Surgical salvage in patients with advanced testicular cancer: indications, risks and outcomes

The purpose of this review is to present a comprehensive and updated review of the literature and summary of the indications, risks and outcomes related to salvage, desperation and late relapse surgery for advanced testicular cancer. After completing a thorough review of the current literature, this review has attempted to provide an overview of the indications for salvage, desperation and late relapse retroperitoneal lymph node dissection (RPLND) followed by a summary of the histopathologic and clinical outcomes regarding each. Recent literature, combined with a significant contribution from historical studies suggest that while testicular cancer is a relatively uncommon malignancy overall, it represents the most common solid organ malignancy for young men. Although a significant number of men are cured with a combination of first-line treatments, the remaining men are a diverse and often challenging cohort who require the benefit of expertise to improve their outcomes. The role of surgical strategies in the salvage, desperation and late relapse settings is unquestionable, although the most important question remains who will benefit. This often requires a multi-disciplinary approach at centers specializing in this disease process in order to recognize who should get surgery, what surgery to do and how to minimize the potential morbidity associated with the operation

Disparities in prostate cancer treatment associated with population density of the county of residence.

117 Background: We sought to assess disparities in primary treatment of prostate cancer by examining the effect of population density of the county of residence on treatment for clinically localized prostate cancer and quantify variation in primary treatment attributable to county and SEER site. Methods: Participants included 138,226 men with clinically localized prostate cancer who underwent surgery, radiation, or conservative therapy in the Surveillance, Epidemiology, and End Result (SEER) database diagnosed in 2005 through 2008. Mixed effects hierarchical logit models were used to examine the effect of population density of the county of residence on treatment while accounting for the random effects of counties nested within SEER sites. In order to quantify the effect of county and SEER site on individual treatment, the percent of total variance in treatment attributable to county of residence and SEER site was estimated with residual intraclass correlation coefficients. Results: Men in metropolitan counties had 23% higher odds of being treated compared with men in rural counties, controlling for number of urologists per county as well as patient clinical and sociodemographic characteristics. Age, race/ethnicity, PSA at diagnosis, and tumor characteristics were also significant predictors of treatment in the multivariable model. The percent of variation in treatment attributable to the county of residence was consistently higher than that attributable to SEER site. 3% (95% CI: 1.2%-6.2%) of the total variation in treatment was attributable to SEER site, while 6% (95% CI: 4.3%-9.0%) of variation was attributable to county of residence, controlling for clinical and sociodemographic characteristics. This variation at the county and SEER site increased to 4% and 10%, respectively, when specific type of treatment (surgery or radiation) was assessed. Conclusions: Variation in treatment for localized prostate cancer exists for men living in different population dense counties of the country. These findings highlight the need for comparative effectiveness research and health policy initiatives to advance prostate cancer research and reduce disparities in current clinical practice

A novel preoperative model to predict 90-day surgical mortality in patients considered for renal cell carcinoma surgery

Introduction Surgical benefits for renal cell carcinoma must be weighed against competing causes of mortality, especially in the elderly patient population. We used a large cancer registry to evaluate the impact of patient and cancer-specific factors on 90-day mortality (90DM). A nomogram to predict the odds of short-term mortality was created. Materials and Methods The National Cancer Database was queried to identify all patients with clinically localized, nonmetastatic disease treated with partial or radical nephrectomy. Using a random sample of 60%, multiple logistic regression with 90DM outcomes were performed to identify preoperative variables associated with mortality. Variables included age, sex, race, co-morbidity score, tumor size, and presence of a thrombus. A nomogram was created and tested on the remaining 40% of patients to predict 90DM. Results 183,407 patients met inclusion criteria. Overall 90DM for the cohort was 1.9%. All preoperative variables significantly influenced the risk of 90DM. Patient age was by far the strongest predictor. Nomogram scores ranged from 0 to 12. Compared to patients with 0 to 1 points, those with 2 to 3 (odds ratio [OR] 2.89, 2.42–3.46; P 6 (OR 12.86, 10.83–15.27; P 80 years of age alone placed patients into the highest risk of surgical mortality. Conclusions Management of localized kidney cancer must consider competing causes of mortality, especially in elderly patients with multiple co-morbidities. We present a preoperative tool to calculate risk of surgical short-term mortality to aid surgeon–patient counseling

Preadmission antidepressant use and bladder cancer: a population-based cohort study of stage at diagnosis, time to surgery, and surgical outcomes

