Age related differences in primary testicular lymphoma: A population based cohort study

IntroductionPrimary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50.MethodsThe SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared.ResultsThere was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1–50), and 72 (IQR 51–95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57–0.71) and 0.34 (95% CI: 0.31–0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25–6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26–0.40) compared to HR of 0.40 (95% CI: 0.37–0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05– 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM.ConclusionsPTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival.     

Predictive factors for mortality after distal femoral fractures in the elderly: A retrospective multicenter (TRON group) study

PurposeThis retrospective multicenter study aimed to assess the 1-year mortality rate in elderly patients with distal femoral fractures (DFFs) and identify potential risk factors for mortality.MethodsWe analyzed 321 patients aged 65 years and older with DFFs treated surgically between 2012 and 2019 in 13 hospitals. Patient demographics and surgical characteristics were extracted from medical records and radiographs. We used univariable and multivariable Cox regression analyses to identify the factors affecting mortality.ResultsThe mortality rate for DFFs in elderly patients at 1 year was 9.0%. Multivariable Cox regression analysis revealed older age, male sex, underweight (body mass index [BMI] <18.5 kg/m²), bedridden status, and nursing home residency to be independent predictors for mortality (older age: hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.03–1.11, P<0.001; male sex: HR 3.08, 95% CI 1.23–7.71, P=0.015; underweight: HR 1.93, 95% CI 1.01–3.68, P=0.045; bedridden status: HR 4.59, 95% CI 1.61–13.07, P=0.0042; and nursing home residency: HR 2.63, 95% CI 1.18–5.83, P=0.017). None of the factors associated with surgery including types of fixation, time from initial visit to surgery, blood loss during operation, and operation time was an independent predictor for mortality.ConclusionThe 1-year mortality rate in elderly patients with DFFs was relatively low at 9.0%. Older age, lower BMI, and nursing home residency were associated with mortality after surgery for DFFs. Factors associated with the surgical procedure were not significant predictors.     

Survival benefit of chemotherapy in a contemporary cohort of metastatic urachal carcinoma

BackgroundWe relied on the most contemporary Surveillance, Epidemiology, and End Results (SEER) database and tested the hypothesis that chemotherapy may improve survival in metastatic urachal carcinoma (m-UraC).Material and MethodsWithin the SEER database (2004–2016), we identified m-UraC patients aged ≥ 18 years. Propensity score matching (PSM: cystectomy status, age and sex), Kaplan-Meier plots, cumulative incidence plots, Cox regression models and competing risks regression (CRR) models addressed overall mortality (OM) and cancer-specific mortality (CSM).ResultsOverall, 274 m-UraC patients were identified with a median age of 70 years. Most were male (66%) and Caucasian (72%). Overall, 32% received chemotherapy. Chemotherapy-exposed patients were younger (62 vs. 73 years, p<0.001) and more frequently underwent cystectomy (19 vs. 8%, P = 0.014). In 274 m-UraC patients, median OM and CSM were 6 (4 –10) months and 8 (6 –14) months, respectively. After 1:1 PSM, chemotherapy-exposed patients exhibited lower OM (median 16 vs. 3 months; multivariable HR 0.38, P <0.001) and lower CSM (median 17 vs. 4 months; multivariable CRR HR 0.52, P = 0.001). The association between chemotherapy and better survival was even stronger in younger (≤70 years) patients (OM HR: 0.23, P <0.001; CSM CRR HR: 0.42, P = 0.001), but not in older (≥71 years) patients (OM HR: 0.61, P = 0.2; CSM CRR HR: 1.02, P = 1), after PSM and multivariable adjustments.ConclusionOverall, we validated the very aggressive nature of UraC, when distant metastases are present, and observed that m-UraC patients exposed to chemotherapy exhibited lower OM and CSM.     

