Higher Risk Of Cancer-specific Mortality Research Articles

Alveolar Soft Part Sarcoma in the Female Genital Tract: Case Series with Literature Review and SEER Database Analysis.

Alveolar soft part sarcoma (ASPS) is a rare and distinct subtype of soft tissue sarcoma. This study aims to describe the unique presentation of ASPS in the female genital tract. Prognostic factors for cancer-specific overall survival (CSS) were evaluated using multivariate analyses. In our case series, we identified a novel TFE3-PRCC gene fusion in a 24-year-old unmarried patient with cervical ASPS who underwent fertility-sparing surgery and remained recurrence-free for 41 months. The other two patients underwent radical hysterectomy and bilateral salpingo-oophorectomy. At the time of writing, the two patients had been disease-free for 49 and 71 months, fluorescence in situ hybridization showed break-apart signals for the ASPL-TFE3 gene. Among the 55 cases with available information from the PubMed/Medline database, most presented with localized disease, and at the last follow-up, all patients were alive and 45 patients showed no evidence of disease. The 5-year CSS rate in the female genital tract cohort from SEER database was 86.2%. Multivariate analysis revealed that older age was associated with a 1.042-fold increased risk of cancer-specific mortality (HR=1.042, 95% CI 1.022-1.063, P < 0.001), involvement of soft tissue including the heart was associated with a 4.786-fold higher risk (HR=4.7868, 95% CI 1.681-13.623, P= 0.003), and regional infiltration and distant metastasis were associated with approximately 8.6-fold and 18-fold higher risk of cancer-specific mortality compared to local disease, respectively (HR=8.652, 95% CI 2.529-29.63, P = 0.001; HR=18.366, 95% CI 6.153-54.817, P< 0.001). Patients who underwent radical excision did not show reduced cancer-specific mortality compared to those who underwent local excision (HR=0.492, 95% CI 0.224-1.081, P = 0.078). Previously unrecognized genetic diversity exists in ASPS. Patients with ASPS in the female genital tract have the lowest likelihood of presenting with a distant disease and are associated with a more favorable survival outcome.

Associations of Fat Mass and Sarcopenia With All-Cause and Cancer-Specific Mortality in Cancer Survivors

Purpose of the study: The role of body composition in cancer outcomes is of great clinical interest. We investigated whether the risks of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Methods: Participants included 1682 adult cancer survivors who had undergone dual-energy x-ray absorptiometry (DXA) examination to measure body composition, gathered from the 1999–2006 and 2011–2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was defined by appendicular skeletal muscle mass index (females &amp;lt; 5.45 kg/m2 and males &amp;lt; 7.26 kg/m2). Multivariable Cox proportional hazards models were performed to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI); we also stratified by race. In addition, we performed a restricted cubic spline analysis to assess the potential non-linear association between fat mass and all-cause mortality. Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. Overall, sarcopenia was present in 304 (25.0%), and 561 (33.4%) of the participants had high total fat mass. Participants with higher fat mass had 30% increased risk of all-cause mortality (aHR = 1.30, 95% CI = 1.06–1.61) compared to participants with low fat mass, while participants with sarcopenia had a 51% higher risk (aHR = 1.51, 95% CI = 1.22–1.88) than participants with no sarcopenia. A restricted cubic spline analysis revealed a J-shaped association between fat mass and all-cause mortality. Further, sarcopenia was also associated with a higher risk of cancer-specific mortality (aHR = 1.74, 95% CI = 1.23–2.29) compared to non-sarcopenia. The association between sarcopenia and all-cause mortality was twice as strong in Non-Hispanic Blacks (aHR = 2.99, 95% CI = 1.39–6.06) compared to Non-Hispanic Whites (aHR = 1.53, 95% CI = 1.19–1.95). Conclusion: Our findings show opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors.

Racial disparities in nephrectomy and mortality among patients with renal cell carcinoma: Findings from SEER.

