Association of Baseline Pre-Diagnosis and Post-Diagnosis Obesity and Weight Change with Cardiovascular Risk and Survival Among Nonmetastatic Prostate Cancer Survivors.

INTRODUCTION: Obesity in prostate cancer survivors may increase mortality. Better characterization of this effect may allow better counseling on obesity as a targetable lifestyle factor to reduce mortality in prostate cancer survivors. The purpose of this study was to determine whether pre- and post-diagnostic obesity and weight change affect all-cause mortality, cardiovascular disease specific mortality, and prostate cancer specific mortality in patients with nonmetastatic prostate cancer. PATIENTS AND METHODS: We performed a retrospective cohort analysis of 5,077 patients diagnosed with localized prostate cancer from 1997 to 2017 with median follow-up of 15.5 years. The Utah Population Database linked to the Utah Cancer Registry was used to identify patients at a variety of treatment centers. RESULTS: Pre-diagnosis obesity was associated with a 62% increased risk of cardiovascular disease specific mortality and a 34% increased risk of all-cause mortality (HR 1.62, 95% CI 1.05-2.50; HR 1.34, 95% CI 1.07-1.67, respectively). Post-diagnosis obesity increased the risk of cardiovascular disease specific mortality (HR 1.83, 95% CI 1.31-2.56) and all-cause mortality (HR 1.37, 95% CI 1.16-1.64) relative to non-obese men. We found no association between pre-diagnostic obesity or post-diagnostic weight gain and prostate cancer specific mortality. CONCLUSION: Our study strengthens the conclusion that pre-, post-diagnostic obesity and weight gain increase cardiovascular disease and all-cause mortality but not prostate cancer specific mortality compared to healthy weight men. An increased emphasis on weight management may improve mortality for prostate cancer survivors who are obese.

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer.

INTRODUCTION: Maximum tumor diameter (MTD) on pretreatment magnetic resonance imaging (MRI) has the potential to further risk stratify for men with prostate cancer (PCa) prior to definitive local therapy. We aim to evaluate the prognostic impact of radiographic maximum tumor diameter (MTD) in men with localized prostate cancer. PATIENTS AND METHODS: From a single-center retrospective cohort of men receiving definitive treatment for PCa (radical prostatectomy [RP] or radiotherapy [RT]) with available pretreatment MRI, we conducted univariable and multivariable Cox proportional-hazards models for progression using clinical variables including age, NCCN risk group, radiographic extracapsular extension (ECE), radiographic seminal vesical invasion (SVI), and MTD. RP and RT cohorts were analyzed separately. Covariates were used in a classification and regression tree (CART) analysis and progression-free survival was estimated with the Kaplan-Meier method and groups were compared using log-rank tests. RESULTS: The cohort included 631 patients (n = 428 RP, n = 203 RT). CART analysis identified 4 prognostic groups for patients treated with RP and 2 prognostic groups in those treated with RT. In the RP cohort, NCCN low/intermediate risk group patients with MTD>=15 mm had significantly worse PFS than those with MTD <= 14 mm, and NCCN high-risk patients with radiographic ECE had significantly worse PFS than those without ECE. In the RT cohort, PFS was significantly worse in the cohort with MTD >= 23 mm than those <= 22 mm. CONCLUSION: Radiographic MTD may be a useful prognostic factor for patients with locoregional prostate cancer. This is the first study to illustrate that the importance of pretreatment tumor size may vary based on treatment modality.

Case of testicular nonseminomatous germ cell tumor cancer soft tissue seeding after inguinal orchiectomy.

A 29-year-old patient presented to his primary care provider complaining of a painful right inguinal swelling. He was referred for inguinal hernia repair, but during surgery, an enlarged necrotic-appearing testicle was observed and removed. Pathology demonstrated a mixed non-seminomatous germ cell tumor (NSGCT) with evidence of tumor violation. After receiving BEPx3 for elevated post-operative AFP his tumor markers normalized. On surveillance, he was found to have several palpable masses around his inguinal incision. On soft tissue excision he was found to have residual teratoma within his soft tissues. We review the literature on germ cell tumor seeding and atypical recurrences.

