaved chondroitin-6-sulfate from CD44, increasing CD44 secretion. V1 induced stem cell phenotype, motility/invasion, and an invasive signature. CD44 knockdown abrogated these phenotypes. V1-expressing urothelial cells developed angiogenic, muscle-invasive tumors. V1-expressing bladder cancer cells formed tumors at low density and formed metastatic bladder tumors when implanted orthotopically. CONCLUSIONS: Our study discovered the first naturally-occurring eukaryotic/human Chase and connected it to disease pathology, specifically cancer. V1-Chase is a driver of malignant bladder cancer and potential predictor of outcome in patients with bladder cancer.

Clinical Utility of a Genomic Classifier in Men Undergoing Radical Prostatectomy: The PRO-IMPACT Trial.

PURPOSE: The optimal management of men with prostate cancer at high risk of recurrence postradical prostatectomy is controversial. The clinical utility of the Decipher test was evaluated prospectively on postoperative treatment decisions and patient-reported outcomes. METHODS AND MATERIALS: In the study, 246 eligible men across 19 centers were enrolled. Patients were dichotomized into those considering adjuvant or salvage radiation therapy (ART or SRT). Participating providers submitted a management recommendation before and after receiving the Decipher test results. Treatment received within 12 months and a validated survey on prostate cancer-related anxiety were collected longitudinally. RESULTS: Pre-Decipher, treatment was recommended for 12% and 40% for the ART and SRT arms, respectively. Post-Decipher, 17% and 30% of treatment recommendations changed in the ART and SRT arms, respectively. Post-Decipher treatment recommendation was administered 78% and 76% of the time in the ART and SRT arms, respectively. Multivariable analysis confirmed that the Decipher score was an independent predictor for change in management for both adjuvant and salvage patients. The number needed to test to change management for one patient was 4. Cancer-specific anxiety decreased among Decipher risk categories in both arms. CONCLUSIONS: Use of Decipher postradical prostatectomy test was associated with postoperative treatment decisions. Overall, high Decipher risk was associated with an increase in treatment intensity whereas low risk scores were associated with a decrease in therapy administered independent of clinical and pathologic risk factors.

Surgical Management of Organ-Confined Prostate Cancer with Review of Literature and Evolving Evidence.

Prostate cancer is the most common solid organ malignancy in men in the USA with an annual incidence of 105 and an annual mortality rate of 19 per 100,000 people. With the advent of PSA screening, the majority of prostate cancer diagnosed is organ confined. Recent studies including the SPCG-4 and PIVOT trials have demonstrated a survival benefit for those undergoing active treatment for localized prostate cancer. The foremost surgical option has been radical prostatectomy (RP). The gold standard has been open radical retropubic prostatectomy (RRP); however, minimally invasive approaches including laparoscopic and robotic approaches are commonplace and increasing in popularity. We aim to describe the surgical options for the treatment of localized prostate cancer by reviewing the literature. A review of the literature was undertaken using MEDLINE and PubMed. Articles addressing the topic of radical prostatectomy by open, laparoscopic and robotic approaches were selected. Studies comparing the different modalities were also identified. These articles were reviewed for data pertaining to perioperative, oncological and functional outcomes. There is a paucity of randomized studies comparing the three modalities. The published data has demonstrated a benefit in favour of robotically assisted laparoscopic prostatectomy (RALP) over laparoscopic radical prostatectomy (LRP) and traditional open RRP in perioperative outcomes. When reviewing the best-reported outcomes for RALP compared to LRP and RRP, operative times are lower (105 vs. 138 vs. 138 min), estimated blood loss rates are lower (111 vs. 200 vs. 300 ml) and blood transfusion rates are lower as in the length of stay (1 vs. 2 vs. 2.3 days) and overall complication rates (4.3 vs. 5 vs. 20%). Similarly, when reviewing functional outcomes, RALP compared to LRP was not inferior. At 12 months, the reported continence was 97 vs. 94 vs. 89% and potency was 94 vs. 77 vs. 90%. In comparative studies, however, these differences did not always meet statistical significance. With respect to oncological outcomes, there was no clear evidence of superiority of one modality over another. RALP is now the most common modality for surgical treatment of organ-confined prostate cancer. Individual series appear to support better perioperative outcomes and perhaps quicker return to functional outcomes. There does not appear to be a clear advantage to date in oncological parameters; however, RALP does not appear to be inferior to either LRP or RRP. It is anticipated that further high quality randomized studies will shed more light on the clinical and statistical significance in the comparison between these modalities.