To assess racial differences in the receipt of nephrectomy in patients diagnosed RCC in the US. 2005 to 2015 data from the SEER database was analyzed and 70,059 patients with RCC were identified. We compared demographic and tumor characteristics between black patients and white patients. We applied logistic regression to assess the association between race and the odds of the receipt of nephrectomy. We also applied Cox proportional hazards model to assess the impact of race on cancer-specific mortality (CSM) and all-cause mortality (ACM) in patients diagnosed with RCC in the US. Black patients had 18% lower odds of receiving nephrectomy compared to white patients (p < 0.0001). The odds of the receipt of nephrectomy also reduced with age at diagnosis. In addition, patients with T3 stage had the greatest odds of receiving nephrectomy when compared to T1 (p < 0.0001). There was no difference in the risk of cancer-specific mortality between black patients and white patients; black patients had 27% greater odds of all-cause mortality than white patients (p < 0.0001). Patients who did not receive nephrectomy had a 42% and 35% higher risk of CSM and ACM respectively, when compared to patients who received nephrectomy. Black patients diagnosed with RCC in the US have a greater ACM risk and are less likely than white patients to receive nephrectomy. Systemic changes are needed to eliminate racial disparity in the treatment and outcomes of RCC in the US.

Cancer-Specific Mortality Differences in Specimen-Confined Radical Prostatectomy Patients According to Lymph Node Invasion

PurposeTo test cancer-specific mortality (CSM) differences in specimen-confined (pT2) prostate cancer (PCa) at radical prostatectomy (RP) with lymph node dissection (LND) according to lymph node invasion (LNI). MethodsRP + LND pT2 PCa patients were identified (surveillance, epidemiology, and end results 2010-2015). CSM-FS rates were tested in Kaplan-Meier plots and multivariable Cox-regression (MCR) models. Sensitivity analyses respectively addressing patients with 6 or more lymph nodes analyzed and pT2 pN1 patients were performed. ResultsOverall, 32,258 patients with pT2 PCa at RP + LND were identified. Of these, 448 (1.4%) patients harbored LNI. Five-year CSM-free estimates were 99.6% for pN0 vs. 96.4% for pN1 (P < .001). In MCR models, pN1 (HR: 3.4, P < .001) independently predicted higher CSM. In sensitivity analyses addressing patients with 6 or more lymph nodes analyzed (n = 15,437), 328 (2.1%) pN1 patients were identified. In this subgroup, 5-year CSM-free estimates were 99.6% for pN0 vs. 96.3% for pN1 (P < .001) and, in MCR models, pN1 independently predicted higher CSM (HR: 4.4, P < .001). In sensitivity analyses addressing pT2 pN1 patients, 5-year CSM-free estimates were 99.3, 100 and 84.8% for ISUP GG 1-3 vs. 4 vs. 5, respectively (P < .001). ConclusionsIn patients with pT2 PCa a small proportion harbor LNI (1.4%-2.1%). In such patients, CSM rate is higher (HR 3.4-4.4, P < .001). This higher CSM risk seems to virtually exclusively apply to ISUP GG5 patients (84.8% 5-year CSM-free rate).

Abstract 3036: Associations of total body fat mass and skeletal muscle index with all-cause and cancer-specific mortality in cancer survivors

Abstract Purpose of the Study: The purpose of the study was to investigate whether the risks of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Additionally, we conducted subgroup analysis to assess potential effect modification by race/ethnicity. The role of body composition in cancer outcomes is of great clinical interest, and measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. Methods: Participants included 1682 adult cancer survivors who had undergone dual-energy x-ray absorptiometry (DXA) examination to measure body composition, gathered from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass (weight of fat in the body) was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was defined by appendicular skeletal muscle mass index (females &amp;lt; 5.45kg/m2 and males &amp;lt; 7.26kg/m2). Multivariable Cox proportional hazards models were performed to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI); we also stratified by race. In addition, we performed a restricted cubic spline analysis to assess the potential non-linear association between fat mass and all-cause mortality. Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. Overall, sarcopenia was present in 304 (25.0%), and 561 (33.4%) of the participants had high total fat mass. Participants with higher fat mass had 30% increased risk of all-cause mortality (aHR=1.30, 95% CI=1.06-1.61) compared to participants with low-fat mass, while participants with sarcopenia had a 51% higher risk (aHR=1.51, 95% CI=1.22-1.88) than participants with no sarcopenia. A restricted cubic spline analysis revealed a J-shaped association between fat mass and all-cause mortality. Further, sarcopenia was also associated with a higher risk of cancer-specific mortality (aHR=1.74, 95% CI=1.23-2.29) compared to non-sarcopenia. The association between sarcopenia and all-cause mortality was twice as strong in Non-Hispanic Blacks (aHR=2.99, 95% CI=1.39-6.06) compared to Non-Hispanic Whites (aHR=1.53, 95% CI=1.19-1.95). Conclusion: Our findings show opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors. Citation Format: Livingstone Aduse-Poku, Shama D. Karanth, Meghann Wheeler, Danting Yang, Caretia Washington, Jesus Fabregas, Ting-Yuan David Cheng, Dejana Braithwaite. Associations of total body fat mass and skeletal muscle index with all-cause and cancer-specific mortality in cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3036.

