Higher Cancer-specific Mortality Research Articles

Second Primary Malignancies in Patients with Colorectal Cancer: A Population-Based Analysis.

PurposeThis study aimed to profile the characteristics of patients with colorectal cancer (CRC) with a second primary malignancy (SPM) and to identify patients with CRC at high risk of developing SPMs.MethodsWe retrospectively reviewed data on patients with CRC aged 20–79 years from the Surveillance, Epidemiology, and End Results (SEER) database. Eligible patients were categorized into only one primary malignancy and SPM cohorts. A competing‐risk model was used to quantify associations between SPM occurrence and the multiple traits of patients. Finally, a decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model by calculating net benefit.ResultsA total of 179,884 patients were identified, 18,285 (10.2%) of whom developed SPMs during a maximum follow‐up of approximately 18 years. The median survival time after the second diagnosis was less than 4 years. The 3‐year, 5‐year, and 10‐year cumulative risks of developing an SPM were 3.9%, 5.9%, and 10.0%, respectively. According to the multivariable competing‐risk model, male colon cancer survivors, older in age, with a well‐differentiated tumor and localized disease, who were treated with surgery were susceptible to SPMs. The DCA yielded a wide range of risk thresholds at which the net benefits would be obtained from our proposed model.ConclusionCRC survivors remain at high risk of developing SPMs. Patients with a second diagnosis of cancer showed not only significantly worse survival but also higher cancer‐specific mortality. A web‐based individualized predictive tool was also provided to assist clinicians in identifying patients at high risk of developing SPMs and planning their future care management.Implications for PracticeColorectal cancer survivors remain at high risk of developing a second primary malignancy (SPM). This study aimed to profile the characteristics of patients with colorectal cancer with second primary malignancies and to further explore the risk factors related to the development of second primary malignancies, using a large population‐based cohort. A clinically useful competing‐risk nomogram was developed to predict the risk of SPMs based on individual clinical factors. According to the findings, older age, male sex, white or black race, localized disease, and treatment with surgery among patients with colon cancer were associated with an increased risk of developing an SPM. These findings and the proposed tool could be useful to clinicians and caregivers in the clinical counseling of patients with colorectal cancer and the development of long‐term care management.

Depression and anxiety in relation to cancer incidence and mortality: a systematic review and meta-analysis of cohort studies.

The link between depression and anxiety status and cancer outcomes has been well-documented but remains unclear. We comprehensively quantified the association between depression and anxiety defined by symptom scales or clinical diagnosis and the risk of cancer incidence, cancer-specific mortality, and all-cause mortality in cancer patients. Pooled estimates of the relative risks (RRs) for cancer incidence and mortality were performed in a meta-analysis by random effects or fixed effects models as appropriate. Associations were tested in subgroups stratified by different study and participant characteristics. Fifty-one eligible cohort studies involving 2,611,907 participants with a mean follow-up period of 10.3 years were identified. Overall, depression and anxiety were associated with a significantly increased risk of cancer incidence (adjusted RR: 1.13, 95% CI: 1.06-1.19), cancer-specific mortality (1.21, 1.16-1.26), and all-cause mortality in cancer patients (1.24, 1.13-1.35). The estimated absolute risk increases (ARIs) associated with depression and anxiety were 34.3 events/100,000 person years (15.8-50.2) for cancer incidence and 28.2 events/100,000 person years (21.5-34.9) for cancer-specific mortality. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety were related to higher cancer incidence, poorer cancer survival, and higher cancer-specific mortality. Psychological distress (symptoms of depression and anxiety) was related to higher cancer-specific mortality and poorer cancer survival but not to increased cancer incidence. Site-specific analyses indicated that overall, depression and anxiety were associated with an increased incidence risks for cancers of the lung, oral cavity, prostate and skin, a higher cancer-specific mortality risk for cancers of the lung, bladder, breast, colorectum, hematopoietic system, kidney and prostate, and an increased all-cause mortality risk in lung cancer patients. These analyses suggest that depression and anxiety may have an etiologic role and prognostic impact on cancer, although there is potential reverse causality; Furthermore, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. Early detection and effective intervention of depression and anxiety in cancer patients and the general population have public health and clinical importance.

