Clinicopathologic and survival correlates of embryonal rhabdomyosarcoma driven by RAS/RAF mutations.

Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of rhabdomyosarcoma (RMS). Among RMS subtypes, ERMS is associated with a favorable outcome with an overall survival of 70% at 5 years for localized disease. The molecular profile of ERMS is heterogeneous, including mostly point mutations in various genes. Therapeutic strategies have remained relatively consistent irrespective of the molecular abnormalities. In this study, we focus on a homogeneous RAS/RAF mutated ERMS subset and correlate with clinicopathologic findings. Twenty-six cases (16 males and 10 females) were identified from screening 98 ERMS, either by targeted DNA sequencing (MSK-IMPACT) or by Sanger sequencing. Fourteen (54%) cases had NRAS mutations, 6 (23%) had KRAS mutations, 5 (19%) had HRAS mutations, and 1 case (4%) had BRAF mutation. Median age at diagnosis was 8 years (range 1-70) with two-thirds occurring in the children. Tumor sites varied with H&N and GU sites accounting for 62% of cases. RAS isoform hot spot mutations predominated: NRAS p.Q61K (57%), KRAS p.G12D (67%), and HRAS (codons 12, 14, and 61). Additional genetic abnormalities were identified in 85% of the RAS-mutated cases. At last follow-up, 29% of patients died of disease and 23% were alive with disease. The 3-year and 5-year survival rates were 75% and 61% respectively. In conclusion, RAS mutations occur in 27% of ERMS, with NRAS mutations encompassing half of the cases. Overall RAS-mutant RMS does not correlate with age or site, but most tumors show an undifferentiated and spindle cell morphology.

Subsequent primary urogenital cancers among childhood and adolescent cancer survivors in the United States.

PURPOSE: To conduct an updated and comprehensive study on the risks of subsequent primary urogenital cancers for childhood and adolescent cancer survivors. METHODS: This longitudinal study was conducted using 9 cancer registries from the Surveillance, Epidemiology and End Results (SEER) Program with follow-up from 1975 to 2017. There were 43,991 patients diagnosed with first primary cancer from 1975 to 2016 before the age of 20 years who subsequently survived for at least 1 year. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) for urogenital cancers were calculated. RESULTS: Compared with the general population, the risk of urinary system cancer was significantly higher in both female (SIR = 5.18, 95% CI: 3.65-7.14) and male (SIR = 2.80, 95% CI: 1.94-3.92) survivors of any first cancer, with shorter median interval length between first cancer and subsequent urinary system cancer for male survivors (19.9 years) than female survivors (29.3 years). Females also had significantly higher SIR than males for subsequent urinary system cancer (SIRfemale:male=1.86, 95% CI: 1.13-3.03) and kidney cancer (SIRfemale:male = 1.97, 95% CI: 1.11-3.53). Compared with the general population, females with any first cancer had significantly higher risks for cancers of the corpus uteri (SIR = 2.32, 95% CI: 1.49-3.45) and vulva (SIR = 4.27, 95% CI: 1.38-9.95). CONCLUSIONS: Childhood and adolescent cancer survivors may have greater female susceptibility for developing subsequent urinary system and kidney cancers, and these survivors may have higher risks for specific types of reproductive system cancers. Our findings may lead to better awareness and surveillance for urogenital cancer by these cancer survivors and their physicians.

Prognostic significance of programmed cell death-ligand 1 expression on circulating tumor cells in various cancers: A systematic review and meta-analysis.