Clinical Germline Testing Results of Men With Prostate Cancer: Patient-Level Factors and Implications of NCCN Guideline Expansion.

Germline likely pathogenic or pathogenic variants (PVs) have been identified in up to 17% of men with prostate cancer (PC) and may drive disease severity or be targetable by novel therapies. National Comprehensive Cancer Network (NCCN) guidelines encouraging germline testing in metastatic PC were recently expanded to include all men with high-risk, very high-risk, or regional PC. Our aim was to assess the impact of expanded NCCN guidelines on the detection rate of germline PVs and to determine patient-level factors associated with a PV germline testing result. PATIENTS AND METHODS: Men with PC underwent multigene germline genetic testing for PVs from June 2016 to December 2018, and trends were compared. The association of patient-level factors with a PV germline testing result, where ≥ 1 PV was identified, was assessed using analysis of variance and univariate logistic regression. Sensitivity analyses were limited to clinically actionable variants and those associated with disease severity or progression (BRCA1/2 and ATM). RESULTS: Of 408 men undergoing germline testing, 42 (10.3%) men had PVs and 366 (89.7%) men did not have PVs identified. The proportion of men identified with a germline PV remained stable following testing criteria expansion (9.4% v 10.6%, P = .73). No patient-level factors were significantly associated with increased odds of a PV germline testing result, including age at diagnosis, race, pretreatment prostate-specific antigen, Gleason grade group, NCCN risk group, and family history of cancer (breast and/or ovarian, prostate, or any cancer). CONCLUSION: This study demonstrated a stable PV detection rate in men with PC using expanded criteria aligned to the updated NCCN testing guidelines. However, we did not find strong evidence to suggest that patient-level factors are associated with PV germline testing results. These findings support the recent expansion of NCCN germline testing guidelines in PC.

Decision fatigue in low-value prostate cancer screening.

BACKGROUND: Low-value prostate-specific antigen (PSA) testing is common yet contributes substantial waste and downstream patient harm. Decision fatigue may represent an actionable target to reduce low-value urologic care. The objective of this study was to determine whether low-value PSA testing patterns by outpatient clinicians are consistent with decision fatigue. METHODS: Outpatient appointments for adult men without prostate cancer were identified at a large academic health system from 2011 through 2018. The authors assessed the association of appointment time with the likelihood of PSA testing, stratified by patient age and appropriateness of testing based on clinical guidelines. Appointments included those scheduled between 8:00 am and 4:59 pm, with noon omitted. Urologists were examined separately from other clinicians. RESULTS: In 1,581,826 outpatient appointments identified, the median patient age was 54 years (interquartile range, 37-66 years), 1,256,152 participants (79.4%) were White, and 133,693 (8.5%) had family history of prostate cancer. PSA testing would have been appropriate in 36.8% of appointments. Clinicians ordered testing in 3.6% of appropriate appointments and in 1.8% of low-value appointments. Appropriate testing was most likely at 8:00 am (reference group). PSA testing declined through 11:00 am (odds ratio [OR], 0.57; 95% CI, 0.50-0.64) and remained depressed through 4:00 pm (P < .001). Low-value testing was overall less likely (P < .001) and followed a similar trend, declining steadily from 8:00 am (OR, 0.48; 95% CI, 0.42-0.56) through 4:00 pm (P < .001; OR, 0.23; 95% CI, 0.18-0.30). Testing patterns in urologists were noticeably different. CONCLUSIONS: Among most clinicians, outpatient PSA testing behaviors appear to be consistent with decision fatigue. These findings establish decision fatigue as a promising, actionable target for reducing wasteful and low-value practices in routine urologic care. LAY SUMMARY: Decision fatigue causes poorer choices to be made with repetitive decision making. This study used medical records to investigate whether decision fatigue influenced clinicians' likelihood of ordering a low-value screening test (prostate-specific antigen [PSA]) for prostate cancer. In more than 1.5 million outpatient appointments by adult men without prostate cancer, the chances of both appropriate and low-value PSA testing declined as the clinic day progressed, with a larger decline for appropriate testing. Testing patterns in urologists were different from those reported by other clinicians. The authors conclude that outpatient PSA testing behaviors appear to be consistent with decision fatigue among most clinicians, and interventions may reduce wasteful testing and downstream patient harms.