Evaluation of individual and cumulative sites of extrarenal tumor invasion in pT3a clear cell renal cell carcinoma

IntroductionThe Tumor-Node-Metastasis classification of renal cell carcinoma (RCC) for pT3a tumors includes sinus fat invasion (SFI), perinephric fat invasion (PFI), renal vein invasion (RVI), and/or pelvicaliceal system invasion (PSI). The purpose of this study was to determine the association between these patterns of invasion (assessed individually and cumulatively) with the development of metastases and cancer-specific mortality (CSM). Materials and methodsWe identified 160 patients who underwent radical nephrectomy for pT3a clear cell RCC between 2011 and 2017. The association between individual patterns of invasion and metastases and cancer-specific survival were evaluated with multivariate logistic regression. Cox Hazard proportion ratios and Kaplan-Meier survival curves were generated for patterns of invasion (assessed individually and cumulatively). ResultsThe number of individual invasive patterns was as follows: 97/160 (61%) presented with RVI, 91/160 with SFI (57%), 62/160 with PFI (39%), and 24/160 (15%) with PSI. At multivariate analysis, both PFI and RVI were associated with metastases (P < 0.001 and 0.028, respectively). PFI (hazard ratio [HR] 4.12, 95% confidence interval [CI] 2.14–7.92; P < 0.001), RVI (HR 2.44, 95% CI 1.18–5.01; P = 0.015), SFI (HR 2.13, 95% CI 1.05–4.34; P = 0.036) had higher CSM, while PSI (HR 1.43, 95% CI 0.65-3.16; p = 0.38) did not show increased CSM. Furthermore, cumulative analysis showed that multiple invasive patterns resulted in worse CSM (p < 0.001). ConclusionsIn our study, PFI was associated with the most aggressive behavior while PSI was the most indolent. Furthermore, the presence of more than one pattern of invasion was associated with worse CSM. These results indicate that reporting of the individual location and cumulative amount of pT3a patterns of invasion in clear cell RCC is clinically relevant.

213P - An observational retrospective real-world study of sarcomatoid renal cell carcinoma (sRCC) patients in an Asian cancer centre

BackgroundRenal cell carcinoma with sarcomatoid de-differentiation (sRCC) is a highly aggressive form RCC with trials reporting a poor median OS of 5 to 12 months. Recent genomics profiling of sRCC suggest that Srcc is not a single entity but is highly influenced by the parent RCC subtype from which its shares histological characteristic. A recent meta-analysis suggests that sRCC is associated with a higher cancer specific mortality, poorer progression free and overall survival but not gender and average age. A population-based study of 879 patients taken from the SEER data showed that the 5-year DSS were 77.7%, 67.8%, 35.4%, and 3.5% for patients with stage I, II, III, and IV disease at diagnosis. MethodsA retrospective analysis was conducted on patients diagnosed with sRCC from 1997 to 2018. Disease characteristics, treatment outcomes and adverse events were retrieved from digital medical records. Overall survival and progression free survival were estimated using Kaplan Meier method. Results62 patients with a diagnosis of sRCC were identified. 72% (n = 45) were males. Median age was 56 years old on diagnosis. Majority of patients were Chinese at 72%. 52%(N = 32) were metastatic on diagnosis with 18%(n = 12) were diagnosed with initially early stages(I-II). 80%(n = 47) were symptomatic from the cancer on diagnosis with at least 1 symptom of haematuria, flank pain, fever, loss of weight. Majority of the patients (n = 54) had were clear cell rcc with sarcomatoid component while the 7% (n = 5) were papillary rcc. The median overall survival for the metastatic group was 1.26 years with 53% having had VEGF inhibitors as first line treatment while about a quarter had no treatment. ConclusionsWe currently report the disease characteristics and treatment of patients diagnosed with sRCC in our tertiary cancer centre. In our study, about half of the cohort was metastatic on diagnosis with another 20% having early stage on initial diagnosis. The overall survival outcomes of this real world metastatic sRCC group is promising and appears better than prior reports. More research is needed to better understand this group of patients with poor outcomes. Legal entity responsible for the studyRavindran Kanesvaran. FundingHas not received any funding. DisclosureR. Kanesvaran: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Johnson and Johnson. All other authors have declared no conflicts of interest.

Impact of age on stage-specific mortality in patients with gastric cancer: A long-term prospective cohort study.