BACKGROUND: The prognostic significance of programmed cell death-ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) has been explored but is still in controversy. We performed, for the first time, a meta-analysis to systematically evaluate its prognostic value in human cancers. METHODS: Literature databases were searched for eligible studies prior to June 30, 2021. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the associations of pre-treatment and post-treatment PD-L1+ CTCs with progression-free survival (PFS) and overall survival (OS). Subgroup analyses with regards to cancer type, treatment, CTC enrichment method, PD-L1 detection method, cut-off, and specifically the comparison model were performed. RESULTS: We included 30 eligible studies (32 cohorts, 1419 cancer patients) in our analysis. Pre-treatment PD-L1+ CTCs detected by immunofluorescence (IF) tended to predict better PFS (HR = 0.55, 95% CI 0.28-1.08, p = 0.084) and OS (HR = 0.61, 95% CI 0.36-1.04, p = 0.067) for immune checkpoint inhibitor (ICI) treatment, but were significantly associated with unfavorable survival for non-ICI therapies (PFS: HR = 1.85, 95% CI 1.21-2.85, p = 0.005; OS: HR = 2.44, 95% CI 1.69-3.51, p < 0.001). Post-treatment PD-L1+ CTCs predicted markedly worse PFS and OS. The prognostic value was obviously modulated by comparison models. Among patients with detectable CTCs, PD-L1+ individuals had comparable survival to PD-L1- individuals, except ICI treatment for which PD-L1+ may predict better PFS (HR = 0.42, 95% CI 0.17-1.06, p = 0.067). Patients with PD-L1+ CTCs had worse survival prognosis compared to those without PD-L1+ CTCs in overall analysis (PFS: HR = 2.10, 95% CI 1.59-2.77, p < 0.001; OS: HR = 2.55, 95% CI 1.70-3.81, p < 0.001) and in most subgroups. CONCLUSIONS: Our analysis demonstrated that PD-L1 positive expression on CTCs predicted better survival prognosis for ICI treatment but worse survival for other therapies, which thus can be potentially used as a prognostic marker of malignant tumor treatment. However, the prognostic value of PD-L1+ CTCs for ICI treatment needs validation by more large-scale studies in the future.

Impact of self-decision to stop cancer treatment on advanced genitourinary cancer patients.

ABSTRACT: Decision-making to stop cancer treatment in patients with advanced cancer is stressful, and it significantly influences subsequent end-of-life palliative treatment. However, little is known about the extent to which the patient's self-decisions influenced the prognostic period. This study focused on the patient's self-decision and investigated the impact of the self-decision to stop cancer treatment on their post-cancer treatment survival period and place of death.We retrospectively analyzed 167 cases of advanced genitourinary cancer patients (kidney cancer: 42; bladder cancer: 68; prostate cancer: 57) treated at the University of Fukui Hospital (UFH), who later died because of cancer. Of these, 100 patients decided to stop cancer treatment by themselves (self-decision group), while the families of the remaining 67 patients (family's decision group) decided to stop treatment on their behalf because the patient's decision-making ability was already impaired. Differences in the post-cancer-treatment survival period and place of death between the 2 groups were examined. The association between place of death and survival period was also analyzed.The median survival period after terminating cancer treatment was approximately 6 times longer in the self-decision group (145.5 days in self-decision group vs 23.0 days in family's decision group, P < .001). Proportions for places of death were as follows: among the self-decision group, 42.0% of patients died at UFH, 45.0% at other medical institutions, and 13.0% at home; among the family's decision group, 62.7% died at UFH, 32.8% at other medical institutions, and 4.5% at home. The proportion of patients who died at UFH was significantly higher among the family's decision group (P = .011). The median survival period was significantly shorter for patients who died at UFH (UFH: 30.0 days; other institutions/home: 161.0 days; P < .001).Significantly longer post-cancer-treatment survival period and higher home death rate were observed among patients whose cancer treatment was terminated based on their self-decision. Our results provide clinical evidence, especially in terms of prognostic period and place of death that support the importance of discussing bad news, such as stopping cancer treatment with patients.

Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies.

BACKGROUND: In this multicenter, single-arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616). METHODS: Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1). RESULTS: Fifty-five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow-up was 9.9 months (range, 1 to 21 months). Twenty-eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1-18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%-25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty-two patients (40%) developed treatment-related grade 3 or higher toxicities; 24% (n = 13) required high-dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related. CONCLUSIONS: Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing. LAY SUMMARY: Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination.

Hot or Not: Tumor Mutational Burden (TMB) as a Biomarker of Immunotherapy Response in Genitourinary Cancers.

Pembrolizumab was recently approved for treatment of cancers with high tumor mutational burden (TMB). We conduct a focused literature review of TMB as a predictive biomarker. TMB quantifies the sum of nonsynonymous coding mutations (typically single nucleotide substitutions and short insertion-deletions) per megabase of sequenced DNA. As a proxy for expression of immunogenic neoantigens, TMB may be an effective predictive biomarker for response to immune checkpoint inhibitors. However, like other biomarkers in this setting, TMB has many limitations; the effect of this FDA approval in the current management of genitourinary cancers is likely limited to select situations.

