Lentiviral interferon: A novel method for gene therapy in bladder cancer.

Interferon alpha (IFNα) gene therapy is emerging as a new treatment option for patients with non-muscle invasive bladder cancer (NMIBC). Adenoviral vectors expressing IFNα have shown clinical efficacy treating bacillus Calmette-Guerin (BCG)-unresponsive bladder cancer (BLCA). However, transient transgene expression and adenoviral immunogenicity may limit therapeutic activity. Lentiviral vectors can achieve stable transgene expression and are less immunogenic. In this study, we evaluated lentiviral vectors expressing murine IFNα (LV-IFNα) and demonstrate IFNα expression by transduced murine BLCA cell lines, bladder urothelium, and within the urine following intravesical instillation. Murine BLCA cell lines (MB49 and UPPL1541) were sensitive to IFN-mediated cell death after LV-IFNα, whereas BBN975 was inherently resistant. Upregulation of interleukin-6 (IL-6) predicted sensitivity to IFN-mediated cell death mediated by caspase signaling, which when inhibited abrogated IFN-mediated cell killing. Intravesical therapy with LV-IFNα/Syn3 in a syngeneic BLCA model significantly improved survival, and molecular analysis of treated tumors revealed upregulation of apoptotic and immune-cell-mediated death pathways. In particular, biomarker discovery analysis identified three clinically actionable targets, PD-L1, epidermal growth factor receptor (EGFR), and ALDHA1A, in murine tumors treated with LV-IFNα/Syn3. Our findings warrant the comparison of adenoviral and LV-IFNα and the study of novel combination strategies with IFNα gene therapy for the BLCA treatment.

Long-Term Outcomes of Whole Gland Salvage Cryotherapy for Locally Recurrent Prostate Cancer following Radiation Therapy: A Combined Analysis of Two Centers.

PURPOSE: Radiation refractory prostate cancer (RRPCa) is common and salvage cryotherapy for RRPCa is emerging as a viable local treatment option. However, there is a paucity of long-term data. The purpose of this study is to determine long-term outcomes following salvage cryotherapy for RRPca. MATERIALS AND METHODS: Patients undergoing salvage cryotherapy for biopsy-proven, localized RRPCa from 1992 through 2004 were prospectively accrued at two centers. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from our database. The primary outcomes were overall survival (OS) and disease-specific survival (DSS). The secondary outcomes were freedom from castration-resistant prostate cancer (CRPC) and freedom from androgen deprivation therapy (ADT). RESULTS: A total of 268 patients were identified with a median followup of 10.3 years. A total of 223 complication events were recorded; of them, 168 were Clavien I-II events and 55 Clavien III events. At 10 years, 69% had freedom from ADT and 76% had freedom from CRPC. The 10-year DSS rate was 81%, and the 10-year OS rate was 77%. A pre-salvage prostate specific antigen level of >10 ng/ml was associated with an increased risk of developing CRPC and initiation of ADT but was not associated with DSS or OS. The use of neoadjuvant ADT was associated with improved OS and DSS but did not affect freedom from CRPC or adjuvant ADT. CONCLUSIONS: Salvage cryotherapy for RRPCa provides excellent long-term freedom from ADT, CRPC and DSS with acceptable morbidity. OS at 10 years was 77%. Prospective trials are required for validation.

Cost-Effectiveness of Robot-assisted Radical Cystectomy Using a Propensity-matched Cohort.