Feasibility of wearable activity trackers in cystectomy patients to monitor for postoperative complications.

BACKGROUND: To determine the feasibility of using wearables in patients undergoing radical cystectomy to monitor postoperative heart rate and activity and attempt to correlate these factors to complications and readmissions. MATERIALS AND METHODS: We conducted a prospective study of 20 patients undergoing radical cystectomy for bladder cancer between June 2017 and March 2018. Each patient was provided with a Garmin Vívofit heart rate (HR) activity tracker and instructed to wear it on their wrist for 30 days postoperatively. Heart rate, steps, and sleep data were collected during this time. Patients were called at 10-day intervals and surveyed for complications and device compliance. Univariable mixed effects logistic regression models were used to compare daily activity tracker measures with occurrence of an adverse event. Odds ratios, 95% confidence intervals, and p-values were reported. RESULTS: Median age was 65 (interquartile range 61-74) years. Patients had usable data for a median of 59.3% (interquartile range 25-71.7%) of the time. Five patients experienced a postoperative event (1 readmission for sepsis from urinary tract source, 1 inpatient rapid response called for tachycardic event, 3 unscheduled visits related to dehydration), where event data was recorded over a total of 17 days. Higher step count was associated with reduced odds of an adverse event (odds ratio 0.31, 95% confidence interval 0.10-0.98 per 1000 steps, p = 0.047). CONCLUSIONS: Postoperative activity and heart rate monitoring in cystectomy patients is feasible though current wearables are not well suited for this task.

18F-fluciclovine PET CT detection of biochemical recurrent prostate cancer at specific PSA thresholds after definitive treatment.

OBJECTIVES: To evaluate various Prostate-Specific Antigen (PSA) thresholds at which a 18F-fluciclovine PET scan could be considered in the setting of biochemical recurrent prostate cancer after definitive treatment. METHODS: We analyzed available records of men who underwent a 18F-fluciclovine PET scan after definitive therapy at a single academic institution between November 2016 to May 2018. The primary outcome was the rate of positive imaging findings at specific PSA thresholds. We then employed empiric strategies including a ROC curve and decision curve analysis to identify a specific threshold for which obtaining a positive result would be optimized. RESULTS: A total of 115 men underwent imaging with 18F-fluciclovine PET. No concerning lesions were identified in 25 (21.7%) patients, 32 (27.8%) had a solitary lesion identified, 45 (39.1%) had 2 to 5 lesions, and 13 (11.3%) had greater than 5 suspicious lesions identified. At PSA thresholds of less than 0.5, 0.5 to 2.0, and greater than 2, lesions were detected in 55.5% (12/22), 70.6% (24/34), and 91.5% (54/59) of patients respectively [P < 0.001]. Our ROC analysis yielded a PSA threshold of 2.10 while our decision curve analysis provided a PSA cutoff of 1.38. CONCLUSION: This study constitutes an early single institution series evaluating the use of 18F-fluciclovine PET scans in the assessment of biochemically recurrent prostate cancer after definitive treatment. The probability of having positive imaging findings and increasing numbers of suspicious lesions rises with increasing PSA. Utilization of a lower PSA threshold of 0.5 may allow earlier intervention with salvage therapies in biochemical recurrence. However, using a threshold below 1 carries a higher risk of negative scans. Employing a higher PSA threshold of 1 to 2 carries greater sensitivity and specificity and may maximize identifying individuals with early BCR who may benefit from early intervention, while minimizing negative scans.

Metastasis, Mortality, and Quality of Life for Men With NCCN High and Very High Risk Localized Prostate Cancer After Surgical and/or Combined Modality Radiotherapy.