Clear Cell Adenocarcinoma in Men: A Series of 15 Cases.

Clear cell adenocarcinoma (CCA) is a rare tumor in the genitourinary tract with female predominance and few reports in men. We identified 15 cases of CCA in men evaluated at our institution. Five arose in the bladder, 7 in the prostate or prostatic urethra, 2 in the membranous urethra (1 multifocal in the prostatic and membranous urethra), 1 periprostatic (likely from an embryologic remnant), and 1 between rectum and bladder (likely in a prostatic utricle cyst). No cases showed associated Müllerian structures. One case showed separate foci of nephrogenic adenoma at diagnosis, and 1 case showed urothelial carcinoma in situ on a later follow-up biopsy. Four tumors extended into other organs (prostate to seminal vesicle and periprostatic soft tissue, periprostatic soft tissue to prostate, prostatic urethra to bladder and rectum, and prostate to bladder neck). One tumor showed extraprostatic extension alone. Four tumors metastasized to lymph nodes, with 3 also metastasizing to other sites (bladder, lung and adrenal, and right flank). Eleven patients underwent resection, including 3 transurethral resections. Seven underwent other treatments, including radiation (5 [1 for recurrence]), chemotherapy (3), hormonal therapy (3), immunotherapy with nivolumab (1), and targeted therapy with gefitinib (1). The mean follow-up was 35 months (range: 1 to 138 mo). At the last follow-up, 7 patients showed no evident disease and 3 were alive with disease. Four died with the cause of death unknown, with 2 cases having confirmed disease at the time of death and the remaining 2 dying less than a year after diagnosis. The mean time to death was 16 months (range: 6 to 39 mo). No follow-up was available on 1 patient. All patients who died in this series had CCA of the prostate or prostatic urethra. Pathologists need to be attuned to CCA occurring in males, given that the literature emphasizes its occurrence in females. In addition to established sites such as bladder and urethra, our series demonstrates that tumor may present in unusual adjacent sites, such as in periprostatic embryologic remnants or prostatic utricle.

Biotech and Breakthroughs in Immuno-Oncology.

The age of immuno-oncology has ushered in a rush within the biopharmaceutical industry. This intense focus has been characterized as a frenzy or overhyped, but represents a substantial investment in new products that hope to harness the immune system against cancer. Such agents include next-generation checkpoint antagonists, immune costimulatory agonists, and a diverse array of novel mechanisms of action and therapeutic modalities targeting immune cell types and the interplay of the host and tumor at the immune synapse. This article surveys the clinical development and investment activity with Immuno-Oncology, specifically prostate, kidney, and bladder cancers.

A competing risk analysis of death patterns in male genitourinary cancer.

BACKGROUND: Early diagnosis and improved therapeutic options have contributed to prolonged survival in male genitourinary cancer. However, these cancer survivors may die due to other causes. AIMS: This work is aimed to explore the death patterns among male genitourinary cancer patients due to other causes. The occurrence of death not related to cancer is defined as competing risk (CR). METHODS AND RESULTS: Data extracted between 1973 and 2014 for male patients (n = 638 393) diagnosed with genitourinary cancer and registered in the Surveillance, Epidemiology, and End Results (SEER) Program were included for analysis. A CR analysis was performed to explore the death patterns due to cancer or otherwise. Our study evidenced a huge proportion of patients' death due to associated factors including but not limited to cancer. Interestingly, the computed hazard ratios obtained in cancers of male organ sites such as prepuce, glans penis, penis, and spermatic cord were 1.28 (0.98-1.67), 1.53 (1.33-1.77), 1.35 (0.19-1.53), and 1.57 (1.24-2.0), respectively. However, the hazard ratios evaluated on factors other than cancer in the same organ sites were 0.95 (0.76-1.18), 1.14 (0.99-1.3), 1.09 (0.97-1.22), and 1.12 (0.86-1.46), respectively. CONCLUSION: This study shows that among the male genitourinary cancer patients, the significant proportion of deaths occurs due to reasons unrelated to cancer. It can be concluded that the magnitude of death due to only genitourinary cancer is minimal and is not as high as documented in the earlier literature.