Survival Comparison of Incidentally Found versus Clinically Detected Thyroid Cancers: An Analysis of a Nationwide Cohort Study.

The true benefit of thyroid cancer screening is incompletely understood. This study investigated the impact of ultrasound screening on thyroid cancer outcomes through a comparison with symptomatic thyroid cancer using data from a nationwide cohort study in Korea. Cox regression analysis was performed to assess the hazard ratios (HRs) for all-cause and thyroid cancer-specific mortality. Considering the possible bias arising from age, sex, year of thyroid cancer registration, and confounding factors for mortality (including smoking/drinking status, diabetes, and hypertension), all analyses were conducted with stabilized inverse probability of treatment weighting (IPTW) according to the route of detection. Of 5,796 patients with thyroid cancer, 4,145 were included and 1,651 were excluded due to insufficient data. In comparison with the screening group, the clinical suspicion group was associated with large tumors (17.2±14.6 mm vs. 10.4±7.9 mm), advanced T stage (3-4) (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), extrathyroidal extension (OR, 1.16; 95% CI, 1.02 to 1.32), and advanced stage (III-IV) (OR, 1.16; 95% CI, 1.00 to 1.35). In IPTW-adjusted Cox regression analysis, the clinical suspicion group had significantly higher risks of all-cause mortality (HR, 1.43; 95% CI, 1.14 to 1.80) and thyroid cancer-specific mortality (HR, 3.07; 95% CI, 1.77 to 5.29). Mediation analysis showed that the presence of thyroid-specific symptoms was directly associated with a higher risk of cancer-specific mortality. Thyroid-specific symptoms also indirectly affected thyroid cancer-specific mortality, mediated by tumor size and advanced clinicopathologic status. Our findings provide important evidence for the survival benefit of early detection of thyroid cancer compared to symptomatic thyroid cancer.

Associations of Total Body Fat Mass and Skeletal Muscle Index with All-Cause and Cancer-Specific Mortality in Cancer Survivors.

Purpose: The importance of body composition on cancer outcomes is of great clinical interest. Measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. We investigated whether the risk of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Our secondary aim was a subgroup analysis assessing the role of race within these associations. Methods: Participants included 1682 adult cancer survivors who had undergone a dual-energy X-ray absorptiometry (DXA) examination to measure body composition, from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was considered as having an appendicular skeletal muscle mass index less than 7.26 kg/m2 for males and less than 5.45 kg/m2 for females. Multivariable Cox proportional hazard models estimated the adjusted hazard ratio (aHR) and 95% confidence interval (CI). Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. The prevalence of sarcopenia was 25.0% (N = 304), and 33.4% (N = 561) had a high total fat mass. Participants with a higher fat mass (aHR = 1.30, 95% CI = 1.06-1.61) and with sarcopenia (aHR = 1.51, 95% CI = 1.22-1.88) had a 30% and 51% increased risk of all-cause mortality compared to participants with a low fat mass and with no sarcopenia, respectively. Further, sarcopenia (aHR = 1.74, 95% CI = 1.23-2.29) was associated with a higher risk of cancer-specific mortality in cancer survivors. The association between sarcopenia and all-cause mortality was twice as strong in Black people (aHR = 2.99, 95% CI = 1.39-6.06) compared to White people (aHR = 1.53, 95% CI = 1.19-1.95). Conclusions: Our findings show the opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and that the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors.

The Clinical Significance of pT3a Lesions as Well as Unilateral Versus Bilateral Invasion Into the Seminal Vesicle in Men With pT3b Prostate Cancer: A Proposal for a New pT3b Subclassification.