PURPOSE: To compare metastasis-free survival, overall survival, and patient-reported quality of life (QOL) of men with National Comprehensive Cancer Network high or very high risk prostate cancer after definitive surgery and/or multimodal radiotherapy (RT). PATIENTS AND METHODS: We studied a retrospective cohort study of 586 patients treated between the years 2000 and 2017 receiving radical prostatectomy with or without postoperative RT, external-beam RT (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy (Brachy) boost + ADT. Patient-reported QOL for urinary, bowel, sexual, and overall physical and mental functioning was assessed using the American Urological Association symptom scale, the Sexual Health Inventory in Men, the Rectal-Function Assessment Scale, the Expanded Prostate Cancer Index Composite, and the Veterans RAND 12-Item Health Survey. RESULTS: Median follow-up for survival was 5 years. No significant differences between the treatments were observed for overall survival or metastasis-free survival at the P < .05 threshold. The propensity-adjusted 5-year metastasis-free survival estimates for EBRT + ADT, EBRT + Brachy + ADT, and surgery were 74.6%, 94.8%, and 83.1%, respectively. The EBRT + Brachy + ADT and surgery cohorts had significantly worse mean American Urological Association symptom scores at 6 months than the EBRT + ADT cohort, which resolved by 1 year. Surgical patients had better rectal function scores than EBRT + ADT patients at years 1 to 3, but similar function thereafter. Adjuvant or salvage RT resulted in significant declines in various Expanded Prostate Cancer Index Composite urinary, sexual, and bowel domains, and Veterans RAND 12-Item Health Survey physical but not mental domains. CONCLUSION: Men with very and/or high-risk localized prostate cancer are likely to require multimodal therapy. The overall differences in survival and long-term QOL are similar for men choosing surgical versus RT pathways.

Harnessing Population Pedigree Data and Machine Learning Methods to Identify Patterns of Familial Bladder Cancer Risk.

BACKGROUND: Relatives of patients with bladder cancer have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking-related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multicancer configurations (multiple different cancer types that cluster in relatives) surrounding patients with familial bladder cancer. METHODS: This study takes advantage of a unique population-level data resource, the Utah Population Database (UPDB), containing vast genealogy and statewide cancer data. Familial risk is measured using standardized incidence risk (SIR) ratios that account for sex, age, birth cohort, and person-years of the pedigree members. RESULTS: We identify 1,023 families with a significantly higher bladder cancer rate than population controls (familial bladder cancer). Familial SIRs are then calculated across 25 cancer types, and a weighted Gower distance with K-medoids clustering is used to identify familial multicancer configurations (FMC). We found five FMCs, each exhibiting a different pattern of cancer aggregation. Of the 25 cancer types studied, kidney and prostate cancers were most commonly enriched in the familial bladder cancer clusters. Laryngeal, lung, stomach, acute lymphocytic leukemia, Hodgkin disease, soft-tissue carcinoma, esophageal, breast, lung, uterine, thyroid, and melanoma cancers were the other cancer types with increased incidence in familial bladder cancer families. CONCLUSIONS: This study identified five familial bladder cancer FMCs showing unique risk patterns for cancers of other organs, suggesting phenotypic heterogeneity familial bladder cancer. IMPACT: FMC configurations could permit better definitions of cancer phenotypes (subtypes or multicancer) for gene discovery and environmental risk factor studies.

Elderly patients undergoing cystectomy, comparing preoperative American Society of Anesthesiology and Eastern Cooperative Oncology Group scores and operative approaches.

OBJECTIVE: To evaluate preoperative scoring systems and operative management and their relation to complications in patients older than 75 years undergoing cystectomy at two academic institutions. METHODS: In total, 212 patients aged 75-95 years with muscle invasive bladder cancer underwent cystectomy at the University of Utah and Central Hospital of Bolzano, Italy. The rates of Grade 3 Clavien-Dindo complications and above in radical cystectomy patients (n = 199) were compared using Eastern Cooperative Oncology Group Scores and American Society of Anesthesiologists Physical Status Classification. The rates of Grade 3 Clavien-Dindo complications and above were also compared by urinary diversion type. Logistic regression was used to control for source institution. RESULTS: In total, 199 cases were included in the primary analysis. Neither of the preoperative scoring systems were predictive for identification of radical cystectomy patients with ⩾Grade 3 Clavien-Dindo complications. In secondary analysis (n = 212, including partial cystectomy), none of the urinary diversion types associated with radical cystectomy had a significantly different rate of complications. However, partial cystectomy (n = 13) had a significantly lower rate of complications. CONCLUSION: Complication rates among elderly patients undergoing cystectomy for muscle invasive bladder cancer were very high. For patients who are approved for surgery after the history and physical exam, none of our objective metrics adequately predicted operative risk. A unique diversion procedure described by the Bolzano group, uretero-ureterocutaneostomy, had equivalent complication rates to the more common diversion procedures. It also appears based on outcomes in this cohort that partial cystectomy is a particularly favorable option within the elderly population in terms of perioperative morbidity.