BACKGROUND: Health-related quality of life is important for patients undergoing radical cystectomy (RC). OBJECTIVE: To determine the cost-effectiveness of robotic-assisted RC (RARC) compared to open cystectomy (OC) for bladder cancer and factors that contribute to cost-effectiveness. DESIGN, SETTING, AND PARTICIPANTS: A decision analytic model was used to compare health-related quality of life and medical costs for RARCs with intracorporeal urinary diversion and OCs performed between 2007 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Propensity matching was performed among 1322 cases to yield a final cohort of 100 RARC and 96 ORC cases. Probabilities were obtained from the clinical study data, while quality-adjusted life years (QALYs) and health utility values were derived from the literature. A complication, readmission, or transfusion was included in the 90-d time horizon model. RESULTS AND LIMITATIONS: There were no differences between the groups in patient demographics, pathologic staging, or length of stay. Multivariable analysis revealed that the RARC group had fewer transfusions and complications compared to the OC group. The incremental cost-effectiveness ratio was $2969. RARC cost $2969 less per QALY when compared to OC. While RARC was $17000 more expensive, it also associated with an increase of 0.32 QALYs. One-way sensitivity analysis identified RARC as the preferred strategy if a complication can be prevented 74% of the time. RARC is preferred as long as it is 70% effective in preventing a transfusion. Two-way sensitivity analysis showed that as long as RARC can prevent complications and transfusions, it is the preferred cost-effective treatment when compared to OC. The study is limited by the omission of a societal perspective and the lack of health utility values for RC. CONCLUSIONS: RARC is cost-effective compared to OC when the rates of complications and transfusions are significantly lower. PATIENT SUMMARY: Bladder removal via a robotic approach is more expensive, but it improves health-related quality of life. Robotic surgery is cost-effective compared to an open approach for bladder removal if there are low rates of complications and blood transfusion.

Using Grade of Recurrent Tumor to Guide Further Therapy While on Bacillus Calmette-Guerin: Low-grade Recurrences Are not Benign.

BACKGROUND: Tumors that recur after bacillus Calmette-Guerin (BCG) therapy are considered to be of very high risk, and patients are often recommended to undergo radical cystectomy (RC). However, the nuances associated with the grade of tumor recurrence after BCG treatment are not well understood. OBJECTIVE: To characterize the pattern of bladder cancer progression and cancer-specific survival (CSS) in patients with recurrences dichotomized by low grade (LG) versus high grade (HG) after intravesical BCG treatment, and to assess the safety of continued bladder-sparing therapy in these patients. DESIGN, SETTING, AND PARTICIPANTS: We performed an Institutional Review Board-approved review of our bladder cancer database. Overall, 146 non-muscle-invasive bladder cancer (NMIBC) patients were found to have NMIBC recurrence while on BCG therapy; this recurrence was LG in 38 and HG in 108. Baseline clinicopathologic characteristics including age, gender, primary tumor grade, stage, size, multiplicity, and concurrent carcinoma in situ were also evaluated. The primary endpoint was progression-free survival (PFS), with progression defined as the development of muscle-invasive bladder cancer (MIBC)/distant metastasis. In addition, recurrence-free survival (RFS), HG RFS, cystectomy-free survival (CFS), and CSS were also compared. Multivariable analysis was performed using the Cox regression model. All tests were two sided, and p<0.05 was considered statistically significant. INTERVENTION: Further intravesical therapy versus salvage RC. RESULTS AND LIMITATIONS: Overall, estimated 5-yr PFS was 72.4% (95% confidence interval [CI] 60.4-81.3%). As dichotomized by grade of recurrent tumor, PFS was greater for patients with LG recurrences (85.6%, 95% CI 60.8-95.2%) than for those with HG recurrence (67.9%, 95% CI 54.1-78.4%; p=0.010). Furthermore, patients whose initial recurrence on BCG therapy was LG had improved subsequent RFS (median 62 vs 34mo, p=0.007), HG RFS (median 112 vs 36mo, p<0.001), and CFS (estimated 5-yr CFS 80.8% vs 49.8%, p<0.001) compared with those who had HG initial recurrence. On univariate and multivariate analyses, grade of tumor recurrence after BCG was an independent predictor of time to progression to MIBC/distant metastasis (hazard ratio 3.60, 95% CI 1.18-10.94, p=0.024). CONCLUSIONS: Grade of tumor recurrence after intravesical BCG is an important predictor of bladder cancer progression to MIBC/metastatic urothelial carcinoma. While, patients with LG recurrences have less than half the progression events compared with those with HG recurrences, their estimated 5-yr progression rate is still 14.4%. Hence all patients should be carefully counseled on bladder-sparing therapy. This also has implications for clinical trial design. PATIENT SUMMARY: If bladder cancer recurs after bacillus Calmette-Guerin treatment, there are many factors that determine the further clinical outcome. Although low-grade recurrent tumors confer a less aggressive course, disease progression can still occur, and hence continued vigilance is important.