Seminal vesicle invasion (SVI) as pT3b prostate cancer generally, but not uniformly, indicates poor prognosis. To determine the clinical impact of pT3a lesions (ie, extraprostatic extension other than seminal vesicle or bladder invasion [EPE], microscopic bladder neck invasion [mBNI]), as well as unilateral (Uni) versus bilateral (Bil) SVI in pT3b disease. We assessed radical prostatectomy findings and long-term oncologic outcomes in 248 consecutive patients with pT3b disease. Focal EPE, nonfocal EPE, mBNI, Uni-SVI, and Bil-SVI were identified in 13 (5.2%), 206 (83.1%), 48 (19.4%), 109 (44.0%), and 139 (56.0%) cases, respectively. Of possible combinations, we eventually divided our cases into 3 cohorts-Group 1: Uni/Bil-SVI and EPE-/mBNI- (n = 28; 11.3%); Group 2: Uni-SVI and EPE or mBNI (n = 103; 41.5%); and Group 3: Bil-SVI and EPE or mBNI (n = 70; 28.2%) or Uni/Bil-SVI and EPE+/mBNI+ (n = 47; 19.0%). Group 3 patients showed significant adverse histopathologic findings, compared with Group 1 or Group 2 patients. Kaplan-Meier analysis revealed that the prognosis was worse in the following order: Group 1, Group 2, and Group 3; and the differences in progression-free survival between any 2 groups were statistically significant. These significant differences were also seen in subgroups, such as those without or with adjuvant therapy before recurrence and those without lymph node metastasis. Additionally, Group 3 patients had a significantly higher risk of cancer-specific mortality than Group 2 patients. In multivariate analysis (Group 2 as a reference), Group 1 (hazard ratio [HR] = 0.169, P = .01) and Group 3 (HR = 1.620, P = .04) showed significance for progression. From these significant findings, we propose a novel pT3b subclassification, namely pT3b1 (Group 1), pT3b2 (Group 2), and pT3b3 (Group 3), which more accurately stratifies its prognosis.

Racial and ethnic differences in type II endometrial cancer mortality outcomes: The contribution of sociodemographic, clinicopathologic, and treatment factors

ObjectiveThe burden of type II endometrial cancer (EC) is rising dramatically in the U.S. Although type II EC disproportionately affects Black women, the magnitude of racial/ethnic differences in type II EC mortality outcomes and factors underlying these differences remain understudied. We examined racial/ethnic differences in cancer-specific and overall mortality in women with type II EC and quantified the extent to which mortality differences are mediated by sociodemographic, clinicopathologic, and treatment factors. Methods14,710 women ≥18 years with type II EC from 2007 to 2016 were identified from the Surveillance, Epidemiology, and End Results database. The association between race/ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic, and non-Hispanic Asian/Pacific Islander [NHAPI]) and cancer-specific and overall mortality was examined. Mediation analysis was used to identify factors underlying differences in mortality outcomes. ResultsNHB women had a higher risk of cancer-specific mortality than NHW women (hazard ratio [HR]: 1.22, 95% CI: 1.12–1.33), whereas NHAPI (HR: 0.88, 95% CI: 0.78–0.99) and Hispanic women (HR: 0.91, 95% CI: 0.81–1.01) had a lower risk of cancer-specific mortality than NHW women. Differences in clinicopathologic (stage, grade, histologic subtype), sociodemographic (insurance type, geographic region and location, neighborhood socioeconomic status), and treatment factors (treatment type, lymphadenectomy) explained 43.5%, 8.1%, and 7.3% of the difference in cancer-specific mortality between NHB and NHW women, respectively. Similar results were noted for overall mortality. ConclusionsMultidisciplinary and multilevel approaches that integrate and address social and biological factors are needed to reduce the disproportionate burden of type II EC mortality in NHB women.

Comparison of Survival Outcomes and Risk Factors Between Ductal Carcinoma of the Prostate and Acinar Adenocarcinoma of the Prostate: A Population-based Propensity Score–matching Study