Describing the Spectrum of Patient Reported Outcomes after Radical Prostatectomy: Providing Information to Improve Patient Counseling and Shared Decision Making.

PURPOSE: Preoperative counseling incorporating the best case, the worst case and the most likely outcome scenarios aid patient decision making. This information is not readily available for prostate cancer counseling because most patient reported outcomes are presented as averages, which minimize individual patient experiences. Using the EPIC (Expanded Prostate Index Composite) we present data to characterize the best case and the worst case after prostatectomy. MATERIALS AND METHODS: The EPIC bowel, urinary irritation, continence and sexual function scores were measured in 1,418 men stratified by baseline function who underwent prostatectomy. Patient level functional trajectories were modeled using a Bayesian hierarchical model. The 5-year best and worst case outcomes were defined as the upper 95th and the lower 5th percentiles, respectively. RESULTS: Five years after surgery in patients with good baseline urinary continence the best case was a score of 100.0 (95% credible interval 100.0-100.0) and the worst case was 54.4 (95% credible interval 42.2-63.7). Among men with good baseline sexual function who underwent nerve sparing surgery the best case was 83.9 points (95% credible interval 74.1-93.1) and the worst case was 17.6 (95% credible interval 7.5-26.1). The differences between best and worst case for bowel and urinary irritation were relatively small (11.4 and 13.6 points, respectively). CONCLUSIONS: Prostatectomy exerted a minimal negative impact on urinary irritation and bowel function with minimal variability. There was a larger range in patient experience for urinary continence and sexual function with most patients experiencing a significant functional decline. Future studies of best and worst case outcomes of multiple treatment modalities may provide valuable information for shared decision making in prostate cancer treatment.

Modulation of Premetastatic Niche by the Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Pazopanib in Localized High-Risk Prostate Cancer Followed by Radical Prostatectomy: A Phase II Randomized Trial.

LESSONS LEARNED: Pazopanib was not effective in altering the premetastatic niche in the neoadjuvant setting.Pazopanib was safe and well tolerated without any new safety signals. BACKGROUND: Vascular endothelial growth factor receptor 1 (VEGFR1) expressing myeloid-derived suppressor cells (VEGFR1+ MDSCs) potentially foster metastases by establishing a premetastatic niche. In a preclinical study, VEGFR1+ clustering in lymph nodes (LNs) independently predicted time to biochemical recurrence (TTBR) in localized prostate cancer [1]. The hypothesis was that neoadjuvant pazopanib therapy will decrease VEGFR1+ clusters in pelvic lymph nodes and improve outcomes. METHODS: This is a phase II trial (NCT01832259) of neoadjuvant pazopanib 800 mg versus placebo daily for 4 weeks in high-risk localized prostate cancer. The primary endpoint was a decrease in VEGFR1+ MDSC clustering assessed by immunohistochemistry (IHC) analysis. Secondary endpoints were safety, feasibility, and TTBR. RESULTS: Thirty patients were randomized to pazopanib versus placebo, with 15 patients randomized to each arm. Demographic and disease characteristics were similar in both arms. There was no difference in the VEGFR1+ clustering between the treatment arms (p = .345). Neoadjuvant therapy with pazopanib was well tolerated, and surgical complications were similar in both arms. CONCLUSION: Neoadjuvant pazopanib therapy did not alter the premetastatic niche; however, treatment targeting vascular endothelial growth factor (VEGF) in the preoperative period was safe and feasible, which may open up the avenue to investigate novel combinatorial regimens, including a VEGF inhibitor in combination with immune checkpoint inhibitor in this setting.

Orgasmic Function after Radical Prostatectomy.