Ano-uro-genital mucosal melanoma UK national guidelines.

Ano-uro-genital (AUG) mucosal melanomas are rare cancers associated with poor outcomes and limited evidence-based management. The United Kingdom AUG mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations regarding the diagnosis, treatment and surveillance of patients diagnosed with AUG mucosal melanomas. The guidelines were sent for international peer review, and are accredited by The National Institute for Health and Clinical Excellence (NICE). A summary of the key recommendations is presented. The full documents are available on the Melanoma Focus website.

Emergency room imaging in patients with genitourinary cancers: analysis of the spectrum of CT findings and their relation to patient outcomes.

PURPOSE: To assess the spectrum of computed tomography (CT) findings in patients with genitourinary cancers visiting the emergency room (ER) and evaluate the relationship between CT findings and overall survival (OS). METHODS: Retrospective analysis of consecutive patients with genitourinary cancers undergoing CT during an ER visit at a tertiary cancer center during a 20-month period. CTs were considered positive if there were findings relevant to the presenting complaint(s). Demographic/clinical variables were recorded. OS was evaluated using Kaplan-Meier curves. Univariate and multivariate Cox proportional hazards regression (HR) was used to evaluate OS predictors. RESULTS: Two hundred twenty-seven patients (243 visits) were included. The most common primary tumors were prostate (121 [49.8%]), bladder/urothelial (78 [32.1%]), and renal (69 [28.4%]). Common presenting complaints were abdominal pain (67 [27.6%]), respiratory symptoms (49 [20.2%]), neurological signs (37 [15.2%]), and fever (34 [14.0%]). CT findings were positive in 172 patients (70.8%) and included new/increased metastases (21.4% [52/243]), fluid collections (7.4% [18/243]), urinary tract infection/inflammation (6.2% [15/243]), enteritis/colitis (5.3% [13/243]), and pneumonia (4.9% [12/243]). A positive ER CT was associated with patient admission (p = 0.01). At multivariate analysis, independently predictive factors of shorter survival were positive ER CT (HR = 2.09 [95% CI 1.16-3.76, p = 0.01), hospital admission (HR = 2.17 [95% CI 1.38-3.41], p < 0.01), and recent systemic treatment (HR = 2.10 [95% CI 1.32-3.35], p < 0.01). CONCLUSION: When CT was performed, it was able to identify a structural cause for the presenting complaint in the majority of patients with genitourinary cancers attending the ER. A positive ER CT was associated with hospital admission and poorer overall survival.

All-cancer incidence in Tehranian adults: more than a decade of follow-up-results from the Tehran Lipid and Glucose Study.

OBJECTIVES: To investigate the incidence rates for different malignancies and assess the risk factors for all-cancer incidence in Tehran. STUDY DESIGN: Cohort study. METHODS: This study consists of 8599 participants aged ≥ 30 years who were free of cancer (3935 men). Cancer diagnosis was based on pathology reports. Sex-stratified crude incidence rates and age-standardized incidence rates (ASRs) using Segi's method were calculated for all-cancers. Multivariate Poisson regression models were used to evaluate associations of potential risk factors, including sex, age, obesity status (body mass index [BMI]: 25-30 kg/m2 as reference), education, smoking status, and diabetes mellitus with the incidence of cancers among the population. Incidence rate ratios (IRRs) with 95% confidence interval (CI) were also reported. RESULTS: During a median follow-up of 13.9 years, there were 130 and 129 incident cancers for men and women, respectively; the corresponding ASRs were 356.1 and 243.6 per 100,000 person-years, respectively. The three most incident cancers among men were gastrointestinal (GI) (ASR = 127.5), hematopoietic (ASR = 99.5), and reproductive system malignancies (ASR = 46.3). The most common incident cancers in women were breast cancer (ASR = 92.1), GI (ASR = 65.4), and reproductive system malignancies (ASR = 16.8). Among risk factors for cancer incidence, age (IRR [95% CI]: 1.05 [1.03-1.06]) and having a BMI < 25 kg/m2 (IRR [95% CI]: 1.38 [1.01-1.90]) had a statistically significant association with incident cancer. CONCLUSIONS: The high rates of cancers in Tehran during more than a decade of follow-up calls for a need to define risk factors as well as to implement programs for early screening.