Controversies exist regarding the impact of age on gastric cancer-related mortality according to cancer stage. In our prospective cohort study, we evaluated the impact of age on stage-specific mortality in patients with gastric cancer. Between 2002 and 2006, patients with newly diagnosed gastric cancer were recruited from two university-affiliated hospitals in Korea. Follow-up data were updated regularly based on medical records and telephone surveys. Patients were classified into four subgroups according to age: <50, 50–59, 60–69, and 70–79 years. A total of 448 patients were followed up for 81.6 months (interquartile range, 25.0–139.3 months). The number of patients with stage I, II, III, and IV disease was 247, 74, 88, and 39, respectively. Overall, age was an independent risk factor for gastric cancer-specific mortality (hazard ratio [HR], [95% confidence interval (CI)]: 1.53 [0.91–2.57], 1.88 [1.21–2.91], and 2.64 [1.69–4.14] in the 50–59, 60–69, and 70–79 years groups, respectively, with the <50 years group as reference). In patients with stage I and II gastric cancer, the 70–79 years group was associated with a significantly higher rate of cancer-specific mortality than the <50 years group (stage I: HR [95% CI], 9.55 [2.11–43.12]; stage II: HR [95% CI], 7.17 [2.32–22.18]). However, age was not an independently associated factor for cancer-specific mortality in patients with stage III and IV gastric cancer. Although age was an independent risk factor for gastric cancer-related mortality in patients with gastric cancer, its impact may differ depending on the stage of cancer.

Epidemiologic perspectives on immunosuppressed populations and the immunosurveillance and immunocontainment of cancer.

The advent in the last several years of effective immunotherapy for cancer has renewed interest in the role of the immune system in controlling cancer. The idea that the immune system can help control cancer has a long history. Solid organ transplant recipients (SOTRs) as well as human immunodeficiency virus (HIV)-infected people are affected by cell-mediated immune dysfunction. Epidemiologic studies of these populations reveal a pattern characterized by a strongly increased incidence of virus-related cancers (eg, Kaposi sarcoma, non-Hodgkin lymphoma, and anogenital cancers). In addition, recent epidemiologic studies have evaluated cancer-specific mortality among SOTRs and HIV-infected people following a cancer diagnosis. For a wider range of cancers-not limited to those caused by viruses, and including melanoma and cancers of the colorectum, lung, and breast- these immunosuppressed cancer patients have higher cancer-specific mortality than other cancer patients. This latter group of cancers somewhat mirrors those for which immunotherapy with checkpoint inhibitors is approved. These epidemiologic observations suggest that there are 2 distinct immune selection processes in humans: immunosurveillance directed against premalignant cells before cancer diagnosis (most relevant for preventing virus-related cancers), and "immunocontainment" directed against established cancers. These processes thus appear relevant for different groups of malignancies and may have different mechanisms.

The impact of race and socioeconomic status on outcomes for HPV-associated squamous cell carcinoma of the head and neck.

e18103 Background: The socioeconomic factors affecting outcomes of human papillomavirus (HPV)-associated squamous cell carcinoma of the head and neck (SCCHN) are poorly characterized. Methods: A custom Surveillance, Epidemiology, and End Results (SEER) database identified adult patients with primary non-metastatic SCCHN and known HPV status diagnosed between 2013-14. Multivariable logistic regression defined associations between patient characteristics and HPV status, with adjusted odds ratios (AORs) and 95% confidence intervals (CIs) reported. Fine-Gray competing risks regression estimated adjusted hazard ratios (AHRs) and 95% CIs for cancer-specific mortality (CSM), including a disease subsite*HPV status*race interaction term. Results: 4735 patients with non-metastatic SCCHN and known HPV status were identified. HPV-associated SCCHN was positively associated with oropharyngeal primary, male sex and higher education and negatively associated with uninsured status, single marital status, and non-white race (p≤0.001 for all). For HPV-positive oropharyngeal SCCHN, white race was associated with lower CSM (AHR 0.55, 95%CI 0.34-0.88, p = 0.01) and uninsured status was associated with higher CSM (AHR 3.12, 95%CI 1.19-8.13, p = 0.02). These associations were not observed in HPV-negative or non-oropharynx SCCHN. Accordingly, there was a statistically significant disease subsite*HPV status*race interaction (pint&lt; 0.001). Conclusions: Non-white race and uninsured status were associated with worse CSM in HPV-positive oropharyngeal SCCHN, while no such associations were observed in HPV-negative or non-oropharyngeal SCCHN. These results suggest that, despite having clinically favorable disease, non-white patients with HPV-positive oropharyngeal SCCHN have worse outcomes than their white peers. Further work is needed to understand and reduce socioeconomic disparities in SCCHN.