PURPOSE: We examined postprostatectomy orgasmic function and assessed for potential predictors. MATERIALS AND METHODS: Between 2005 and 2013, 499 men underwent radical prostatectomy and completed quality of life questionnaires prospectively before surgery and at regular postoperative intervals. We used mixed effects logistic regression models to evaluate average differences in followup measures and interactions with time. RESULTS: At a median followup of 36 months orgasmic function was worse, stable or improved in 300 (60.1%), 152 (30.5%) and 47 men (9.4%), respectively. Orgasmic function recovery plateaued at 15 to 21 months. High postoperative orgasmic function was positively associated with younger age (50 years or younger vs 51 to 60 OR 3.40, 95% CI 1.56-7.41), nerve sparing (bilateral OR 7.11, 95% CI 2.55-19.77, modified 4.34, 95% CI 1.38-13.58 and unilateral OR 3.93, 95% CI 1.17-13.16), erectile function (OR 4.67, 95% CI 3.32-6.57) and sexual desire (OR 5.51, 95% CI 3.95-7.68) but negatively associated with lower urinary tract symptoms (OR 0.58, 95% CI 0.41-0.82) and urinary incontinence (OR 0.38, 95% CI 0.25-0.56). Although robotic status did not influence orgasmic function in the overall cohort, it was associated with faster recovery on subgroup analysis of 356 patients with long followup. On another subgroup analysis of 235 men with long followup and poor erectile function the association of high preoperative orgasmic function and bilateral nerve sparing with high orgasmic function persisted, suggesting an independent effect on orgasmic function apart from that on erectile function. CONCLUSIONS: Orgasmic function recovery after radical prostatectomy is a lengthy process. Predictors of orgasmic function include preoperative orgasmic function, age, nerve sparing status, erectile function, sexual desire and urinary control and function.

Quality of Life Following Prostatectomy as a Function of Surgery Type and Degree of Nerve Sparing.

OBJECTIVES: To compare robotic-assisted laparoscopic prostatectomy with conventional retropubic radical prostatectomy in maintaining pre-surgery levels of urinary and sexual functioning and to evaluate the efficacy of nerve sparing in prostatectomies in protecting urinary functioning. MATERIAL AND METHODS: Patients (n = 385) receiving both surgical procedures were surveyed prior to surgery. Multiple measures, including the Expanded Prostate Cancer Index Composite, the Sexual Health Inventory for Men, and the International Prostate Symptom Score, assessed sexual and urinary function at an average of 12 months post-surgery. RESULTS: Across multiple measures, while controlling for pre-surgical sexual functioning, robotic-assisted surgery did not offer an advantage in maintaining sexual or urinary function an average of a year following the prostatectomy. Bilateral nerve sparing offered a strong and reliable advantage in the maintenance of sexual function, but not so regarding urinary function. CONCLUSION: While robotic-assisted prostatectomies may offer a number of medical advantages over open procedures, we found no significant effect on important quality of life outcomes associated with the technique.

Durable Response to Treatment With Combination Radiotherapy and High-dose Interleukin-2 in Metastatic Chromophobe Variant Renal Cell Carcinoma.

This is a report of chromophobe renal cell carcinoma (ChRCC), a rare entity that accounts for 6% to 11% of cases of renal cell carcinoma (RCC). ChRCC is considered to yield a good prognosis as it typically presents as an early stage tumor with longer overall survival when compared with clear cell RCC; however, metastatic disease negates this survival difference and is characterized by poor prognosis. The available clinical investigations supporting the guidelines for treatment of metastatic RCC are predominantly based on clear cell RCC studies. There are no data supporting the applicability of guidelines used to treat clear cell to the management of patients with the ChRCC. This case report describes a male patient who initially presented with locally advanced chromophobe variant RCC, pathologically staged T3aN1M0, initially treated with radical nephrectomy. After developing pathologically confirmed metastatic disease, the patient was treated with repeated cycles of combined hypofractionated radiotherapy to symptomatic metastatic disease sites followed by high-dose intravenous interleukin-2 (HD IL-2) subsequently achieving a near complete and durable response. Three months after initiation of HD IL-2 and radiotherapy, the patient achieved a partial response, and after 6 months he achieved a near complete response. At the time of most recent follow-up, over 36 months after the diagnosis of metastatic disease, the patient remained in remission. On the basis of this experience, we hypothesize that immunomodulation from the radiation potentiated an immune response to HD IL-2 leading to near complete and a durable response in this patient with metastatic ChRCC.