Molecular Characterization of Renal Cell Carcinoma: A Potential Three-MicroRNA Prognostic Signature.

Background: Aberrantly expressed miRNAs promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach.Methods: Differentially expressed miRNAs were identified and analyzed in 113 specimens (normal kidney: 59; tumor: 54). miRNA profiling was performed in matched normal and tumor specimens from 8 patients and extended to 32 specimens. Seven aberrantly expressed miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n = 241).Results: Discovery phase identified miR-21, miR-142-3p, miR-142-5p, miR-150, and miR-155 as significantly upregulated (2-4-fold) and miR-192 and miR-194 as downregulated (3-60-fold) in RCC; miR-155 distinguished small tumors (<4 cm) from benign oncocytomas. In univariate and multivariate analyses, miRNA combinations (miR-21+194; miR-21+142-5p+194) significantly predicted metastasis and/or disease-specific mortality; miR-21+142-5p+194 (for metastasis): P = 0.0017; OR, 0.53; 95% confidence interval (CI), 0.75-0.33; 86.7% sensitivity; 82% specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21+142-5p+194: P < 0.0001; OR, 0.37; 95% CI, 0.58-0.23).Conclusions: The interconnected discovery-validation approach identified a three-miRNA signature as a potential predictor of disease outcome in RCC patients.Impact: With 10% survival at 5 years, metastatic disease presents poor prognosis for RCC patients. The three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis. Cancer Epidemiol Biomarkers Prev; 27(4); 464-72. ©2018 AACR.

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.

BACKGROUND: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. METHODS: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models. RESULTS: In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial-mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with ß-catenin, Twist and Snail expression, but negatively with E-cadherin expression. CONCLUSIONS: This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO-IMPACT study.

BACKGROUND: Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. METHODS: A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa-related anxiety. RESULTS: Before the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment recommendations changed in the ART arm, including 31% among high-risk patients; and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [P<.001]; SRT arm: median DCS before Decipher, 27 and after Decipher, 23 [P<.001]). PCa-specific anxiety changed after Decipher testing; fear of PCa disease recurrence in the ART arm (P = .02) and PCa-specific anxiety in the SRT arm (P = .05) decreased significantly among low-risk patients. Decipher results reported per 5% increase in 5-year metastasis probability were associated with the decision to pursue ART (odds ratio, 1.48; 95% CI, 1.19-1.85) and SRT (odds ratio, 1.41; 95% CI, 1.09-1.81) in multivariable logistic regression analysis. CONCLUSIONS: Knowledge of Decipher test results was associated with treatment decision making and improved decisional effectiveness among men with PCa who were considering ART and SRT. Cancer 2017;123:2850-59. © 2017 American Cancer Society.

Predictive models and risk of biopsy progression in active surveillance patients.

OBJECTIVE: To analyze the performance of different radical prostatectomy-based prognostic tools in predicting the biopsy progression in our active surveillance cohort. MATERIALS AND METHODS: We analyzed 326 patients with biopsy Gleason grade≤6,≤2 positive biopsy cores,≤20% tumor present in any core, prostate-specific antigen<15ng/dl, and clinical stages T1-T2a all of whom had at least single surveillance biopsy. Probabilities of pathologically relatively aggressive disease were estimated using Partin and Dinh risk tables and Kattan, Truong, and Kulkarni nomograms for each individual patient. Using these predictions, performance of these tools was quantified regarding discrimination, stratification at different cut-points, calibration, and the clinical net benefit. RESULTS: Predictions of Partin and Dinh tables were not associated with the biopsy progression. The predictive value of Kattan and Truong nomograms was higher when compared with the other tools, although it was significant only on the first and second surveillance biopsies. Both nomograms were able to identify low- and high-risk subgroups within the cohort. Kattan nomogram demonstrated better correlation with the observed rate of progression over the first 3 biopsies and higher clinical net benefit. CONCLUSION: Kattan and Truong nomograms demonstrated the best performance in predicting biopsy progression, although their value was largely limited to the first 2 surveillance biopsies. Both tools were able to stratify patients into subgroups with different risks of progression. These nomograms have important differences, which suggest that a more effective predictive model combining the strong sides of both tools and possibly some other variables could be developed.