BACKGROUND: Among cancer patients, prior antidepressant use has been associated with impaired survival. This could be due to differences in stage at diagnosis, in receipt of treatment, or in treatment complications. The purpose of this study was, therefore, to examine if preadmission antidepressant use in patients with bladder cancer is associated with tumor stage at diagnosis, rate of cystectomy, and surgical outcomes, including survival. METHODS: We performed a registry-based cohort study including all patients with incident invasive bladder cancer in Denmark 2005-2015. Exposure was defined as redemption of two or more antidepressant prescriptions one year before cancer diagnosis. We compared tumor stage using logistic regression, postsurgical inpatient length of stay using linear regression, and other outcomes using Cox regression. All results were adjusted for age, sex, comorbidity, and marital status. RESULTS: Among 10,427 bladder cancer patients, 10% were antidepressant users. At diagnosis, 51% of users and 52% of non-users had muscle-invasive disease. However, upon adjustment for age, sex, comorbidity, and marital status, users had lower odds of muscle-invasive disease (adjusted odds ratio 0.86 (95% confidence interval (CI) 0.74-0.99)). Among patients with muscle-invasive disease, fewer users than non-users had surgery within three months (15% vs. 24%, adjusted hazard ratio (aHR) 0.75 (95% CI 0.59-0.95)). Of 2532 patients undergoing surgery, 6% were antidepressant users. Postsurgical inpatient length of stay did not differ between users and non-users. The 30-day cumulative incidence of readmission was higher for users (41% vs. 33%, aHR 1.33 (95% CI 1.05-1.67)), while the 90-day incidence of postoperative procedures was 44% for users and 38% for non-users (aHR 1.18 (95% CI 0.93-1.51)). One-year mortality was comparable in users (15%) and non-users (14%). CONCLUSIONS: Antidepressant use in bladder cancer patients was associated with less advanced stage at diagnosis and lower rate of cystectomy. After cystectomy, users had higher rate of readmission and postoperative procedures than non-users, but we found no difference in length of stay or one-year mortality. The results point to the importance of differentiated clinical care according to individual patient characteristics

Long-term Health-related Quality of Life Outcomes Following Radical Cystectomy

Objective To evaluate the long-term (>5 years) health-related quality of life (HRQOL) outcomes following radical cystectomy, comparing Indiana pouch (IP), neobladder (NB), and ileal conduit (IC). Materials and Methods The departmental radical cystectomy database was queried to identify patients who underwent radical cystectomy and urinary diversion for bladder cancer between 1991 and 2009 and had not died. Three hundred patients were identified and sent the validated Bladder Cancer Index instrument. Results A total of 128 (43%) patients completed the survey. When adjusted for gender, age at surgery, surgeon, and time since surgery, IC and IP patients had significantly better urinary function than NB patients (P = .0013). Sexual bother was less in NB than IP (P = .0387). Among men ≥65 years of age, IC patients had significantly better urinary function (P = .0376) than NB patients (91.6 vs 49.4, respectively). Among men <65 years of age, IC and IP patients (76.0 and 82.8, respectively) had significantly better urinary function than NB patients (50.7) (P = .0199). Among women greater than 65 years, bowel bother was significantly better (P = .0095) for IC patients than IP patients (44.8 vs 69.5, respectively). Conclusion Urinary diversion type after radical cystectomy affects HRQOL differently in long-term survivors. Age and gender at surgery influenced HRQOL based on diversion procedure. Urinary function but not urinary bother was significantly better in IC and IP compared to NB diversions. Prospective longitudinal studies using validated HRQOL tools will further help guide preoperative diversion choice decisions between patient and surgeon

Risk of Bleomycin-Related Pulmonary Toxicities and Operative Morbidity After Postchemotherapy Retroperitoneal Lymph Node Dissection in Patients With Good-Risk Germ Cell Tumors

Purpose Three cycles of bleomycin, etoposide, and cisplatin (BEP × 3) or four cycles of etoposide and cisplatin (EP × 4) are first-line chemotherapy regimens for men with International Germ Cell Cancer Collaborative Group (IGCCCG) good-risk germ cell tumors (GCTs). We determined whether inclusion of bleomycin affected pulmonary and operative morbidity after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Patients and Methods We queried our database to identify IGCCCG good-risk patients who received BEP × 3 or EP × 4 induction chemotherapy before PC-RPLND from 2006 to 2016. Patients who received combination regimens were excluded. The primary outcomes of interest were pulmonary morbidity (prolonged intubation, reintubation, supplemental oxygen use, intensive care unit stay) and operative morbidity (operative time, length of stay, concomitant procedures, estimated blood loss). Results We analyzed 234 patients (191 BEP × 3 v 43 EP × 4). All patients were extubated immediately after the operation. None were reintubated or discharged on oxygen. Two patients in each cohort required an intensive care unit stay for nonpulmonary reasons. Patients treated with BEP required shorter use of supplemental oxygen (0.99 v 1.63 days; P = .005). No significant differences were found in preoperative mass size (P = .42) or concomitant surgeries (P = .58). Operative time was significantly shorter (131 v 170 minutes; P < .01), and estimated blood loss was considerably less (194 v 226 mL; P < .01) in patients treated with BEP. Length of stay was shorter in patients treated with BEP (3.3 v 3.9 days; P < .01). Conclusion In a modern surgical cohort, the inclusion of bleomycin does not seem to influence pulmonary morbidity, operative difficulty, or nonpulmonary postoperative complications after PC-RPLND in men with IGCCCG good-risk GST

Barriers to Single-Dose Intravesical Chemotherapy in Non-muscle Invasive Bladder Cancer: What's the Problem?