BioScore (B7-H1, survivin, and Ki-67) does not predict cancer-specific mortality in surgically treated patients with renal cell carcinoma: An external validation study

BackgroundTo externally validate‚ BioScore’, a biomarker-based scoring system using immunohistochemical tumor expression levels of B7-H1, survivin, and Ki-67, in a single-center cohort of renal cell carcinoma (RCC) patients. Additionally, we investigated the potential benefit of BioScore as compared to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score. Materials and MethodsThe validation cohort comprised 393 nonmetastatic RCC patients treated with radical nephrectomy or nephron-sparing surgery from 1999 to 2004. Kaplan-Meier estimators, the log-rank test, uni- and multivariable Cox regression models, and measures of discrimination were used to quantify the prognostic performance of BioScore regarding cancer-specific mortality (CSM). ResultsDuring a median follow-up of 7.8 years, 69/132 (52%) deaths were adjudicated to progressive disease. BioScore was weakly associated with CSM in univariable analysis (hazard ratio per 1 point increase = 1.12, 95% confidence interval = 1.02–1.23, P = 0.023). However, this association did not prevail after adjusting for other adverse prognostic factors as represented by the SSIGN score. The discriminative performance of BioScore was very modest (Harrell's C-Index = 0.60) and did not improve the SSIGN score (P = 0.341), which already showed an excellent discrimination, as evidenced by Harrell's C-Index of 0.81. In a sensitivity analysis regarding clear cell RCC patients only, B7-H1 positivity did not emerge as a statistically significant predictor of CSM. ConclusionAlthough a higher BioScore was significantly associated with a higher CSM, the magnitude of this association was weak and not independent from other prognosticators. Moreover, BioScore did not improve the prognostic accuracy of the SSIGN score.

Insulin Resistance and Cancer-Specific and All-Cause Mortality in Postmenopausal Women: The Women's Health Initiative.

Insulin resistance has been proposed as a mediator of the increased cancer incidence and mortality associated with obesity. However, prior studies included limited cancer deaths and had inconsistent findings. Therefore, we evaluated insulin resistance and cancer-specific and all-cause mortality in postmenopausal women participating in the Women's Health Initiative (WHI). Eligible were a subsample of 22837 WHI participants aged 50-79 years enrolled at 40 US clinical centers from 1993 to 1998 who had baseline fasting glucose and insulin levels. Baseline insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Cancers were verified by central medical record review and deaths verified by medical record and death certificate review enhanced by National Death Index queries. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality. All statistical tests were two-sided. During a median of 18.9 years of follow-up, 1820 cancer deaths and 7415 total deaths occurred. Higher HOMA-IR quartile was associated with higher cancer-specific mortality (Q4 vs Q1, HR = 1.26, 95% CI = 1.09 to 1.47; Ptrend = .003) and all-cause mortality (Q4 vs Q1, HR = 1.63, 95% CI = 1.51 to 1.76; Ptrend < .001). A sensitivity analysis for diabetes status did not change findings. Among women with body mass index less than 25 kg/m2, higher HOMA-IR quartile was associated with higher cancer mortality (Fine and Gray, P = .004). High insulin resistance, as measured by HOMA-IR, identifies postmenopausal women at higher risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention.

Which treatment is best for patients with AJCC stage IV bladder cancer?

We sought to identify the method that could obtain the best survival rate for AJCC stage IV bladder cancer (BCa) patients. Patients with AJCC stage IV BCa diagnosed between 2004 and 2015 were identified using the Surveillance, epidemiology and end results (SEER) database. Kaplan-Meier curves and log-rank test were used for overall survival (OS) and cancer-specific survival (CSS). Multivariable Cox regression was used to determine factors associated with all-cause mortality (ACM) and cancer-specific mortality (CSM). We found that among the 11824 patients, the number of patients who received chemotherapy (CT), radiotherapy (RT) and radical cystectomy (RC) was 6243 (52.8%), 2005 (17.0%) and 4987 (42.2%), respectively. Patients who received CT or RC had improved OS (26.4% vs. 11.7%, p < 0.001 and 27.3% vs. 13.7%, p < 0.001, respectively), but patients who underwent RT alone had lower OS (14.4% vs. 20.5%, p < 0.001). Furthermore, CT combined with RC was associated with the lowest ACM (hazard ratio (HR) = 0.26, 95% CI 0.24-0.28, p < 0.001) and the lowest CSM (HR = 0.24, 95% CI 0.22-0.26, p < 0.001). Patients who only received RT had the highest ACM (HR = 0.84, 95% CI 0.77-0.92, p < 0.001) and the highest CSM (HR = 0.85, 95% CI 0.77-0.94, p = 0.002). We concluded that CT combined with RC was the best method with the highest survival rate for patients with AJCC stage IV BCa and that CT combined with RC had more benefits in improving OS and CSS than did RT alone.