Salvage topical therapy for upper tract urothelial carcinoma.

PURPOSE: Topical therapy (TT) for upper tract urothelial carcinoma (UTUC) has been explored as a kidney sparing approach to treat carcinoma in situ (CIS) and as adjuvant for endoscopically treated Ta/T1 tumors. In bladder cancer, data support use of salvage TT for repeat induction. We investigate the outcomes of salvage TT for UTUC in patients ineligible for or refusing nephroureterectomy. METHODS: A single-center retrospective review on patients receiving salvage TT via percutaneous nephrostomy tube or cystoscopically placed ureteral catheters was performed. Primary outcome was response to therapy based on International Bladder Cancer Group criteria. RESULTS: 51 patients with 58 renal units (RUs) received TT. Of these, 17 patients with 18 RUs received the second-line TT, with a median follow-up of 36.5 months (IQR 24.5-67 months). 44% (8/18) received salvage TT for refractory disease and 56% (10/18) as reinduction. 5 RUs with CIS were unresponsive to initial TT and went on to receive salvage TT, of which 20% (1/5) responded. 13 RUs recurred or relapsed following initial TT and received salvage TT for papillary tumors, with 62% (8/13) responding. CONCLUSION: Our data provide preliminary clinical rationale for the second-line TT for refractory and recurrent, endoscopically managed papillary UTUC in patients ineligible for or refusing nephroureterectomy. However, refractory upper tract CIS appears to have poor response to salvage TT.

Oncologic outcomes of patients with positive surgical margin after partial nephrectomy: a 25-year single institution experience.

PURPOSE: To evaluate oncologic outcomes and management of patients with microscopic positive surgical margin (PSM) after partial nephrectomy (PN) for renal cell carcinoma (RCC). METHODS: We reviewed our database to identify patients who underwent PN between 1990 and 2015 for RCC and had PSM on final pathology. A 1:3 matching was performed to a negative surgical margin (NSM) cohort. Kaplan-Meier method and log-rank test were used to estimate survival and differences in outcomes, respectively. Cox proportional hazards models were conducted to estimate the Hazards ratio. RESULTS: A total of 2297 patients underwent PN at our institution, of which 1863 (81%) had RCC. Microscopic PSM was found in 34 (1.8%) RCC patients who were matched to 100 patients with NSM. Of these 34 patients, local recurrence (n = 4), distant kidney recurrences (n = 4), and metastases (n = 5) developed during a median follow-up of 62 months. Bilateral tumors/tumors in a solitary kidney (n = 12/13, 92%), and multifocal tumors (n = 7/13, 54%) were found in patients who developed recurrence/metastasis. PSM patients were at a higher risk of shorter overall survival (p = 0.001), local recurrence-free survival (p = 0.003), distant recurrence-free survival (p = 0.032) and metastasis-free survival (p = 0.018). There was statistically significant association between PSM and bilateral tumors, prior treated RCC at presentation and higher nephrometry score in multivariable model. CONCLUSIONS: There was a low rate of microscopic PSM in our large cohort of patients undergoing PN despite tumor complexity. Higher nephrometry score, bilateral tumors, and prior treated RCC independently predicted PSM which showed worse survival, recurrence and metastasis compared to patients with NSM.

Intraoperative Conversion From Partial to Radical Nephrectomy: Incidence, Predictive Factors, and Outcomes.