Impact of inhalation injury on outcomes in critically ill burns patients: 12-year experience at a regional burns centre

IntroductionBurns inhalation injury increases the attributable mortality of burns related trauma. However, diagnostic uncertainties around bronchoscopically graded severity, and its effect on outcomes, remain. This study evaluated the impact of different bronchoscopic burns inhalation injury grades on outcomes.MethodsA single-centre cohort study of all patients admitted to the London Burns centre intensive care unit (BICU) over 12 years. Demographic data, burn and burns inhalation injury characteristics, and ICU-related parameters were collected retrospectively. The primary outcome was mortality. Secondary outcomes were hospital and ICU lengths of stay. The impact of pneumonia was determined. Univariate and multivariable Cox’s proportional hazards regression analyses informed factors predicting mortality.ResultsBurns inhalation injury was diagnosed in 84 of 231 (36%) critically ill burns patients; 20 mild (grade 1), 41 severe (grades 2/3) and 23 unclassified bronchoscopically. Median (IQR) total body surface area burned (TBSA) was 20% (10?40). Mortality was significantly higher in patients with burns inhalation injury vs those without burns inhalation injury (38/84 [45%] vs 35/147 [24%], p < 0.001). Patients with pneumonia had a higher mortality than those without (34/125 [27%] vs 8/71 [11%], p = 0.009). In multivariable analysis, severe burns inhalation injury significantly increased mortality (adjusted HR=2.14, 95%CI: 1.12–4.09, p = 0.022), compared with mild injury (adjusted HR=0.58, 95% CI: 0.18–1.86, p = 0.363). Facial burns (adjusted HR=3.13, 95%CI: 1.69–5.79, p < 0.001), higher TBSA (adjusted HR=1.05, 95%CI: 1.04–1.06, p < 0.001) and older age (adjusted HR=1.04, 95%CI: 1.02–1.07, p < 0.001) also independently predicted mortality, though pneumonia did not.ConclusionsSevere burns inhalation injury is a significant risk factor for mortality in critically ill burns patients. However, pneumonia did not increase mortality from burns inhalation injury. This work confirms prior implications of bronchoscopically graded burns inhalation injury. Further study is suggested, through registries, into the diagnostic accuracy and reliability of bronchoscopy in burns related lung injury.     

Pre-operative factors associated with increased mortality in elderly patients with a hip fracture: A cohort study in a developing country

BackgroundHip fractures are a public health problem worldwide, and several factors are involved with post-operative mortality. The aim of this study was to identify the pre-operative factors associated with increased mortality in elderly patients with hip fractures in a developing country during the first post-operative year.MethodsAn ambidirectional cohort study was conducted with patients ≥ 65 years of age who underwent hip surgery due to a hip fracture caused by a fall from a standing position. Socio-demographic data, time to surgery, and comorbidities measured by the Charlson Comorbidity Index (CCI) were recorded. One-year mortality from all causes was the primary outcome, and 30-day and 6-month mortality were the secondary outcomes. Log-rank test was used to evaluate survival, and Cox’s proportional hazard regression was used to detect the factors associated with increased mortality.Results478 patients who underwent hip surgery were included in this study. The mean age was 80.2 ± 9.9, and 297 (62%) were females. There were 150 (31.4%) deaths at the end of the first follow-up year, and the mean of surgical delay was 8.8 days ± 6.4. Patients who underwent surgery during the first 4 days (Log-rank test < 0.001) after hip fracture occurred and patients with a CCI ≤ 2 (Log-rank test < 0.001) showed better survival (90%), comparing to mortality (52%) of patients with a CCI ≥ 3 and surgical delay > 4 days. The age ≥ 80 years (Hazard ratio 2.55 (HR), 95% confidence interval (CI) 1.70 to 3.84, p < 0.001), CCI ≥ 3 (HR 1.61, 95% CI 1.14–2.26, p 0.006), surgical delay > 4 days (HR 2.41, 95% CI 1.38–4.21, p 0.006), and haemoglobin < 10 g/dl (HR 1.51, 95% CI 1.06–2.15, p 0.02) were associated with increased 1-year mortality. In addition, 30-day mortality was associated with age ≥ 80 years (HR 4.15, 95% CI 1.98–8.70, p < 0.001), CCI ≥ 3 (HR 1.80, 95% CI 1.08–2.99, p 0.023), pre-surgical time >48 h (HR 3.0, 95% CI 1.58–5.92, p 0.001), and surgical delay > 4 days (HR 3.0, 95% CI 1.33–6.81, p 0.008); and 6-month mortality was associated with surgical delay > 4 days (HR 2.72, 95% CI 1.42–5.23, p 0.003), and haemoglobin < 10 g/dl (HR 1.56, 95% CI 1.04–2.33, p < 0.028).ConclusionsSurgical delay greater than 4 days and Charlson Comorbidity Index ≥ 3 were found as factors associated with increased mortality, along with anaemia < 10 g/dl and age ≥ 80 years. A similar mortality rate was found in this study compared to the rates reported by the literature, despite a surgical delay of 8.8 days.     