Adult genitourinary sarcoma: A population-based analysis of clinical characteristics and survival.

BACKGROUND: Sarcomas of the genitourinary (GU) tract are exceedingly rare, accounting for just 1% to 2% of malignancies treated by urologic surgeons. We perform a thorough investigation of incidence and mortality in the United States using the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: The SEER 18 database was used to identify patients diagnosed with genitourinary sarcoma over the age of 16. Data on demographics and tumor characteristics were collected. Survival analysis was performed on the most common primary tumor sites. RESULTS: The search identified 3,007 patients with GU sarcomas from 1973 to 2015. In order of descending incidence, tumors presented in the bladder, kidney, paratestis, and scrotum. Amongst sarcomas arising in the bladder, leiomyosarcomas exhibited the longest median survival time (overall survival (OS) 62 months), while carcinosarcomas had the shortest (OS 9 months). Metastatic disease decreased leiomyosarcoma OS to 3 months. When comparing renal tumors, liposarcomas had the longest median survival time (OS 45 months) and carcinosarcomas had the shortest (OS 6 months). Older age (P < 0.001 and P = 0.015) and T4 disease (P = 0.005 and P < 0.001) predicted for worse survival amongst bladder and renal sarcomas, respectively. High tumor grade (P < 0.001) and node positive disease (P = 0.024) also affected survival amongst renal tumors. CONCLUSIONS: Tumors most commonly present in the bladder, kidney, paratestis, and scrotum, with kidney sarcomas having markedly dismal survival outcomes. Survival of identical histologic types varied by primary tumor location, suggesting that treatment strategies should be refined by type of sarcoma and primary tumor location within the GU tract.

Survival outcomes of mucosal melanoma in the USA.

Background: Mucosal melanomas (MM) arise within the lining of the gastrointestinal (GI), genitourinary (GU) and head and neck (HN) systems. Method: A retrospective analysis of the National Comprehensive Database identified 4,961 MM patients. Primary objective was to compare survival outcomes across the different locations. Results: Overall survival for GI melanomas was significantly shorter than HN and GU melanomas. Median survival (95% confidence interval) was 19.5 (18.0-21.5), 26.4 (24.9-28.3), and 43.9 (38.8-47.8), months for GI, HN and GU cases, respectively (p<0.0001). Conclusion: This is the largest study of MM in a US based population, demonstrating worse overall survival for GI MM in comparison to HN and GU melanomas.

[Clinical and prognostic analysis of single-center multidisciplinary treatment for rhabdomyosarcoma in children].