Is It Time to Revisit the Role of Prostate-specific Antigen Kinetics in Active Surveillance for Prostate Cancer?

OBJECTIVE: To identify factors that are not available at the time of prostate cancer diagnosis and are associated with the risk of biopsy progression in active surveillance (AS) patients. MATERIALS AND METHODS: The study included 314 AS patients who had at least 1 repeat biopsy. We used logistic regression to analyze the association between prostate-specific antigen (PSA) and its derivatives, including PSA density, PSA velocity (PSAV) and doubling time (PSADT); presence of bilateral disease and number of previous successive negative surveillance biopsies; and the risk of progression on the surveillance biopsies first through fourth. RESULTS: Over a median follow-up of 3.1 years, patients had a mean of 2.4 biopsies. The median time from diagnosis to the last biopsy was 2.3 years. The biopsies were performed at fairly equal intervals. For surveillance biopsies 1 through 3, none of the studied factors was adding significant prognostic information to the baseline characteristics. PSAV and PSADT were associated with the risk of progression on the fourth biopsy; this association was independent of baseline characteristics. No progression on the fourth biopsy was noted in 23 patients with negative PSAV. Among 54 patients with PSADT of more than 3 years only, 2 progressed whereas 6 out of 9 patients with a PSADT less than 3 years had biopsy progression on the fourth surveillance biopsy. CONCLUSION: PSA kinetics may be helpful in defining the indications for prostate biopsy in AS patients who are followed with regular biopsies for more than 3-4 years.

Robotic Partial Nephrectomy with the Da Vinci Xi.

Purpose. The surgical expertise to perform robotic partial nephrectomy is heavily dependent on technology. The Da Vinci Xi (XI) is the latest robotic surgical platform with significant advancements compared to its predecessor. We describe our operative technique and experience with the XI system for robotic partial nephrectomy (RPN). Materials and Methods. Patients with clinical T1 renal masses were offered RPN with the XI. We used laser targeting, autopositioning, and a novel "in-line" port placement to perform RPN. Results. 15 patients underwent RPN with the XI. There were no intraoperative complications and no operative conversions. Mean console time was 101.3 minutes (range 44-176 minutes). Mean ischemia time was 17.5 minutes and estimated blood loss was 120 mLs. 12 of 15 patients had renal cell carcinoma. Two patients had oncocytoma and one had benign cystic disease. All patients had negative surgical margins and pathologic T1 disease. Two postoperative complications were encountered, including one patient who developed a pseudoaneurysm and one readmitted for presumed urinary tract infection. Conclusions. RPN with the XI system can be safely performed. Combining our surgical technique with the technological advancements on the XI offers patients acceptable pathologic and perioperative outcomes.

Prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in active surveillance patients.

OBJECTIVE: To analyze the association between prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in prostate cancer patients on active surveillance, and to study the effect of prediagnostic prostate-specific antigen values on the predictive performance of prostate-specific antigen velocity and prostate-specific antigen doubling time. METHODS: The study included 137 active surveillance patients with two or more prediagnostic prostate-specific antigen levels measured over a period of at least 3 months. Two sets of analyses were carried out. First, the association between prostate-specific antigen kinetics calculated using only the prediagnostic prostate-specific antigen values and the risk of biopsy progression was studied. Second, using the same cohort of patients, the predictive value of prostate-specific antigen kinetics calculated using only post-diagnostic prostate-specific antigens and compared with that of prostate-specific antigen kinetics based on both pre- and post-diagnostic prostate-specific antigen levels was analyzed. RESULTS: Of 137 patients included in the analysis, 37 (27%) had biopsy progression over a median follow-up period of 3.2 years. Prediagnostic prostate-specific antigen velocity of more than 2 ng/mL/year and 3 ng/mL/year was statistically significantly associated with the risk of future biopsy progression. However, after adjustment for baseline prostate-specific antigen density, these associations were no longer significant. None of the tested prostate-specific antigen kinetics based on combined pre- and post-diagnostic prostate-specific antigen values were statistically significantly associated with the risk of biopsy progression. CONCLUSIONS: Historical prediagnostic prostate-specific antigens seems to be not clinically useful in patients diagnosed with low-risk prostate cancer on active surveillance.