Prognostic impact of infiltration of the vagina and/or uterus in women undergoing anterior pelvic exenteration for urothelial carcinoma of the bladder: results of a contemporary multicentre series.

PURPOSE: To evaluate for the first time the prognostic significance of female invasive patterns in stage pT4a urothelial carcinoma of the bladder in a large series of women undergoing anterior pelvic exenteration. PATIENTS AND METHODS: Our series comprised of 92 female patients in total of whom 87 with known invasion patterns were eligible for final analysis. Median follow-up for evaluation of cancer-specific mortality (CSM) was 38 months (interquartile ranges, 21-82 months). The impact on CSM was evaluated using multivariable Cox proportional-hazards regression analysis; predictive accuracy (PA) was assessed by receiver operating characteristic analysis. RESULTS: Vaginal invasion was noted in 33 patients (37.9 %; group VAG), uterine invasion in 20 patients (23 %; group UT), and infiltration of both vagina and uterus in 34 patients (39.1 %; group VAG + UT). Groups VAG and UT significantly differed from group VAG + UT with regard to the presence of positive soft tissue margins (STM) only. Five-year-cancer-specific survival probabilities in the groups VAG, UT, and VAG + UT were 21, 20, and 21 %, respectively (p = 0.955). On multivariable analysis, only STM status (HR = 2.02, p = 0.023) independently influenced CSM. C-indices of multivariable models for CSM with and without integration of invasive patterns were 0.570 and 0.567, respectively (PA gain 0.3 %, p = 0.526). CONCLUSIONS: Infiltration of the vagina, the uterus or both is associated with poor 5-year survival rates. With regard to CSM, no difference was detectable between patients with different invasion patterns, thus justifying further collectively including these invasive patterns as stage pT4a.

Comparison of complications from radical cystectomy between old-old versus oldest-old patients.

INTRODUCTION: The purpose of this study was to evaluate and compare complications after radical cystectomy in patients aged ≥75 years. MATERIALS AND METHODS: 251 patients aged 75-95 years (median 79) underwent radical cystectomy between 2000 and 2012 at four institutions. The patients were divided into two groups: ≥75-84 years of age (group 1) versus ≥85 years of age (group 2). Comorbidities, body mass index, and complications were obtained retrospectively, except at the Central Hospital of Bolzano and Weill Cornell Medical Center, which collected data prospectively. Cancer-specific survival, overall mortality, hospital stay, clinical outcome and complications were assessed. Complications were categorized using the Clavien-Dindo classification reporting system. The mean follow-up was 21 months. RESULTS: The median hospital stay was 17 (2-91) days. Perioperative Clavien-Dindo grade ≥III complications were seen in 24.1% (48/199) of group 1 patients and 19.2% (10/52) of group 2 patients (p = 0.045). 30- and 90-day mortality was 4.5 and 13.5% in group 1 and 6.5 and 32.3% in group 2, respectively. Only the 90-day mortality rate was statistically significant (p < 0.05) between the two groups. The 3-year overall survival was 40% in group 1 and 34% in group 2. The 3-year cancer-specific survival was 52% in group 1 and 50% in group 2. CONCLUSIONS: We evaluated a large series of elderly (≥75 years) patients undergoing radical cystectomy at four institutions. Comparing patients aged ≥75-84 and ≥85 years revealed no significant difference in complications, 30-day mortality, overall and cancer-specific survival rates. Only 90-day mortality rates were significantly higher in the ≥85-year-old patients.

Preoperative C-reactive protein in the serum: a prognostic biomarker for upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