BackgroundDuctal carcinoma of the prostate (DCP) is a rare type of prostate cancer (PCa) with a higher degree of infiltration and worse prognosis than acinar adenocarcinoma of the prostate (ACP). Previous reports comparing DCP and ACP have not been very reliable and involved small sample sizes. ObjectiveTo assess differences in mortality between ACP and DCP in a large-scale study. Design, setting, and participantsData were downloaded from the Surveillance, Epidemiology, and End Results database in June 2022. Data for 823 939 patients diagnosed with PCa from 2004 to 2019 were examined, excluding cases with survival data missing or pathological types other than DCP and ACP. Outcome measurements and statistical analysisPrognostic and risk factors for DCP were analyzed by generating a propensity score–matched cohort of DCP and ACP cases (1:5). Adjusted Cox models were constructed to determine hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer-specific mortality (CSM) and overall mortality (OM) Results and limitationsA total of 822 607 cases (99.8%) has ACP and 1332 (0.2%) had DCP. In comparison to ACP, age at diagnosis was significantly lower for DCP (≤66 yr: 38.0% vs 50.7%; p < 0.001) and a higher proportion of DCP patients distant metastases (13.7% vs 5.1%; p < 0.001). In comparison to the ACP group, significantly higher proportions of the DCP group underwent surgery (66.1% vs 38.1%; p < 0.001), radiotherapy (13.7% vs 3.1%; p < 0.001), or systemic therapy (18.2% vs 3.3%; p < 0.001). However, the median overall survival time was significantly shorter for DCP patients (44.0 vs 73.0 mo; p < 0.001). DCP patients also had higher risk of CSM (HR 2.07, 95% CI 1.68–2.56; p < 0.001) and OM (HR 2.73 95% CI 2.42–3.08; p < 0.001) after propensity score matching to adjust for the influence of baseline variables. Subgroup analysis showed that DCP patients who had surgical treatment had better CSM than those without surgery, while DCP patients with regional and lower stage had better OM than those with distant stage (both p < 0.05 for interaction). ConclusionsThe risk of CSM and OM is significantly higher for DCP than for ACP. Earlier detection (lower stage) and surgical treatment are beneficial factors for DCP prognosis. Patient summaryWe studied survival rates for two different types of prostate cancer. We found that survival is worse for the rarer ductal carcinoma of the prostate (DCP) than for the more common acinar adenocarcinoma of the prostate. Both early diagnosis when the cancer is at a lower stage and surgical treatment are beneficial for survival in patients with DCP.

Time to second biochemical recurrence as a prognostic indicator in postprostatectomy patients who undergo salvage radiation therapy: An RTOG 9601 based post hoc analysis.

The prognostic significance of a "second" biochemical recurrence (sBCR) after salvage radiation therapy (sRT) with/without hormonal therapy following primary radical prostatectomy in men with prostate cancer has not been examined. We hypothesized that a shorter time to sBCR will be associated with worse cancer control outcomes. The RTOG 9601 study included 760 patients with tumor stage pT2/T3, pN0, who had either persistently elevated prostate-specific antigen (PSA) postradical prostatectomy or developed subsequent biochemical recurrence with PSA levels between 0.2 and 4.0 ng/ml. All patients received sRT (with or without 2 years of Bicalutamide) from 1998 to 2015. For our study, we focused on 421 patients who had sBCR after sRT-which was defined as a PSA increase of at least 0.3 ng/ml over the first nadir. Patients were divided into two categories: early sBCR (n = 210) and late sBCR (n = 211) using median time to sBCR (3.51 years). All patients who experienced sBCR received salvage hormonal therapy. Competing-risk analysis was used to examine the impact of early versus late sBCR on prostate cancer specific mortality (CSM), after accounting for available covariates. The majority of patients were age 60 years or older (75.8%), had pT3 disease (74.8%), and Gleason score 7 (75.2%). Overall, 13.8% had persistent PSA initially after surgery. At 10 years, starting at the time of sBCR, CSM rate was 31.3% in the early sBCR group versus 20.0% in the late sBCR group. In competing-risk analysis, time to sBCR was an independent predictor of CSM, where patients with early sBCR had 1.7-fold higher CSM risk (p = 0.026) than their counterparts with late sBCR. Time to sBCR after sRT (with or without concomitant Bicalutamide) is a significant predictor of CSM following initial radical prostatectomy. This information can be used to guide subsequent treatments, and to counsel patients.

The effect of race/ethnicity on cancer-specific mortality after salvage radical prostatectomy.