Epigenetics application in the diagnosis and treatment of bladder cancer.

INTRODUCTION: Bladder cancer is the sixth most common cancer in the Western world. Patients with bladder cancer require close monitoring, which may include frequent cystoscopy and urine cytology. Such monitoring results in significant health care cost. The application of epigenetics may allow for a risk adapted approach and more cost-effective method of monitoring. A number of epigenetic changes have been described for many cancer sites, including the urinary bladder. In this review, we discuss the use of epigenetics in bladder cancer and the potential diagnostic and therapeutic applications. MATERIALS AND METHODS: A comprehensive search of the English medical literature was conducted in PubMed using the terms microRNA regulation, DNA methylation, histone modification and bladder cancer. RESULTS: The most important epigenetic changes include DNA methylation, histone modification and microRNA regulation. Both DNA hypomethylation and hypermethylation have been associated with higher rate of cancer. The association of epigenetic changes with bladder cancer has led to the research of its diagnostic and prognostic implications as well as to the development of novel drugs to target these changes with the aim of achieving a survival benefit. CONCLUSIONS: Recently, epigenetics has been shown to play a much greater role than previously anticipated in the initiation and propagation of many tumors. The use of epigenetics for the diagnosis and treatment of bladder cancer is an evolving and promising field. The possibility of reversing epigenetic changes may facilitate additional cancer treatment options in the future.

The role of epigenetics in kidney malignancies.

INTRODUCTION: Renal cell carcinomas (RCC) are collectively the third most common type of genitourinary neoplasms, surpassed only by prostate and bladder cancer. Cure rates for renal cell carcinoma are related to tumor grade and stage; therefore, diagnostic methods for early detection and new therapeutic modalities are of paramount importance. Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself. Epigenetics may play an important role in the pursuit of early diagnosis, accurate prognostication and identification of new therapeutic targets. MATERIAL AND METHODS: We used PubMed to conduct a comprehensive search of the English medical literature using search terms including epigenetics, DNA methylation, histone modification, microRNA regulation (miRNA) and RCC. In this review, we discuss the potential application of epigenetics in the diagnosis, prognosis and treatment of kidney cancer. RESULTS: During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors. This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit. CONCLUSIONS: Epigenetics has become a promising field in cancer research. The potential to achieve early detection and accurate prognostication in kidney cancer might be feasible through the application of epigenetics. The possibility to reverse these epigenetic changes with new therapeutic agents motivates researchers to continue pursuing better treatment options for kidney cancer and other malignancies.

Operative technique and early experience for robotic-assisted laparoscopic nephroureterectomy (RALNU) using da Vinci Xi.

PURPOSE: Robotic-assisted laparoscopic nephroureterectomy (RALNU) has been previously utilized for management of upper tract urothelial carcinoma. The da Vinci Xi surgical system was released in April of 2014. We describe our operative technique and early experience for RALNU using the da Vinci Xi system highlighting unique features of this surgical platform. MATERIALS AND METHODS: A total of 10 patients with a diagnosis of upper tract urothelial carcinoma underwent RALNU using the da Vinci Xi system between April and November of 2014. A novel, oblique "in line" robotic trocar configuration was utilized to access the upper abdomen (nephrectomy portion) and pelvis (bladder cuff excision) without undocking. The port hopping feature of da Vinci Xi was utilized to facilitate optimal, multi-quadrant visualization during RALNU. RESULTS: Robotic-assisted laparoscopic nephroureterectomy was successfully completed without open conversion in all 10 patients. Mean operative time was 184 min (range 140-300 min), mean estimated blood loss was 121 cc (range 60-300 cc), and mean hospital stay was 2.4 days. Final pathology demonstrated high grade urothelial carcinoma in all patients. Surgical margins were negative in all patients. No intra-operative complications were encountered. One patient developed a pulmonary embolus after being discharged. No patients required a blood transfusion. Mean patient follow-up was 130 days (range 15-210 days). CONCLUSION: The use of da Vinci Xi with a novel, oblique "in line" port configuration and camera port hopping technique allows for an efficient and reproducible method for RALNU without the need for repositioning the patient or the robot during surgery.