OBJECTIVE: To evaluate preoperative and intraoperative predictors of conversion to radical nephrectomy (RN) in a cohort of patients undergoing a planned partial nephrectomy (PN) for renal cell carcinoma (RCC). METHODS: A single-center, retrospective review was conducted using our PN database that includes patients who were scheduled to undergo PN (regardless of the approach) but were converted to RN between August 1990 and December 2016. Reasons for conversion were collected from the operative report. Patient demographics and perioperative variables were compared with the successful PN group. Univariate and multivariate logistic regression analyses were conducted to assess predictors of conversion. RESULTS: A total of 1857 patients were scheduled to undergo PN. Of these patients, 90 (5%) were converted to RN. The multivariate model showed that larger tumor size (odds ratio [OR] = 1.20, P = .040), higher RENAL nephrometry score (OR = 1.41, P = .001), hilar tumor or renal sinus invasion (OR = 2.80, P = .004), laparoscopic PN (OR = 7.34, P <.001), intraoperative bleeding (OR = 19.62, P <.001), positive surgical margin (OR = 31.85, P <.001), and advanced pathologic tumor-stage (T3 or T4) (OR = 7.29, P <.001) were associated with increased odds of intraoperative conversion to RN. CONCLUSION: The rate of conversion to RN was low in patients who were scheduled to undergo PN in this series. Larger tumor size with increasing complexity, hilar tumor location or renal sinus invasion, locally advanced tumors, laparoscopic PN but not robotic PN, bleeding complication, and positive surgical margin were associated with intraoperative conversion from scheduled PN to RN.

Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma.

PURPOSE: Patients with Lynch syndrome are at risk for upper tract urothelial carcinoma. We sought to identify the incidence and most reliable means of point of care screening for Lynch syndrome in patients with upper tract urothelial carcinoma. MATERIALS AND METHODS: A total of 115 consecutive patients with upper tract urothelial carcinoma without a history of Lynch syndrome were universally screened during followup from January 2013 through July 2016. We evaluated patient and family history using AMS (Amsterdam criteria) I and II, and tumor immunohistochemistry for mismatch repair proteins and microsatellite instability. Patients who were positive for AMS I/II, microsatellite instability or immunohistochemistry were classified as potentially having Lynch syndrome and referred for clinical genetic analysis and counseling. Patients with known Lynch syndrome served as positive controls. RESULTS: Of the 115 patients 16 (13.9%) screened positive for potential Lynch syndrome. Of these patients 7.0% met AMS II criteria, 11.3% had loss of at least 1 mismatch repair protein and 6.0% had high microsatellite instability. All 16 patients were referred for germline testing, 9 completed genetic analysis and counseling, and 6 were confirmed to have Lynch syndrome. All 7 patients with upper tract urothelial carcinoma who had a known history of Lynch syndrome were positive for AMS II criteria and at least a single mismatch repair protein loss while 5 of 6 had high microsatellite instability. CONCLUSIONS: We identified 13.9% of upper tract urothelial carcinoma cases as potential Lynch syndrome and 5.2% as confirmed Lynch syndrome at the point of care. These findings have important implications for universal screening of upper tract urothelial carcinoma, representing one of the highest rates of undiagnosed genetic disease in a urological cancer.

Effects of thiazolidinedione in patients with active bladder cancer.

OBJECTIVE: To examine the influence of perioperative thiazolidinedione (TZD) on cancer-specific outcomes in patients with diabetes mellitus (DM) undergoing radical cystectomy (RC) for urothelial carcinoma (UC). PATIENTS AND METHODS: A retrospective cohort of 173 patients with DM undergoing RC from 2005 to 2010 was identified. Of those, 53 were on TZD treatment at the time of RC, with 33 patients taking pioglitazone. Baseline clinicopathological characteristics, as well as cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were compared between the patients on and off TZD therapy at the time of RC. In subgroup analysis, outcomes in patients specifically taking pioglitazone at the time of RC were compared to those not on a TZD. RESULTS: Baseline clinicopathological characteristics were similar between patients on and off TZD therapy at the time of RC. Overall, the median CSS rate was not reached in either group (P = 0.7). The estimated 5-year CSS was 67.8% in the non-TZD group and 66.3% in the TZD group. On multivariate analysis incorporating patient age, pathological T-staging, and adjuvant chemotherapy, TZD use was found not to be a significant predictor for CSS (hazard ratio 1.20, 95% confidence interval 0.66-2.17; P = 0.5). Additionally, RFS (P= 0.3) and OS (P = 0.2) were also similar between the two groups without adjusting for other variables. Comparison between patients taking pioglitazone vs patients not taking TZD yielded similar CSS (P = 0.2), RFS (P = 0.5), and OS (P= 0.2). CONCLUSIONS: CSS, as well as RFS and OS after RC were not compromised in patients on TZD therapy at the time of RC. Additional investigation is warranted in patients with non-muscle-invasive bladder cancer and muscle-invasive bladder cancer undergoing bladder-sparing procedures to assess the safety of using TZD in the setting of active UC.