Contemporary analysis of the effect of marital status on survival in upper tract urothelial carcinoma patients treated with radical nephroureterectomy: A population-based study

PurposeUnmarried status is an established risk factor for worse cancer control outcomes in various malignancies. Moreover, several investigators observed worse outcomes in unmarried males, but not in females. This concept has not been tested in upper tract urothelial carcinoma and represents the topic of the study.MethodsWithin Surveillance, Epidemiology and End Results database (2004–2016), we identified 8833 non-metastatic upper tract urothelial carcinoma patients treated with radical nephroureterectomy (5208 males vs. 3625 females). Kaplan Meier plots and multivariable Cox regression models predicting overall mortality, other-cause mortality and cancer-specific mortality were used.ResultsOverall, 1323 males (25.4%) and 1986 females (54.8%) were unmarried. Except for lower rates of chemotherapy in unmarried males (15.6 vs. 19.6%, P = 0.001) and unmarried females (13.8 vs. 23.6%, P < 0.001), no clinically meaningful differences were recorded between males and females. In multivariable Cox regression models, unmarried status was an independent predictor of higher overall mortality in both males (Hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.19–1.48, P < 0.001) and females (HR: 1.13, 95%CI: 1.00–1.27, P = 0.04), as well as of higher other-cause mortality in both males (HR: 1.53, 95%CI: 1.26–1.84,P < 0.001) and females (HR: 1.43, 95%CI: 1.15–1.78,P < 0.01). However, higher cancer-specific mortality was only recorded in unmarried males (HR: 1.24, 95%CI: 1.08–1.42, P < 0.01), but not in females (HR: 1.02, 95%CI: 0.89–1.17, P = 0.7).ConclusionUnmarried status is a marker of worse survival in both males and females and should be flagged as an important risk factor at diagnosis, in both sexes. In consequence, unmarried patients represent candidate for interventions aimed at decreasing the survival gap relative to married counterparts.     

Survival of nonseminomatous germ cell tumors in pediatric patients and young adults – A stage group stratified analysis

IntroductionTesticular germ cell tumors, particularly nonseminomatous germ cell tumors (NSGCT), comprise the most common solid malignancy in male children and younger adults. While these patients experience excellent survival outcomes, few studies have characterized their survival by age. Thus, we aimed to characterize the relative survival of NSGCT by age, stratifying patients by stage group.MethodsUsing the Surveillance Epidemiology and End Results (SEER) database, we divided patients with NSGCT into pediatric patients and adolescents (<19 years), young adults (19–30 years), and older adults (>30 years). Survival analysis, using Cox proportional hazards models and Kaplan Meier curves, described overall and cancer-specific survival (CSS) of each age category for Stage I-III NSGCT by stage group.ResultsA total of 14,786 patients met inclusion criteria and comprised the age groups <19 years (N=1,287), 19 to 30 years (N=7,729), and >30 years (N=5,770). Stage group distribution at presentation was similar between each group. Survival analysis demonstrated no differences in cancer-specific survival (CSS) among Stage I or II NSGCT. However, among Stage III tumors, multivariable models noted worse CSS in patients >30 years (HR=3.35 (95%CI: 1.45–7.73), P=0.005) and those 19-30 years (HR=2.28 (95%CI: 0.99–5.21), P=0.053) compared to pediatric and adolescent patients.ConclusionsYounger NSGCT patients experience excellent oncologic outcomes compared to their older counterparts. These survival differences by age group are largely driven by differential survival among Stage III neoplasms. Furthermore, our report lends additional evidence that age is an important prognostic factor in advanced NSGCT, including pediatric and adolescent patients.     