Prognostic significance of cystoscopy findings following neoadjuvant chemotherapy for muscle-invasive bladder cancer.

INTRODUCTION: To evaluate the potential significance of cystoscopy findings following neoadjuvant chemotherapy (NAC) as prognostic indicator in patients undergoing radical cystectomy for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: Patients who received NAC prior to radical cystectomy for MIBC were analyzed. Patients were divided into two groups according to cystoscopy performed after two cycles of NAC: responders and non-responders. Univariate analysis was performed to analyze associations between observed response to chemotherapy and pT stage, pN stage and tumor downstaging. Logistic regression modeling was fitted to evaluate predictors for extravesical disease and pathologic downstaging. Kaplan-Meier analysis was used to evaluate disease specific survival. RESULTS: We identified 101 patients who received neoadjuvant chemotherapy prior to radical cystectomy. According to the cystoscopy findings, 60 patients (59%) were identified as responders to NAC. Stage pT0 at cystectomy was confirmed in 22 patients (36.5%) in the responder group versus only 1 patient (2.5%) in the non-responder group. Univariate analysis showed statistically significant association between response to chemotherapy observed on cystoscopy and pT stage as well as tumor downstaging. Multivariate regression modeling revealed that cystoscopy findings were an independent predictor of extravesical disease and pathologic downstaging. There was a distinct survival benefit in NAC responder group (p < 0.001). Cox proportional hazard model identified cystoscopy findings as an independent predictor of survival (OR 0.38, 95% CI 0.20-0.74, p = 0.004). CONCLUSIONS: Observed response to NAC on follow up cystoscopy is associated with favorable pathological outcomes and is a significant predictor of survival in patients undergoing radical cystectomy for MIBC.

Neoadjuvant Radiotherapy Improves Survival in Patients With T2b/T3 Bladder Cancer: A Population-Based Analysis.

BACKGROUND: Neoadjuvant radiotherapy (NART) for muscle-invasive bladder cancer (MIBC) is currently underused. However, the outcomes for MIBC have remained suboptimal. We investigated the relationship of NART to cause-specific mortality (CSM) and overall mortality (OM) among patients with a diagnosis of MIBC. MATERIALS AND METHODS: The patients diagnosed with primary invasive urothelial carcinoma of the bladder from 1983 to 2008 with localized disease were included. Patients aged > 90 years, those diagnosed with T1 or T4 BC, and those with no information on tumor grade were excluded from the analysis. Kaplan-Meier, Cox regression, and competing risk methods were used in the analysis of OM and CSM. RESULTS: A total of 5562 patients were included in the cohort (115 NART and 5447 surgery alone). On univariate analysis, NART significantly decreased the OM for patients with high-grade BC (hazard ratio [HR], 0.8), stage T2b (HR, 0.74), and stage T2b/T3 (HR, 0.74). CSM was also lower for those with stage T2b disease (HR, 0.63). Multivariable analysis revealed that NART was associated with a significant decrease in CSM (P = .043) and OM (P = .0462) for those with T2b. Likewise, an improvement was seen in OM (P = .0337) for patients with T2b/T3 who had received NART. CONCLUSION: NART was significantly associated with decreased CSM and OM in patients with clinical T2b/T3 BC and OM for patients with T2b/T3. These data suggest that NART could be beneficial in patients with T2b/T3 BC. In the modern era, the greatest utility would potentially be for patients with an incomplete response to neoadjuvant chemotherapy or as an adjunct to chemotherapy to improve the complete response rates.