Salvage prostatectomy for post-radiation adenocarcinoma with treatment effect: Pathological and oncological outcomes.

INTRODUCTION: Prostate biopsies following localized radiation therapy for prostate cancer often demonstrate residual prostatic carcinoma with treatment effect (CTE). The final oncological outcome of prostatic CTE is currently uncertain. We studied the pathological and oncological outcomes for a large cohort of patients who had CTE on post-radiation therapy biopsy and subsequently underwent salvage radical prostatectomy (SRP). METHODS: A single-centre retrospective review of all SRPs performed from 1995-2014 was performed. Cases were selected for this analysis if they had had a post-radiation "for-cause" biopsy. Biopsy results were compared to final pathology results following SRP. Pathological and clinical outcomes were compared by extent of treatment effect seen on the post-radiation biopsy. RESULTS: A total of 70 patients who had salvage prostatectomy at MD Anderson Cancer Centre from 2007-2015 met study criteria. CTE was found on biopsy in the absence of other adenocarcinoma in 16 patients. Among them, one (7%) patient had no evidence of carcinoma at the time of salvage prostatectomy, four (27%) had CTE, three (20%) had adenocarcinoma with minimal or partial treatment effect (PTE), and seven (47%) had adenocarcinoma with no treatment effect (NTE). For those with CTE on biopsy, 69% had biochemical recurrence at a median time of 0.4 years (interquartile range [IQR] 0.22-1.52) vs. 52% for all patients (median 0.44 years, IQR 0.11-1.70) and 47% for those with no treatment effect (median 0.62 years, IQR 0.05-1.90). Metastasis developed after salvage prostatectomy in 11.8% of the whole cohort (8/68, median time to metastasis was 3.03 years, IQR 2.45-4.47), 26.7% of patients with CTE (median 3.2 years, IQR 1.96-4.44), and 6.7% of patients with NTE (median 2.45 years, IQR 0.98-2.86). Median recurrence-free survival was 2.78 years (95% confidence interval [CI] 0.84-5.43) for all patients, 0.51 years (95% CI 0.22-2.35) for those with CTE, and 4.95 years (95% CI 0.95-7.08) for those with NTE; the difference was not significant (p=0.13). On multivariate analysis, pre-SRP biopsy Gleason grade <7 (hazard ratio [HR] 0.38; 95% CI 0.14-1.02) and number of biopsy cores positive for carcinoma (HR 1.11; 95% CI 1.00-1.22) were significant for prediction of cancer recurrence. CONCLUSIONS: Patients undergoing salvage prostatectomy for CTE or PTE demonstrated in a for-cause biopsy after radiation therapy had pathological evidence of viable, untreated cancer in more than 50% of cases and were at significant risk of adverse pathological features. Patients with CTE may therefore benefit from salvage radical prostatectomy. Our study is limited by its retrospective nature and sample size. More studies are required to further validate our findings and assess the benefit of SRP in this population.

Impact of High-risk Features and Effect of Neoadjuvant Chemotherapy in Urothelial Cancer Patients with Invasion into the Lamina Propria on Transurethral Resection in the Absence of Deep Muscle Invasion.