OBJECTIVE: To investigate the impact of preoperative serum C-reactive protein (CRP) on clinicopathological features and prognosis in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU). PATIENTS AND METHODS: Data of 265 patients from three German centers who underwent RNU for UTUC without neoadjuvant chemotherapy between 1990 and 2012 were evaluated. Mean follow-up was 37 months (interquartile range 9-48). CRP was analyzed as a categorical and continuous variable for the prediction of recurrence-free survival (RFS), disease-specific survival (DSS) and all-cause survival (ACS) using uni- and multivariate Cox regression analyses. RESULTS: The optimal cutoff for CRP was calculated by the Youden index at 0.90 mg/dl. Elevated CRP was significantly associated with pT3/4 and pN+ in a preoperative model including age, gender, tumor multifocality, tumor localization and the Eastern Cooperative Oncology Group Performance Status. In a multivariable Cox regression model adjusted for features significant in univariable analysis, categorized and continuous CRP levels were both independent predictors for RFS [hazard ratio (HR) 1.18, p = 0.050; HR 1.03, p = 0.012] and DSS (HR 1.61, p = 0.026; HR 1.06, p = 0.001). Continuous CRP was an independent predictor for ACS (HR 1.05, p = 0.036). CONCLUSIONS: Elevated preoperative CRP is significantly associated with aggressive tumor biology and an independent predictor for poor survival after RNU. Preoperative serum CRP represents an easily obtainable and cost-effective marker in UTUC and may help in counseling patients with regard to operative management and/or adjuvant or neoadjuvant therapies.

The Charlson comorbidity index predicts survival after disease recurrence in patients following radical cystectomy for urothelial carcinoma of the bladder.

OBJECTIVE: To identify prognostic clinical and histopathological parameters, including comorbidity indices at the time of radical cystectomy (RC), for overall survival (OS) after recurrence following RC for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: A retrospective multicenter study was carried out in 555 unselected consecutive patients who underwent RC with pelvic lymph node dissection for UCB from 2000 to 2010. A total of 227 patients with recurrence comprised our study group. Cox proportional hazards regression models were calculated with established variables to assess their independent influence on OS after recurrence. RESULTS: The median time from RC to recurrence and the median OS after recurrence was 10.9 and 5.4 months, respectively. Neither the time to recurrence nor the type of recurrence (systematic vs. local) was predictive of the OS. In contrast, age (hazard ratio (HR) 1.53, p = 0.011), lymph node metastasis (HR 1.56, p = 0.007), and positive surgical margins (HR 1.53, p = 0.046) significantly affected the OS after disease recurrence. In addition, the dichotomized Charlson comorbidity index (CCI; dichotomized into >2 vs. 0-2) was the only comorbidity score with an independent prediction of OS (HR 1.41, p = 0.033). We observed a significant gain in the base model's predictive accuracy, i.e. from 68.4 to 70.3% (p < 0.001), after inclusion of the dichotomized CCI. CONCLUSIONS: We present the first outcome study of comorbidity indices used as predictors of OS after disease recurrence in patients undergoing RC for UCB. The CCI at the time of RC had no significant influence on the time to recurrence but represented an independent predictor of OS after disease recurrence.

Use of a polytetrafluoroethylene (GORE-TEX) bolster to close the renal parenchymal defect during open partial nephrectomy.

INTRODUCTION: Numerous surgical techniques have been described to facilitate closure of the renal parenchymal defect. We sought to describe the operative technique and define the safety and efficacy of using an expanded polytetrafluoroethylene (GORE-TEX; WL Gore and Associates, Flagstaff, AZ) bolster to aid in closure of the renal parenchymal defect at the time of open partial nephrectomy (OPN). TECHNICAL CONSIDERATIONS: A retrospective review of 175 patients who underwent an OPN using an expanded polytetrafluoroethylene (ePTFE) bolster at the Huntsman Cancer Hospital, University of Utah and Salt Lake City Veterans Affairs Medical Center from March 2005 to February 2013 was conducted. Postoperative complications occurring within 90 days were graded using the Clavien grading system. CONCLUSION: Overall, 57 patients (32.6%) experienced a postoperative complication. Fifteen patients (8.5%) had a Clavien ≥ grade-III complication. Ten patients (5.7%) received blood transfusions. Urine leak requiring intervention occurred in 2 patients (1.1%). Delayed hemorrhage requiring nephrectomy and pseudoaneurysm formation were rare, occurring in 1 patient each (0.6%). Infection of the ePTFE material occurred in 2 patients (1.1%). In both cases, it was explanted without requiring nephrectomy. The use of an ePTFE bolster is an effective and safe method of closing the renal parenchymal defect after OPN with an acceptable 90-day postoperative complication rate and a low risk of infection.