Objective: To summarize the clinical characteristics, treatment response and prognostic factors of rhabdomyosarcoma (RMS) in children. Methods: The clinical characteristics such as age at diagnosis, primary tumor site, tumor size, pathological type, clinical stage, and risk grouping of 213 RMS patients (140 males and 73 females) treated in Hematology Oncology Center of Beijing Children's Hospital, Capital Medical University, from May 2006 to June 2018 were analyzed retrospectively. The clinical characteristics, overall survival (OS), event free survival (EFS) and prognostic factors of children treated with the Beijing Children's Hospital-Rhabdomyosarcoma (BCH-RMS) regimen were analyzed. Survival data were analyzed by Kaplan-Meier survival analysis, and single factor analysis was performed by Log-Rank test. Results: The diagnostic age of 213 cases was 48.0 months (ranged 3.0-187.5 months), of which 136 cases (63.8%) were younger than 10 years old. The head and neck region was the most common primary site of tumor (30%, 64 cases), followed by the genitourinary tract (26.8%, 57 cases). Among pathological subtypes, embryonal RMS accounted for 71.4% (152 cases), while alveolar RMS and anaplastic RMS accounted for only 26.8% (57 cases) and 1.9% (4 cases), respectively. According to the Intergroup Rhabdomyosarcoma Study Group (IRS), IRS-Ⅲ and Ⅳ accounted for 85.0% (181 cases) of all RMS patients. In all patients, 9.4% (20 cases) patients were divided in to low-risk group, 52.1% (111 cases) patients in to intermediate -risk group, 25.8% (55 cases) patients in to high-risk group, and 12.7% (27 cases) patients in to the central nervous system invasion group, respectively. All patients with RMS received chemotherapy. The cycles of chemotherapy were 13.5 (ranged 5.0-18.0) for patients without event occurrence, while 14.2 (ranged 3.0-30.0) for patients with event occurrence. Among the 213 patients, 200 patients had surgical operation, of whom 103 patients underwent surgery before chemotherapy and 97 patients at the end of chemotherapy, 21 patients had secondary surgical resection. Radiotherapy was performed in 114 patients. The follow-up time was 23.0 months (ranged 0.5-151.0 months) . There were 98 patients with relapsed or progressed disease and 67 patients with death. The median time to progression was 10 months, of which 67 (68.4%) relapse occurred within 1 year and no recurrence occurred after follow-up for more than 5 years. The 3-year EFS and 5-year EFS were (52±4) % and (48±4) %, while the 3-year OS and 5-year OS were (65±4) % and (64±4) % by survival analysis. The 5-year OS of the low-risk, intermediate-risk, the high-risk were 100%, (74±5) %, (48±8) %, and the 2-year OS of the central nervous system invasion group was (36±11) % (χ(2)=33.52, P<0.01). The 5-year EFS of the low-risk, intermediate-risk, the high-risk were (93±6) %, (51±5) %, (36±7) % and the 2-year EFS of the central nervous system invasion group was (31±10) % (χ(2)=24.73, P<0.01) . Survival factor analysis suggested that the OS of children was correlated with age(χ(2)=4.16, P=0.038), tumor TNM stage (χ(2)=22.02, P=0.001), IRS group (χ(2)=4.49, P<0.01) and the risk group (χ(2)=33.52, P<0.01). Conclusions: This study showed that the median age of newly diagnosed RMS patients was 4 years. The head and neck and the genitourinary tract were the most common primary origin of RMS. The OS was low in single-center RMS children. The median time to recurrence was 10 months, and recurrence was rare 3 years later.

Evolution of pelvic exenteration surgery- resectional trends and survival outcomes over three decades.

OBJECTIVE: To examine the changes in exenterative surgery over three decades analysing oncological outcomes and whether changes in surgical approach have led to improved patient outcomes. BACKGROUND: Advances in surgical technology, perioperative care and pattern of disease recurrence have coincided with an evolutionary change in exenterative surgery. METHODS: A review of a prospectively maintained databases of pelvic exenteration surgery from 1988 to 2018  at two high volume specialised institutions. The total cohort was divided into three major time points (1988-2004, 2005-2010 and 2011 to 2018) to allow comparative analysis. Primary endpoints were overall survival in primary and recurrent disease at each time point. Secondary endpoints included anastomotic leak, blood transfusion, ileus, wound infection rates and evolution of case complexity. Data were analysed using R with a p < 0.05 considered significant. RESULTS: Six hundred and seventy patients underwent exenterative surgery. In 2011-2018 there was an increase in resection of recurrent malignancy with a continuous increase in GI malignancies resected over each time period(p < 0.001,<0.01) and a reduction in gynaecological malignancy(p < 0.001). A significant increase in sacrectomy, pelvic sidewall resection and ileal conduit reconstruction was observed (p < 0.01,<0.001).In 2005-2010 patients had increased rates of ileus and anastomotic leak(p < 0.05). Patients undergoing resection for primary disease had improved overall survival at time points 1988-2004 and 2011-2018 compared to those with recurrent disease(p = 0.007,<0.001). Overall survival was significantly improved in patients with primary versus recurrent disease(p = 0.022). CONCLUSION: There has been a significant improvement in survival in patients undergoing pelvic exenteration surgery from primary disease. Case complexity has increased without significant morbidity.

Impact of Centralizing Care for Genitourinary Malignancies to High-volume Providers: A Systematic Review.