BACKGROUND: High-risk non-muscle-invasive bladder cancer (NMIBC) that invades into the lamina propria is frequently understaged and is associated with a risk of lymph node metastasis and death. OBJECTIVE: To identify high-risk features (HRFs) for NMIBC that may identify patients with poorer prognosis who may benefit from neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: We performed a single-center retrospective review of patients who underwent RC for NMIBC with invasion into the lamina propria between 1995 and 2013. HRFs included hydronephrosis, abnormal examination under anesthesia, lymphovascular invasion, or variant histology. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology at RC, and overall (OS) and disease-specific (DSS) survival were evaluated and analyzed by Fisher's exact test, Student t test, Cox proportional hazards regression analysis, and the Kaplan-Meier method. RESULTS AND LIMITATIONS: We identified 336 patients with a median follow-up of 130 mo. Of these, 159 (47%) had no HRF, 140 (41.5%) had one HRF, and 37 (11%) had ≥2 HRFs. At RC, patients with ≥2 HRFs had a significantly higher rate of pathologic T stage upstaging and lymph node metastasis (p<0.05). Median OS was 139 mo for those with no HRF, 127 mo for those with one HRF, and 56 mo for those with ≥2 HRF (p=0.0057). HRFs are also associated with a decreased DSS (p=0.0009). Patients with ≥2 HRFs (11/37) who received NAC showed improved OS (21% vs 55% 5-yr OS, p=0.0353) and trended toward an improvement in DSS (25% vs 56% 5-yr OS, p=0.0716) compared with RC alone. CONCLUSIONS: The presence of ≥2 HRFs in NMIBC invading the lamina propria is associated with worse pathology at RC and a significant decrease in OS and DSS. NAC appears to provide benefit for these patients. Limitations include retrospective design and limited sample size. PATIENT SUMMARY: The presence of high-risk features in urothelial cancer with invasion into the lamina propria has a worse prognosis that may be mitigated by neoadjuvant chemotherapy.

Solubilization and Stability of Mitomycin C Solutions Prepared for Intravesical Administration.

BACKGROUND: Mitomycin C (MMC) is an antitumor agent that is often administered intravesically to treat bladder cancer. Pharmacologically optimized studies have suggested varying methods to optimize delivery, with drug concentration and solution volume being the main drivers. However, these MMC concentrations (e.g. 2.0 mg/mL) supersede its solubility threshold, raising major concerns of inferior drug delivery. OBJECTIVE: In this study, we seek to confirm that the pharmacologically optimized MMC concentrations are achievable in clinical practice through careful modifications of the solution preparation methods. METHODS: MMC admixtures (1.0 and 2.0 mg/mL) were prepared in normal saline using conventional and alternative compounding methods. Conventional methodology resulted in poorly soluble solutions, with many visible particulates and crystallates. However, special compounding methods, which included incubation of solutions at 50 °C for 50 min followed by storage at 37 °C, were sufficient to solubilize drug. Chemical degradation of MMC solutions was determined over 6 h using high-performance liquid chromatography (HPLC) analytics, while physical stability was tested in parallel. RESULTS: Immediately following the 50 min incubation, both MMC solutions exhibited approximately 5-7% drug degradation. Based on the measured concentrations and linear regression of degradation plots, additional storage of these solutions at 37 °C for 5 h retained chemical stability criterion (< 10% overall drug loss). No physical changes were observed in any solutions at any test time points. CONCLUSION: We recommend that the described alternative preparation methods may improve intravesicular delivery of MMC in this urological setting, and advise that clinicians employing these changes should closely monitor patients for MMC toxicities and pharmacodynamics (change in clinical outcomes) that result from the potential enhancement of MMC exposure in the bladder.

Role of radical prostatectomy in metastatic prostate cancer: A review.