Aristolochic acid containing herbs induce gender-related oncological differences in upper tract urothelial carcinoma patients.

BackgroundIn China, upper tract urothelial carcinoma (UTUC) is less prevalent but more malignant in males. This study investigates the prognostic factors and causes of gender-based differences in Chinese populations.MethodsBetween 1999 and 2011, 687 UTUC patients who underwent surgery were utilized for this study. We evaluated the differences in oncological characteristics, epigenetic biomarkers, cancer-specific survival (CSS), bladder recurrence (BR) rate, and contralateral upper tract recurrence (CUTR) rate. Smoking history, benzene exposure history, and the history of using aristolochic acid (AA) containing herbs were analyzed in detail.ResultsCompared with male patients, female patients showed poorer renal function, lower proportions of tumor stage III/IV, and smaller tumor diameters. The CSS in male patients was lower than that in female patients. Significant gender-related differences were observed concerning various prognostic factors. In female patients, poorer survival rates were attributed to the primary tumor location in the ureter, large diameter primary tumors, severe chronic kidney disease, papillary tumor architecture, high tumor stages, positive N status, and methylated ABCC6 promoters. In male patients, older age, ipsilateral hydronephrosis, large tumor diameters, sessile tumor architecture, high tumor stages, and methylated TMEFF2 promoters were associated with higher cancer-specific mortality. AA might be the main cause of these gender-based differences. The AA-induced UTUC patients presented smaller tumor diameters, lower tumor stages, fewer positive N statuses, more multifocal tumors, lower methylation indices, and poorer renal function. Although AA-induced UTUC patients exhibited better survival rates, BR and CUTR rates were significantly worse.ConclusionIn China, there exist significant AA-induced differences between male and female UTUC patients. The bladders and contralateral upper urinary tracts of AA-induced UTUC patients should be carefully monitored after surgery.

The role of perineural invasion in penile cancer: a meta-analysis and systematic review.

The significance of perineural invasion (PNI) present in penile cancer (PC) is controversial. In order to clarify the predictive role of PNI in the inguinal lymph node (ILN) metastases (ILNM) and oncologic outcome of patients, we performed this meta-analysis and systematic review. The search of PubMed, Embase, and Web of Science was conducted for appropriate studies, up to 20 January 2018. The pooled odds ratio (OR) and hazard ratio (HR) with their 95% confidence interval (CI) were applied to evaluate the difference in ILNM and oncologic outcome between patients present with PNI and those who were absent. A total of 298 in 1001 patients present with PNI were identified in current meta-analysis and systematic review. Significant difference was observed in ILNM between PNI present and absent from patients with PC (OR = 2.98, 95% CI = 2.00–4.45). Patients present with PNI had a worse cancer-specific survival (CSS) (HR = 3.58, 95% CI = 1.70–7.55) and a higher cancer-specific mortality (CSM) (HR = 2.20, 95% CI = 1.06–3.82) than those cases without PNI. This meta-analysis and systematic review demonstrated the predictive role of PNI in ILNM, CSS, and CSM for PC patients.

The effect of race on survival after local therapy in metastatic prostate cancer patients.

Local therapy (LT) may offer a survival advantage in highly select, newly diagnosed metastatic prostate cancer (mPCa) patients. However, it is unknown whether the benefits vary in Caucasian vs. African American (AA) patients. Within the Surveillance Epidemiology and End Results (SEER) database (2004-2014), we focused on Caucasians and AA patients with newly diagnosed mPCa treated with LT: radical prostatectomy (RP) and brachytherapy (RT). Endpoints consisted of cancer-specific mortality (CSM) and overall mortality (OM). Kaplan-Meier analyses and multivariable Cox regression models tested for racial difference in CSM and OM. Between 2004 and 2014, we identified 408 (77.2%) Caucasians and 121 (22.8%) AAs with newly diagnosed mPCa treated with LT: RP (n=357) or RT (n=172). According to race, when LT is defined as RP, Caucasian patients had a significantly longer survival vs. AA patients: CSM-free survival 123 vs. 63 months (p=0.004) and OM-free survival 108 vs. 46 months (p=0.002). The CSM and OM benefits were confirmed in multivariable analyses (hazard ratio [HR] 0.56, p=0.01 for CSM; HR 0.60, p=0.01 for OM). However, no differences in CSM or OM were recorded according to race when LT consisted of RT. Our results indicate that race is not associated with difference in survival after LT in mPCa patients. However, when focusing on RP-treated patients, Caucasian race is associated with higher CSM and OM rates relative to AA race. This racial difference does not apply to RT. Our findings should be considered in future prospective trials for the purpose of preplanned stratification according to race.