BackgroundTo test the effect of race/ethnicity on cancer-specific mortality (CSM) after salvage radical prostatectomy (SRP).Material and methodsWe relied on the Surveillance, Epidemiology and End Results database (SEER, 2004–2016) to identify SRP patients of all race/ethnicity background. Univariate and multivariate Cox regression models addressed CSM according to race/ethnicity.ResultsOf 426 assessable SRP patients, Caucasians accounted for 299 (69.9%) vs. 68 (15.9%) African-Americans vs. 39 (9.1%) Hispanics vs. 20 (4.7%) Asians. At diagnosis, African-Americans (64 years) were younger than Caucasians (66 years), but not younger than Hispanics (66 years) and Asians (67 years). PSA at diagnosis was significantly higher in African-Americans (13.2 ng/ml), Hispanics (13.0 ng/ml), and Asians (12.2 ng/ml) than in Caucasians (7.8 ng/ml, p = 0.01). Moreover, the distribution of African-Americans (10.3%–36.6%) and Hispanics (0%–15.8%) varied according to SEER region. The 10-year CSM was 46.5% in African-Americans vs. 22.4% in Caucasians vs. 15.4% in Hispanics vs. 15.0% in Asians. After multivariate adjustment (for age, clinical T stage, lymph node dissection status), African-American race/ethnicity was an independent predictor of higher CSM (HR: 2.2, p < 0.01), but not Hispanic or Asian race/ethnicity. The independent effect of African-American race/ethnicity did not persist after further adjustment for PSA.ConclusionAfrican-Americans treated with SRP are at higher risk of CSM than other racial/ethnic groups and also exhibited the highest baseline PSA. The independent effect of African-American race/ethnicity on higher CSM no longer applies after PSA adjustment since higher PSA represents a distinguishing feature in African-American patients.

The Cancer of the Bladder Risk Assessment (COBRA) score accurately predicts cancer-specific survival after radical cystectomy: external validation and lymphovascular invasion assessment value to improve its performance.

The Cancer of the Bladder Risk Assessment (COBRA) score is a predictive tool for estimating Cancer Specific Survival (CSS) after Radical Cystectomy (RC) for urothelial carcinoma. COBRA score variables are: age at RC, Tumor stage and Lymph Node Density (LND). We sought to externally validate the COBRA score and to improve its performance in estimating CSS adding Lymphovascular Invasion (LVI) as a further variable (Modified COBRA score). Clinicopathological and survival data from 789 patients who underwent RC and Pelvic Lymph Node Dissection (PLND) between January 2007 and December 2020 in two European referral centers (Paris, France and Badalona, Spain) were analyzed. COBRA score was applied to our cohort and CSS Kaplan-Meier curves were performed. Univariable and Multivariable analysis was performed in order to identify risk factors for Cancer Specific Mortality (CSM) and a score was assigned for any statistically significant risk factor; afterward, c-index calculation was performed and CCS curves have been plotted for the model after having integrated LVI variable to the COBRA score. Finally, we compared both COBRA score and Modified COBRA score models with the established AJCC model. A total of 789 patients underwent RC during the observation period. Complete data were available for 731 patients with a median follow-up of 32 months (8-47). CSM was 27.6% (no. 218 patients) at follow-up. When COBRA score was applied to our cohort, c-index was 0.76. Regression COX analysis has shown HR 0.36, CI 95% (0.16-0.83), P=.016 for patients with COBRA score 1; HR 0, CI 95% (0-1.77), P =.94 for score 2; HR 0.51, CI 95% (0.39 -0.67), P =.001 for score 3; HR 1.67, CI 95% (1.23-2.27), P =.001 for score 4; HR 2.45, CI 95% (1.51-3.99), P =.001 for score 5; HR 2.01, CI 95% (1.42-2.85), P =.001 for score 6 and HR 0.66, CI 95% (0.09-4.73), P =.682 for score 7. When the LVI variable was added to the CSS predictive model the discriminatory power increased to a c-index of 0.78. COBRA score adequately identifies those patients with a higher risk of CSM, with a c-index of 0.76. Moreover, LVI variable further improves its predictive accuracy from c-index of 0.76 to c-index of 0.78. LVI variable could be integrated in the COBRA score to optimizing prognosis stratification for patients who undergo RC.

The association between NOTCH3 expression and the clinical outcome in the urothelial bladder cancer patients.