Identification of oncological characteristics associated with improved overall survival in patients with adrenocortical carcinoma treated with adjuvant radiation therapy: Insights from the National Cancer Database

ObjectivesTo test for an association between oncological risk factors and overall survival in patients with non-metastatic adrenocortical carcinoma treated with adjuvant radiation therapy at high-risk for recurrence per NCCN guidelines.Materials and MethodsWe analyzed data from patients undergoing surgical resection with or without aRT in the NCDB from 2004 to 2017. A multivariable Cox proportional hazards model was fit to assess for an association of aRT and OS. To determine whether aRT was associated with improved OS in patients with specific NCCN risk factors, we fit three multivariable Cox proportional hazard models with an interaction term between NCCN risk factors and the use of aRT.ResultsWe identified 1,433 patients treated surgically for adrenocortical carcinoma with at least one risk factor. 259 patients received adjuvant radiation therapy (18%) while 1,174 (82%) patients did not. After adjustment, we noted a significant association between adjuvant radiation therapy and overall survival in the entire cohort in the multivariable Cox proportional hazards model (HR 0.68, 95% CI 0.55–0.85, P = 0.001). Adjuvant radiation therapy was associated with increased overall survival in patients with positive surgical margins (HR 0.47, 95% CI 0.35–0.65, P < 0.001), large tumor size ≥6 cm (HR 0.69, 95% CI 0.55–0.87, P = 0.002), and high-grade disease (HR 0.61, 95% CI 0.37–0.99, P = 0.046).ConclusionsPatients with ACC at high-risk for recurrence were associated with improved overall survival when treated with adjuvant radiation therapy. These data may help identify which patients should consider aRT after resection of clinically localized ACC.     

Metastatic small cell carcinoma of the prostate: Population-based analysis of patient characteristics and treatment paradigms

IntroductionSmall cell carcinoma of the prostate is a rare malignancy comprising<1% of prostate cancers. Little is known about population-based treatment patterns for metastatic small cell carcinoma of the prostate. We evaluated clinical characteristics, treatment patterns, and survival outcomes.MethodsUsing the National Cancer Database, we identified patients between 1998 and 2011 diagnosed with pure small cell carcinoma of the prostate as their only malignancy who presented with nodal involvement or distant metastasis.ResultsTreatment information was available for 379 patients. Of them, 122 (32.5%) underwent chemotherapy (CT) alone, 25 (6.7%) received hormonal therapy (androgen-deprivation therapy) alone, 10 (2.7%) underwent radiation therapy alone, 3 (1%) underwent radical prostatectomy, and 167 (44.4%) underwent combination therapy. The 1- and 3-year survival rates were 35.3% and 4.4%, respectively. Those receiving any CT as part of their treatment had a median survival of 9.3 vs. 3.2 months for those not receiving it (P<0.001). Those receiving CT, androgen-deprivation therapy, and radiation had a median survival of 15.1 vs. 7 months for those receiving CT alone (P<0.001). On multivariable analysis (controlling for age, Charlson comorbidity index, extent of metastasis, prostate-specific antigen level, and type of treatment), older age (hazard ratio [HR] = 3.87; 95% CI: 1.41–9.34; P = 0.007) and distant metastatic disease (HR = 7.17; 95% CI: 1.62–31.8; P = 0.010) increased risk of death, whereas receipt of CT (HR = 0.15; 95% CI: 0.05–0.44; P = 0.001) decreased risk of death.ConclusionMen presenting with metastatic small cell carcinoma of the prostate have poor overall survival. Older patients and those presenting with distant metastases have an increased risk of death. It appears that patients receiving CT experience a modest survival benefit. The role of hormonal therapy in this population remains unclear.     