CONTEXT: Recent demonstration of efficacy with the use of chemohormonal therapy for men with metastatic prostate cancer (mPCa) has expanded the therapeutic options for these patients. Furthermore, multimodal therapy to treat systemic disease in the context of locoregional control has gained increasing interest. Concomitantly, the role of radical prostatectomy (RP) in multimodal treatment for locally advanced prostate cancer is expanding. As a result, there is interest in investigating the potential benefit of cytoreductive RP in mPCa. OBJECTIVE: To review the literature regarding the role of cytoreductive prostatectomy in the setting of mPCa. EVIDENCE ACQUISITION: MEDLINE and PubMed electronic databases were queried for English language articles related to patients with mPCa who underwent RP from January 1990 to June 2016. Key words used in our search included cytoreductive prostatectomy, radical prostatectomy, and metastatic prostate cancer. Preclinical, retrospective, and prospective studies were included. EVIDENCE SYNTHESIS: There are no published randomized control trials examining the role of cytoreduction in mPCa. Local symptoms are high in mPCa and often provide a necessity for palliative procedures with the impact on oncologic outcomes being uncertain. Recently, preclinical and retrospective population-based data suggest a benefit from treatment of the primary tumor in metastatic disease. Potential mechanisms mediating this benefit include prevention of symptomatic local progression and modulation of disease biology, resulting in an improvement in progression-free and overall survival. Current literature supports the feasibility of cytoreductive prostatectomy as it is associated with acceptable side effects that are comparable to RP for high-risk localized disease. In aggregate, these data compel prospective evaluation of the hypothesis that cytoreductive prostatectomy improves the outcome of men with mPCa. CONCLUSIONS: Cytoreductive prostatectomy in mPCa is a feasible procedure that may improve outcomes for men when combined with multimodal management. Preclinical, translational, and retrospective evidence supports local therapy for metastatic disease. However, currently, evidence is limited and is subject to bias. The results of ongoing prospective randomized trials are required before incorporating this therapeutic strategy into clinical practice.

Assessing Symptom Burden in Bladder Cancer: An Overview of Bladder Cancer Specific Health-Related Quality of Life Instruments.

Background: A key component to monitoring and investigating patient QOL is through patient reported health related quality of life (HRQOL) outcome measures. Many instruments have been used to assess HRQOL in bladder cancer and each instrument varies in its development, validation, the context of its usage in the literature and its applicability to certain disease states. Objective: In this review, we sought to summarize how clinicians and researchers should most appropriately utilize the available HRQOL instruments for bladder cancer. Methods: We performed a comprehensive literature search of each instrument used in bladder cancer, paying particular attention to the outcomes assessed. We used these outcomes to group the available instruments into categories best reflecting their optimal usage by stage of disease. Results: We found 5 instruments specific to bladder cancer, of which 3 are validated. Only one of the instruments (the EORTC-QLQ-NMIBC24) was involved in a randomized, prospective validation study. The most heavily used instruments are the EORTC-QLQ-BLM30 for muscle-invasive disease and the FACT-Bl which is used across all disease states. Of the 5 available instruments, 4 are automatically administered with general instruments, while the BCI lacks modularity, and requires co-administration with a generalized instrument. Conclusion: There are multiple strong instruments for use in gauging HRQOL in bladder cancer patients. We have divided these instruments into three categories which optimize their usage: instruments for use following NMIBC treatments (EORTC-QLQ-NMIBC24), instruments for use following radical cystectomy (FACT-Bl-Cys and EORTC-QLQ-BLM30) and more inclusive instruments not limited by treatment modality (BCI and FACT-Bl).

New discoveries in the molecular landscape of bladder cancer.

We are currently on the cusp of exponential growth in the understanding of the molecular landscape of bladder cancer. Emerging data regarding the mutational burden and targetable genomic and protein alterations in bladder cancer have allowed us to tap into treatments directed toward specific molecular characteristics of bladder cancer. In parallel, these developments will enable us to better select patients for existing treatments of bladder cancer in a step toward personalized therapy. The present article reviews select discoveries that have advanced our understanding of bladder cancer and gives a glimpse of the exciting opportunities on the not-so-distant horizon.

A standardized protocol for identifying and counting lymph nodes harvested by pelvic lymph node dissection at the time of radical cystectomy.