Disrupted NOTCH activity is a driving event in urothelial bladder cancer (UBC). After activation by hypoxia, the NOTCH3 receptor participates in tumor cell proliferation, acquisition of the epithelial-mesenchymal transition phenotype, and angiogenesis. The aim was to analyze the association of NOTCH3 expression with histopathological and clinical parameters and to determine its predictive impact on the clinical outcome in UBC patients. The present research included 614 UBC samples incorporated in paraffin tissue microarrays, evaluated by immunohistochemistry for NOTCH3 expression. The accrual period was 4 years, while the follow-up period was 2 years. The membranous expression was semi-quantified (0-3), and the mean degree was 1.81 ± 0.94. Criteria for semi-quantification, the NOTCH3 expression, were the intensity of the staining and the percentage of positive cells. The samples with negative (0) and weak (1) NOTCH3 immunohistochemical (IHC) score were considered negative, while the samples that showed moderate (2) and strong (3) expression were considered positive. Higher degree of positivity was associated with higher risk of cancer-specific mortality (p < 0.001). Independent predictors for cancer-specific mortality were NOTCH3 expression and high stage (p < 0.001). NOTCH3 expression was not a statistically significant predictor of recurrence-free survival (p = 0.816). This study indicated that NOTCH3 is a predictor of poor outcome, suggesting that the NOTCH3 could be potentially reliable IHC marker for selecting the UBC patients that would require more intensive follow-up, especially if they diagnosed in higher stage, with divergent differentiation in pathological report, and without recurrences which would lead them to more frequent medical assessments.

PD-L1 Expression and Clinicopathological Factors in Renal Cell Carcinoma: A Comparison of Antibody Clone 73-10 With Clone 28-8

Expression of programmed death ligand-1 (PD-L1) is associated with poor prognosis in renal cell carcinoma (RCC). Although a new antibody clone for immunohistochemical assay, 73-10, has shown greater sensitivity than other assays (28-8, 22C3, SP142, and SP263) in non-small cell lung cancer, PD-L1 expression using 73-10 has never been assessed in RCC. Therefore, this study aimed to evaluate the association of clinicopathological factors with PD-L1 expression detected by clone 73-10 and compare it with that detected by 28-8. Tissue microarray samples from 582 patients who underwent radical or partial nephrectomy for RCC were immunohistochemically assessed using clones 73-10 and 28-8. The positivity for PD-L1 expression in RCC by 73-10 was higher than that of 28-8 and significantly associated with worse pathological factors and a higher risk of cancer-specific mortality. Positivity for PD-L1 expression by 73-10, as compared to 28-8, was associated with worse clinicopathological factors and prognosis for patients with RCC.

Higher Cancer Mortality in Rural Upper Urinary Tract Urothelial Carcinoma Patients

Objective: The aim of the study was to investigate differences in the stage at presentation and cancer-specific mortality (CSM) between rural area (RA) and urban area (UA) residence status in nonmetastatic upper urinary tract urothelial carcinoma (UTUC) patients. Methods: Newly diagnosed T_1–3N₀M₀ UTUC patients with available residence status were abstracted from the Surveillance, Epidemiology, and End Results database (2004–2016). Propensity score (PS) matching (1 RA vs. 3 UA) accounted for age (interval ≤2 years), T stage (exact matching: T1, T2, and T3), and tumor grade (exact matching: high grade, low grade/unknown). Cumulative incidence plots and multivariable competing risk regression models focused on CSM, after adjustment for other-cause mortality. Results: Of 6,012 patients, 125 (2.1%) resided in RAs and 5,887 (97.9%) in UAs. RA patients were younger than UA patients (median age 72 vs. 75 years, p = 0.03). No differences were recorded in tumor location, T stage, tumor grade, or surgical treatment between RA and UA patients. After 1:3 PS matching, 125 RA patients and 375 UA patients were assessable. At 5 years of follow-up, CSM rates were 26.7 versus 15.7% according to RA versus UA, respectively. After additional multivariable adjustment for age, sex, tumor location, and surgical treatment, RA remained an independent predictor of higher CSM (hazard ratio 1.75, p = 0.02). Conclusions: Despite no differences in cancer characteristics, UTUC patients in RA are at higher risk of CSM than their UA counterparts. This suggests suboptimal care delivery and compliance as possible causes. Complex and/or rare disease should be centralized to expert centers, which are often in UAs.

Racial and socioeconomic disparities in retroperitoneal lymph node dissection and survival in nonseminomatous germ cell tumor: A population-based study

BackgroundThough testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs). MethodsWithin the Surveillance Epidemiology and End Results database (2005–2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality. ResultsPatients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40–0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15–1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46–0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27–0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12–6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48–16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively. ConclusionsThis national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival.

Association of Allostatic Load with All-Cause andCancer Mortality by Race and Body Mass Index in theREGARDS Cohort.