Impact of sarcopenia on outcomes of patients treated with trimodal therapy for muscle invasive bladder cancer

ObjectiveWe sought to investigate the incidence of sarcopenia and its impact on main oncological outcomes in patients with muscle invasive bladder cancer (MIBC) treated with trimodal therapy (TMT).Patients and MethodsThis was a retrospective analysis of 141 MIBC patients treated with TMT in the period 2002 to 2018. Sarcopenia was identified through pretreatment computed tomography scans and defined as a skeletal muscle index of <55 cm²/m² for men and <39 cm²/m² for women. Body mass index (BMI)-adjusted definition of sarcopenia was used to evaluate for sarcopenic obesity. Uni- and multivariable analyses were performed to assess the impact of sarcopenia on initial complete response and overall survival (OS) to TMT.ResultsMedian age at diagnosis was 73 years [range: 65–81] and median follow up was 32 months (Inter Quartile Range: 18–66). Median OS was 67 months (95% CI: 53–83). The incidence of sarcopenia and BMI-adjusted sarcopenia was 56.7% and 40.4%, respectively. On multivariable analysis, Eastern Cooperative Oncology Group performance status (HR = 2.37, 95% CI: 2.1–5.67, P = 0.001) and complete response to treatment (HR = 0.26, 95% CI: 0.14–0.049, P = 0.001] were independently associated with improved OS. Sarcopenia and BMI-adjusted sarcopenia were not independently associated with either complete response to TMT or OS. Similarly, in a subpopulation of 74 patients considered fit for radical cystectomy, we found that neither sarcopenia (P = 0.49) nor BMI-adjusted sarcopenia (P = 0.22) had an impact on OS.ConclusionSarcopenia and BMI-adjusted sarcopenia are prevalent in patients with MIBC undergoing TMT. TMT is a suitable treatment modality for patients with MIBC irrespective of their sarcopenia status.     

Breast conservative surgery for well-differentiated ductal intraepithelial neoplasia: Risk factors for ipsilateral breast tumor recurrence

RationalWe retrospectively analyzed 232 patients affected by well differentiated ductal intraepithelial neoplasia (DIN1c or DCIS G1) treated with conservative surgery without adjuvant radiotherapy.Results25 invasive and 18 non-invasive local recurrences were observed (median follow-up 80 months; 5-year cumulative incidence: 12.2%). Seven of the 15 young patients (<40 y) developed local recurrence (2 in situ, 5 invasive). Age <50 (HR 1.89, 95% C.I. 1.01–3.45), multifocality (HR 3.21, 95% C.I. 1.46–7.06), Ki-67 > 7% (HR 2.33, 95% C.I. 1.20–4.55) and surgical margins <10 mm (HR 2.00, 95% C.I. 1.06–3.76) were significantly associated with an increased risk of local recurrence.ConclusionsYoung age, multifocality and small margins appeared as clear risk factors of local recurrence in DIN1c (DCIS G1) population. The presence of multiple poor prognostic features warrant a thorough discussion regarding local treatment.     

Sarcopenia as a predictor of postoperative outcomes after urologic oncology surgery: A systematic review and meta-analysis

AimSarcopenia as a reliable prognostic predictor in urologic oncology surgery remains controversial, and no consensus amongst researchers exists regarding the management of patients with sarcopenia. This meta-analysis was conducted to investigate the association between sarcopenia and postoperative outcomes after urologic oncology surgery.MethodsA systematic search in MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library databases was conducted to identify the potential studies published before August 2019. Odds ratios and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated through inverse variance with random or fixed effects models.ResultsSeventeen retrospective cohorts comprising 3,948 patients were included with sarcopenia prevalence between 25% and 68.9%. Patients with sarcopenia had significantly shorter overall survival (OS; HR = 2.06, 95% CI: 1.44–2.95; P < 0.001; I-square (I²) = 86%) and cancer-specific survival (HR = 2.16, 95% CI: 1.60–2.92; P < 0.001; I² = 49.4%) than those without sarcopenia. Sarcopenia was independently associated with increased all-cause mortality (HR = 1.50, 95% CI: 1.26–1.80; P < 0.001; I² = 0%) and cancer-specific mortality (HR = 1.50, 95% CI: 1.12–2.01; P = 0.006; I² = 0%). No prognostic difference was observed in the postoperative risk of total complications and systemic progression except lymphovascular invasion status.ConclusionsSarcopenia is an independent poor prognostic factor for patients undergoing urologic oncology surgery, particularly postoperative risks of short survival and increased mortality. Thus, preoperative sarcopenia evaluation can provide clinicians with important information to guide and individualise patient management and improve surgical outcomes.     