INTRODUCTION: Lymph node counts have become a surrogate measure for the extent and quality of pelvic lymph node dissection (PLND) at radical cystectomy, but little consideration has been given to the methodology of lymph node processing. We report results from a prospective series comparing a conventional protocol for processing PLND specimens to a fat-emulsifying protocol. We hypothesized that the rate of node positivity would increase with the fat-emulsifying protocol. METHODS: Patients undergoing radical cystectomy for cTis-T4aN0-1M0 urothelial carcinoma of the bladder were eligible for this trial. Palpable lymph nodes were isolated from the PLND specimens in the conventional protocol. The remaining tissue was then processed with fat-emulsifying solution to identify further nodes visually. Nodal counts were compared between techniques. RESULTS: The median number of nodes counted in the PLND specimens of 26 patients was 24.5 (range: 20-40) with conventional processing and 37 (range: 24-52) with the fat-emulsifying solution (p < 0.001). Three patients had lymph node positive disease detected by conventional means, and a single patient was found to have a single positive node by the fat-emulsifying solution alone. The study was closed early after conducting a futility analysis. CONCLUSIONS: A fat-emulsifying protocol identified more lymph nodes than a conventional protocol and may be an appropriate method to standardize lymph node processing following PLND. However, we were unable to show that such a standardized approach significantly increased the rate of node positivity in patients undergoing radical cystectomy.

The use of TPA in combination with alcohol in the treatment of the recurrent complex hydrocele.

A hydrocele is an abnormal collection of serous fluid in the space between the parietal and visceral layers of the tunica vaginalis. Hydrocele is the most common cause of painless scrotal swelling which affects about 1% of men. Generally, adult hydroceles are idiopathic in origin; however, inguinal surgery, varicocelectomy, infection, trauma and a patent processus vaginalis are each associated with the subsequent development of a hydrocele. Surgical removal of hydroceles is the gold standard of care. However, multiple cases have reported high success rates (ranging from 85% to 96%) using a combination of aspiration and sclerotherapy. We present a case of a patient with recurring complex hydrocele and effective treatment utilizing a combination of thrombolytic therapy, catheter drainage and subsequent alcohol ablation.

Risk factors and outcomes for the development of malignancy in lung and heart-lung transplant recipients.

BACKGROUND: Many factors may limit survival from lung and heartlung transplantation, including malignancy. OBJECTIVE: To investigate factors associated with the development of malignancy following transplantation and its effect on survival by retrospectively reviewing a population of lung transplant recipients. METHODS: Data from 342 consecutive lung transplant patients were collected. Results were analyzed by fitting variables into a multivariate logistic regression model predicting the development of post-transplant malignancies. Covariates were selected based on crude associations that reached a level of significance at P ≤ 0.10. Length of survival was analyzed using the Kaplan-Meier method. RESULTS: Fifty-eight subjects developed post-transplant malignancies, which were the cause of death of 14 patients. Twenty-one patients had a pretransplant malignancy, of whom six developed a malignancy posttransplant--of these, two were fatal recurrences. No risk factors were significantly associated with all forms of post-transplant malignancy. When adjusted for age at transplantation and donor smoking history, Epstein-Barr virus seropositivity at the time of transplant was significantly associated with a reduced risk of a post-transplant lymphoproliferative disorder (OR 0.17; 95% CI 0.05 to 0.59). The median survival time in individuals without a post-transplant malignancy was significantly shorter than in those with a post-transplant malignancy (P = 0.018 Wilcoxon [Breslow]). This may be secondary to the length of time required to develop malignancy and the fact that not all malignancies that developed were fatal. The median time to develop malignancy was greater than two years. In addition, the 14 patients who died as a result of their malignancy had a significantly shorter survival time than the 44 who died because of nonmalignant causes (P < 0.001). CONCLUSIONS: Malignancy was not associated with an overall decrease in survival time when compared with those who did not develop a malignancy. Risk factors specific for the development of malignancies remain difficult to specify.