Introduction: The intravesical instillation of mitomycin C immediately following surgery for non-muscle invasive bladder cancer has been shown to be efficacious in reducing cancer recurrence. As a result, the American Urological Association adopted guidelines for non-muscle invasive bladder cancer care to support its use in low to intermediate risk patients. Despite this, urologists' use of this drug following transurethral resection of a bladder tumor (TURBT) has been reported as low as 5% or less. Our study objective was to better understand the barriers urologists experience in using mitomycin C. Methods: Semi-structured interviews were conducted with 13 practicing urologists at 4 geographically distinct practice locations throughout Indiana between 2017 and 2018. Cognitive task analysis was used to explore factors that influenced their clinician decision-making about Mitomycin C use following TURBT in specific patient cases. Interview transcripts were coded and analyzed using immersion/crystallization to identify emergent themes. Results: The median age of the urologists interviewed was 44 (IQR 40-48). Eighty-five percent were male. Approximately 30% had completed urologic fellowship training; 62% were in private practice. Three major themes related to the use of mitomycin C emerged: cumbersome workflow processes, urologists' fears of side effects, and issues of identifying patients most likely to benefit. Conclusion: Workflow, fear, and value are key factors and also represent complexities of translating efficacy into effectiveness for a drug with known benefits to patients. Areas of potential intervention development to improve the use of mitomycin C to reduce recurrence of bladder cancer are suggested. Alternatives such as gemcitabine may also help overcome these barriers

Does Squamous Differentiation Portend Worse Outcomes in Urothelial Bladder Cancer?

Introduction Interest on the impact of variant histology in bladder cancer prognosis is increasing. Although squamous differentiation is the most well characterized, only recently have less common variants gained increased recognition. We assessed whether squamous differentiation conferred a worse prognosis than nonvariant urothelial bladder cancer in a contemporary cohort of patients treated with radical cystectomy given the increased awareness of other less common variants. Methods We identified patients with squamous differentiation or nonvariant histology on transurethral resection of bladder tumor and/or cystectomy pathology during a 10-year period. Disease specific and overall survival were evaluated using Kaplan-Meier methodology. Cox regression was used to assess variables associated with mortality. Results Between 2003 and 2013, 934 patients underwent cystectomy for urothelial bladder cancer. Overall 617 nonvariant and 118 squamous differentiation cases were identified, and the remainder was nonsquamous differentiation variant histology. Overall 75% of patients with squamous differentiation had muscle invasive disease at diagnosis compared with 59% of those with nonvariant histology (p=0.002). Nonorgan confined disease at cystectomy was more common in patients with squamous differentiation (57% vs 44%, p=0.009). Among cases on neoadjuvant chemotherapy 20% (9 of 45) of nonvariant and 13% (1 of 8) of squamous differentiation were pT0N0 (p=0.527). Median followup was 52 months. Adjusted for demographics, pathological stage and chemotherapy, squamous differentiation was not associated with an increased risk of disease specific (HR 1.35, 95% CI 0.90–2.04, p=0.150) or all cause mortality (HR 0.90, 95% CI 0.60–1.25, p=0.515). Conclusions In a contemporary cohort of urothelial bladder cancer with recognition and characterization of less commonly described variants, squamous differentiation is not associated with a worse disease specific and all cause mortality when compared to a pure nonvariant cohort

The changing reality of urothelial bladder cancer: should non-squamous variant histology be managed as a distinct clinical entity?

Objectives To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC). Patients and Methods A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan–Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality. Results Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients. Conclusions While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials

A Prospective Program to Reduce the Clinical Incidence of Clostridium Difficile Colitis Infection after Cystectomy

Purpose The development of Clostridium difficile infection after cystectomy is associated with significant morbidity and mortality. We implemented a prospective screening program to identify asymptomatic carriers of Clostridium difficile and assessed its impact on clinical Clostridium difficile infection rates compared to historical matched controls. Materials and Methods Prospective Clostridium Difficile screening prior to cystectomy began in March 2015. The 380 consecutive patients undergoing cystectomy prior to initiation of screening (control cohort) were matched based on 5 clinical factors with the 386 patients who underwent cystectomy from March 2015 to December 2017 (trial cohort). Screened positive patients were placed in contact isolation and treated prophylactically with Metronidazole. Multivariable models were built on an intention-to-screen and an effectiveness of screening basis to determine if screening reduced the rates of symptomatic Clostridium Difficile infections postoperatively. Results With the implementation of the screening protocol, Clostridium difficile infections rates declined from 9.4 to 5.5% (OR 0.52, p=0.0268) on an intention-to-screen protocol and from 9.2 to 4.9% on an effectiveness of screening protocol (OR 0.46, p=0.0174). Conclusions Clostridium difficile screening prior to cystectomy is associated with a significant decrease in rates of clinically symptomatic infections postoperatively. These results should be confirmed in a randomized controlled trial