Degree of hydronephrosis predicts adverse pathological features and worse oncologic outcomes in patients with high-grade urothelial carcinoma of the upper urinary tract

ObjectiveTo evaluate degree of hydronephrosis (HN) as a surrogate for adverse pathological features and oncologic outcomes in patients with high-grade (HG) and low-grade (LG) upper tract urothelial carcinomas (UTUCs).MethodsWe retrospectively reviewed 141 patients with localized UTUCs that underwent extirpative surgery at a tertiary referral center. Preoperative imaging was used to evaluate presence and degree of ipsilateral HN. We evaluated degree of HN (none/mild vs. moderate/severe), pathological findings, and oncologic outcomes.ResultsHG UTUC was present in 113 (80%) patients, muscle-invasive disease (≥pT2) in 49 (35%), and non–organ-confined disease (≥pT3) in 41 (29%). At a median follow-up of 34 months, 49 (35%) patients experienced intravesical recurrence, 28 (20%) developed local/systemic recurrence, and 24 (17%) died of UTUC. HN was graded as none/mild in 77 (55%) patients and moderate/severe in 64 (45%). In patients with HG UTUC, but not LG, degree of HN was associated with advanced pathological stage (P<0.001), positive lymph nodes (P = 0.01), local/systemic recurrence-free survival (hazard ratio [HR] = 5.5, P = 0.02), and cancer-specific survival (HR = 5.2, P = 0.02). On multivariable analysis of preoperative factors, degree of HN in patients with HG UTUC was associated with muscle invasion (HR = 9.3; 95% CI: 3.08–28.32; P<0.001), non–organ-confined disease (HR = 4.5; 95% CI: 1.66–12.06; P = 0.003), local/systemic recurrence-free survival (HR = 2.5; 95% CI: 1.07–5.64; P = 0.04), and cancer-specific survival (HR = 2.6; 95% CI: 1.05–6.22; P = 0.04).ConclusionsDegree of HN can serve as a surrogate for advanced disease and predict worse oncologic outcomes in HG UTUC. Degree of HN was not predictive of intravesical or local/systemic recurrence in LG UTUC.     

Breast cancer in young women: Pathologic features and molecular phenotype

PurposeControversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications.MethodsWe conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected.Results5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p < 0.01). A young age ≤40 years (p < 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60–2.63) or ≤35 years (p < 0.001; [HR]: 3.86; 95% [CL]: 2.69–5.53) impacted on the indication of chemotherapy. Age ≤35 (p < 0.001; [HR]: 2.01; 95% [CL]: 1.36–2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p < 0.006; [HR]: 0.6; 95% [CL]: 0.40–0.86) and positive hormone receptor status (p < 0.001; [HR]: 0.6; 95% [CL]: 0.54–0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35–40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p < 0.01).ConclusionYoung women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.     