Among 29,701 Black and White participants aged 45 years and older in the Reasons for Geographic and Racial Difference in Stroke (REGARDS) study, allostatic load (AL) was defined as the sum score of established baseline risk-associated biomarkers for which participants exceeded a set cutoff point. Cox proportional hazard regression was utilized to determine the association of AL score with all-cause and cancer-specific mortality, with analyses stratified by body-mass index, age group, and race. At baseline, Blacks had a higher AL score compared with Whites (Black mean AL score: 2.42, SD: 1.50; White mean AL score: 1.99, SD: 1.39; p < 0.001). Over the follow-up period, there were 4622 all-cause and 1237 cancer-specific deaths observed. Every unit increase in baseline AL score was associated with a 24% higher risk of all-cause (HR: 1.24, 95% CI: 1.22, 1.27) and a 7% higher risk of cancer-specific mortality (HR: 1.07, 95% CI: 1.03, 1.12). The association of AL with overall- and cancer-specific mortality was similar among Blacks and Whites and across age-groups, however the risk of cancer-specific mortality was higher among normal BMI than overweight or obese participants. In conclusion, a higher baseline AL score was associated with increased risk of all-cause and cancer-specific mortality among both Black and White participants. Targeted interventions to patient groups with higher AL scores, regardless of race, may be beneficial as a strategy to reduce all-cause and cancer-specific mortality.

Signet-Ring Cell Carcinoma as an Independent Prognostic Factor for Patients With Urinary Bladder Cancer: A Population-Based Study

Background: Primary signet-ring cell carcinoma (SRCC) is a rare variation of adenocarcinoma. Although SRCC of the urinary bladder is highly malignant, it is often neglected due to its rarity.Materials and Methods: We used the national Surveillance, Epidemiology, and End Results (SEER) database (2004–2016) to compare SRCC with urothelial carcinoma (UC) and investigated the prognostic values of the clinicopathological characteristics and survival outcomes in SRCC of the urinary bladder. Multivariable Cox proportional hazard model, subgroup analyses, and propensity score matching (PSM) were used.Results: In all, 318 patients with SRCC and 57,444 patients with UC were enrolled. Compared with those with UC, patients with SRCC were younger at diagnosis (P < 0.001) and had higher rates of muscle invasive disease (P < 0.001), lymph node metastasis (P < 0.001), and distal metastasis (P < 0.001), as well as higher-grade tumors (P = 0.004). A Cox proportional hazard regression analysis showed that the SRCC group was associated with significantly higher risks of overall mortality (OM) compared with the UC group [hazard ratios (HR) = 1.44, 95% confidence intervals (95% CI) = 1.26–1.63, P < 0.0001]. Patients with SRCC also had a higher risk of cancer-specific mortality (CSM; HR = 1.40, 95% CI = 1.18–1.65, P < 0.0001). After PSM, the SRCC group also experienced higher risks of OM (HR = 1.45, 95% CI = 1.24–1.68, P < 0.0001) and CSM (HR = 1.47, 95% CI = 1.20–1.79, P = 0.0001) compared with the UC group. In the subgroup analyses, no significant interactions were observed in sex, age, N stage, M stage, and lymph nodes removed in terms of both OM and CSM.Conclusion: The prognosis of SRCC is poorer than that of UC, even after adjustment for baseline demographic and clinicopathological characteristic as well as cancer treatment. SRCC is an independent prognostic factor for patients with urinary bladder cancer.

Some ways of improvement of detection of hormone-naive non-metastatic high-risk prostate cancer

Purpose: To confirm additional criteria (not including standard Tumor-Node-Metastasis (TNM) classification, prostate specific antigen (PSA) and Gleasson score) to improve stratification of hormone-naпve non-metastatic high-risk prostate cancer. Materials and methods: Detailed literature analysis with utilization of Pubmed data had been performed, and additional approaches to standard classification had been found. Conclusions: – specific criteria of high-risk prostate cancer periodically change in appropriate guidelines and clinical researches, according to different prospects in “risk” detection between different experts in oncourology and radiation oncology; – except modern classification, new data obtained concerning measurement of the tumor size can provide additional diagnostic value; – more clear visualization, exactly, multiparametric magnetic resonance imaging, can also provide appropriate information about stage and size of the tumor and, thereby, helps to identify high-risk prostate cancer; – specified definition of non-metastatic high-risk prostate cancer had been confirmed; – in high risk group patients with multiple criteria of specified condition have higher risk of cancer-specific mortality.