CONTEXT: The centralization of cancer care is associated with better clinical outcomes and may be a method for optimizing value-based health care systems. OBJECTIVE: To systematically review the literature regarding the impact of centralization of care on clinical outcomes for genitourinary malignancies. EVIDENCE ACQUISITION: A systematic review was conducted using Ovid and MEDLINE to identify studies between 1970 and 2018 reporting on the centralization of care for genitourinary malignancies. Prospective and retrospective studies were screened. EVIDENCE SYNTHESIS: There were no published randomized control trials (RCTs) on the centralization of care for genitourinary malignancies. Twenty-two retrospective studies met inclusion criteria. Centralization of radical cystectomy was the most studied. Care for bladder cancer, prostate cancer, penile cancer, testicular cancer, and renal cancer was reportedly associated with better morbidity and survival outcomes for patients treated at high-volume centers. However, evidence of better outcomes for centralization of care remains limited for penile, renal, and testicular cancers owing to the paucity of data and/or the lower incidence of these genitourinary malignancies. CONCLUSIONS: Care for genitourinary malignancies by high-volume providers was associated with greater utilization of cancer surgery, lower morbidity, and better survival outcomes. Centralization of care was most appropriate for complex procedures such as radical cystectomy when interpreted in the context of survival outcomes. Further research is needed to address the impact of centralizing care for all urologic malignancies with consideration of the associated costs and patient-reported measures, including quality of life and patient experience. PATIENT SUMMARY: We explored the evidence for moving major operations into larger centers. We focused on surgery for cancers of the bladder, prostate, testicle, penis, and kidney, and found that larger-volume hospitals had better survival outcomes and fewer complications when compared to smaller hospitals. The difference may be greatest for complex major surgeries such as radical cystectomy.

Risk and outcomes of second malignant neoplasms in chronic myeloid leukemia survivors.

The risk of second malignant neoplasms (SMN) in chronic myeloid leukemia (CML) survivors remains unclear. We utilized the Surveillance, Epidemiology and End Results 18 (SEER 18) registries to evaluate the risk and subsequent outcomes of SMN in CML survivors. There were 3407 patients included. Of these, 170 (4.99%) developed a SMN with SIR of 1.40 (95% C.I. 1.19-1.62). An increased risk was noted for cancers of the respiratory tract, genitourinary (GU) tract and skin excluding basal cell and squamous cell carcinoma. Using 3:1 matching (3 de novo malignancies to 1 post-CML SMN case), we compared survival data for cancers of the respiratory, GU and gastrointestinal (GI) tract. Patients with GU malignancies developing after CML had worse overall survival than patients without prior CML diagnosis (P = 0.018). There was no difference in survival between post-CML and non-post-CML patients with respiratory or GI malignancies.

Smokeless tobacco mortality risks: an analysis of two contemporary nationally representative longitudinal mortality studies.

BACKGROUND: Assessments supporting smokeless tobacco (SLT) disease risk are generally decades old. Newer epidemiological data may more accurately represent the health risks associated with contemporary US-based SLT products, many of which contain lower levels of hazardous and potentially hazardous chemicals compared to previously available SLT products. METHODS: Data from two longitudinal datasets (National Longitudinal Mortality Study-NLMS, and the National Health Interview Survey-NHIS) were analyzed to determine potential associations between SLT use and/or cigarette smoking and all-cause and disease-specific mortality. Mortality hazard ratios (HR) were estimated using a Cox proportional hazards regression model applied to various groups, including never users of any tobacco or SLT product, and current and former SLT users and/or cigarette smokers. RESULTS: The two datasets yielded consistent findings with similar patterns evident for the specific causes of death measured. All-cause mortality risk for exclusive SLT users was significantly lower than that observed for exclusive cigarette smokers and dual SLT/cigarette users. Similar trends were found for mortality from diseases of the heart, chronic lower respiratory diseases, and malignant neoplasms. Mortality risk for lung cancer in exclusive cigarette smokers was increased by about 12-fold over never-tobacco users but was rarely present in exclusive SLT users in either survey (NHIS, < 5 cases/1,563 observations; NLMS, 3 cases/1,863 observations). While the data in the surveys are limited, SLT use by former cigarette smokers was not associated with an increase in the lung cancer risk HR compared to that by former cigarette smokers who never used SLT. CONCLUSIONS: Emerging epidemiological data provides a new perspective on the health risks of SLT use compared to risks associated with cigarette smoking. HR estimates derived from two current US datasets, which include data on contemporary tobacco products, demonstrate a clear mortality risk differential between modern SLT products and cigarettes. Cigarette smokers had an increased overall mortality risk and risk for several disease-specific causes of death, while SLT users consistently had lower mortality risks.