Impact of preoperative serum albumin-globulin ratio on disease outcome after radical cystectomy for urothelial carcinoma of the bladder

IntroductionThe Albumin-Globulin Ratio (AGR; albumin/total protein ? albumin) has been associated with oncological outcome in various malignancies. However, its role in urothelial carcinoma of the bladder (UCB) has not been clearly established. In this study, we assessed the association of preoperative AGR (pAGR) with survival in patients who underwent radical cystectomy (RC) for UCB.Material and MethodsWe conducted a retrospective analysis of an established multicenter database of 4.335 patients who were treated with RC for UCB. The cohort was divided into 2 groups according to the pAGR status. Binominal logistic regression as well as uni- and multivariable Cox regression analyses were used. The predictive value of the models was assessed by calculating receiver operating characteristics curves and concordance-indices (C-Index). The additional clinical value was assessed using the decision curve analysis (DCA).ResultsOverall, 1.670 patients (38.5%) had a low pAGR. On multivariable logistic regression analyses, low pAGR was associated with an increased risk of ≥pT3 disease at RC (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01–1.31, P= 0.04). On multivariable Cox regression analyses, low pAGR remained associated with worse recurrence-free survival (RFS, HR 1.24, 95% CI 1.1–1.37, P< 0.001), cancer-specific survival (CSS, HR 1.23, 95% CI 1.1–1.38, P< 0.001) and overall survival (OS, HR 1.17, 95% CI 1.07–1.28, P< 0.001). The addition of pAGR to multiple prognostic models that were respectively fitted for clinical and postoperative variables did not improve the predictive accuracy.ConclusionpAGR status is an independent predictor of ≥pT3 disease, therefore it could help identify patients who have a higher likelihood to benefit from neoadjuvant systemic therapy. While pAGR was independently associated with RFS, CSS, and OS, it did not improve the predictive accuracy and clinical value beyond obtained by information already available. The predictive value of this biomarker in the age of immunotherapy needs further evaluation.     

Association between weight loss and serum biomarkers with risk of incident cancer in the Longitudinal Assessment of Bariatric Surgery cohort

BackgroundBariatric surgery reduces cancer risk in populations with obesity. It is unclear if weight loss alone or metabolic changes related to bariatric surgery cause this effect.ObjectiveWe evaluated the relationship between surgical weight loss and serum biomarker changes with incident cancer in a bariatric surgery cohort.SettingTen U.S. clinical facilities.MethodsThe Longitudinal Assessment of Bariatric Surgery 2 (LABS-2) is a prospective multicenter cohort (n = 2458, 79% female, mean age = 46). We evaluated weight and serum biomarkers, measured preoperatively and 1 year postoperatively, as predictors for incident cancer. Associations were determined using Cox proportional hazards models adjusting for weight loss, age, sex, education, and smoking history.ResultsOver 8759 person-years of follow-up, 82 patients reported new cancer diagnosis (936 per 100,000 person-years, 95% confidence interval [CI]: 749–1156). Cancer risk was decreased by approximately 50% in participants with 20% to 34.9% total weight loss (TWL) compared with <20% TWL (hazard ratio [HR] = .49, 95%CI: .29–.83). Reduced cancer risk was observed with percent decrease from baseline for glucose (per 10%, HR = .94, 95%CI: .90–.99), proinsulin (per 20%, HR = .95, 95%CI: .93–.98), insulin (per 30%, HR = .97, 95%CI: .96–.99), and leptin (per 20%, HR = .81, 95%CI: .68–.97), and per 15% percent increase in ghrelin (HR = .94, 95%CI: .29–.83).ConclusionsAfter bariatric surgery, cancer risk is reduced >50% when weight loss exceeds 20% TWL compared with patients with <20% TWL. Weight loss alone may not explain the observed risk reduction, as improvements in diabetes, leptin, and ghrelin were associated with decreased cancer risk.     

Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors

BackgroundThe association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial.Materials and methodsWe retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models.ResultsOverall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.28–3.18, P = 0.003) and iPFS (HR: 1.70, 95% CI: 1.23–2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR: 0.61, 95% CI: 0.36–1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR: 0.97, 95% CI: 0.93–1.00, P[interaction] = 0.048) and was increased in males (HR: 2.97, 95% CI: 1.10–8.05, P[interaction] = 0.032).ConclusionsPPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.     

Management of HR+/HER2+ lobular breast cancer and trends do not mirror better outcomes

PurposeTreatment protocols for invasive lobular breast cancer (ILC) have largely followed those for invasive ductal breast cancer. This study compares treatment outcomes of endocrine therapy versus combined chemo-endocrine therapy in hormone-receptor-positive (HR+), HER2-positive (HER2+) ILC tumors in a large national registry.MethodsWe sampled the National Cancer Database (2010–2016) for female patients with stages I-III, HR+/HER2+ ILC who underwent surgery. Cochran-Armitage trend test examined trends of treatment regimen administration: Surgery only (S), chemotherapy (C), endocrine therapy (ET), and combined chemo-endocrine therapy (CET), with or without anti-HER2 therapy. Cox proportional hazard model were used to compare overall survival (OS) across ET and CET cohorts, stratifying for anti-HER2 therapy, before and after propensity score match of cohorts (2013–2016). Kaplan-Meier (KM) survival curves were also produced.ResultsN=11,421 were included. 58.7% of patients received Anti-Her2 therapy after 2013. CET conferred better OS over ET in the unmatched (adjusted-5-year-OS: 92.5% vs. 81.1%, p<0.001) and PS-matched (90.4% vs. 84.5%, p=0.001) samples. ET caused lower OS in patients who received Anti-Her2 therapy (HR: 2.56, 95% CI: 1.60–4.12, p<0.001) and patients who did not (HR: 1.84, 95% CI: 1.21–2.78, p=0.004), as compared to CET on multivariable analysis. KM modeling showed highest OS in the CET cohort who received Anti-Her2 (93.0%), followed by the CET cohort who did not receive Anti-Her2 (90.2%) (p=0.06).ConclusionChemotherapy followed by endocrine therapy and Anti-Her2 therapy was shown to be the most effective treatment modality in HR+/HER2+ ILC, contrasting previous data on the inconclusive benefit of chemotherapy in patients with ILC.     

Impact of treatment modality on overall survival in localized ductal prostate adenocarcinoma: A national cancer database analysis

PurposeDuctal adenocarcinoma is considered a rare histological variant of prostate adenocarcinoma (PCa). Given the rarity of this subtype, optimal treatment strategies for men with nonmetastatic ductal PCa is largely unknown. We aimed to describe the impact of surgery, radiotherapy, systemic therapy, and observation on overall survival (OS) in men with nonmetastatic ductal PCa.Materials and methodsWe selected 1,656 cases of nonmetastatic ductal PCa, diagnosed between 2004 and 2015, within the National Cancer Database. Covariates included age, race, Charlson comorbidity score, clinical T stage, clinical lymph node stage, serum prostate specific antigen (PSA), income, hospital type, insurance status, year of diagnosis, and location of residence. Cox regression analysis tested the impact of treatment (surgery, radiotherapy, systemic therapy, and observation) on OS.ResultsIn men with nonmetastatic ductal PCa, median (interquartile range [IQR]) age and PSA were 67 (60–73) years and 6.2 (4.2–10.7) ng/ml, respectively. Advanced local stage (≥cT3a) was most frequently observed in patients initially treated with systemic therapy (34.8%), followed by those treated with radiotherapy (18.1%), surgery (7.1%) and observation (6.4%, P< 0.001). Serum PSA at presentation was highest in the systemic therapy cohort (median 16.0 ng/ml, IQR: 4.9–37.7), followed by the radiotherapy cohort (median 7.2 ng/ml, IQR: 4.1–12.2), observation cohort (median 7.0 ng/ml, IQR: 4.3–13.3) and surgery cohort (median 5.9 ng/ml, IQR: 4.3–9.2, P< 0.001). Multivariable analysis showed that in comparison to men treated surgically, OS was significantly lower for patients receiving radiotherapy (HR 2.2; 95% CI: 1.5–3.2), under observation (HR 4.6; 95% CI: 2.8–7.6) and receiving systemic therapy (HR 5.2; 95% CI: 3.0–9.1) as an initial course of treatment.ConclusionsWhile limited by its retrospective nature, our study shows that starting treatment with surgery is associated with more favorable long-term OS outcomes than radiotherapy, systemic therapy or observation.