Rates of Positive Surgical Margins and Their Effect on Cancer-specific Mortality at Radical Prostatectomy for Patients With Clinically Localized Prostate Cancer.

The objective of this study was to investigate positive surgical margin (PSM) rates in patients with prostate cancer treated with radical prostatectomy (RP) and assess PSM impact on cancer-specific mortality (CSM). Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015), we identified men who underwent RP with pathologic T2 or T3a stage. Annual trends of PSM rates were plotted. Subgroups focused on geographic regions, namely the North Central, Northeast, South, and West. Cumulative incidence plots depicted other-cause mortality-adjusted CSM rates. Multivariable competing risks regression models tested the relationship between PSM and CSM. Subgroup analyses focused on pathologic stage, Gleason score, and geographic region. Of 153,329 patients treated with RP, 12.3% (n= 18,935) exhibited PSM. Overall, in pathologic T2 stage and pathologic T3a stage, PSM rates decreased during the study period from 18.7% to 9.7% (P<.001), 15.7% to 7.3% (P< .001), and 39.0% to 18.0% (P< .001), respectively. In subgroup analyses focusing on geographic regions, PSM rates universally decreased. However, the magnitude differed. In multivariable competing risks regression models, PSM rates were associated with higher CSM (hazard ratio, 1.45; P< .001). However, geographic regions failed to reach independent predictor status. Insufficient information about PSM focality, length, and associated Gleason score represent important limitations. It is encouraging that PSM rates decreased during the study period, even after stratification according to tumor stage. PSM decreased within the 4examined geographic regions. However, the rate of decrease varied in magnitude, but geographic regions did not represent an independent predictor of PSM.

Survival outcomes of locally advanced prostate cancer in patients aged < 50years after local therapy in the contemporary US population.

To assess survival outcomes of locally advanced prostate cancer (LAPC) in patients aged < 50years after local therapy (LT), as compared to that in the older patients (≥ 50years). Moreover, effectiveness of postoperative radiation therapy (PRT) after radical prostatectomy (RP) was also assessed in patients aged < 50years. Within the Surveillance, Epidemiology, and End results database (2004-2014), non-metastatic cT3-4 LAPC patients treated with LT (RP, RT or RP+RT) were identified. After propensity score matching (PSM), cancer-specific mortality (CSM), overall survival (OS), and other-cause mortality (OCM) rates were assessed. Multivariable competing risk regression (MVA CRR) model was also used in our analysis. 1507 younger (< 50years) and 34833 older (≥ 50years) LAPC patients treated with LT were identified. Younger patients with LAPC had overall more aggressive disease features than their older counterparts. After PSM, younger patients yielded higher cumulative CSM rates than the older patients (P = 0.046). However, OS and cumulative OCM rates were significantly higher (P = 0.038 and P < 0.0001, respectively) in the older cohort. In the MVA CRR model, younger patients yielded higher CSM (P = 0.02). Specifically, younger patients resulted in higher CSM in Gleason score 8-10, cT3b/4 stage, cN1 stage, and patients treated with RP. No statistically significant differences were found in patients treated with RP versus RP+PRT in all parameters. LAPC patients aged < 50years yielded higher CSM after LT, specifically after RP, compared with the older counterparts (≥ 50years). No significant differences were observed in RP versus RP+PRT regarding survival outcomes in our analysis.

Colorectal cancer outcomes in nonagenarian patients: A case series

BackgroundIncreased life expectancy and improved medical management of co-morbidities has led to an increasing number of nonagenarian patients with colorectal cancer being considered for surgical intervention. This study aims to describe the morbidity and mortality of nonagenarians who had operative and non-operative management for colorectal cancer. Materials and MethodsA retrospective study of consecutive colorectal cancer patients from 2010 to 2016 in a district general hospital in Scotland who were 90 years old or above was performed. Demographic and perioperative data were obtained from case note review. Survival analysis and multivariable regression was conducted to determine factors associated with cancer-specific and all-cause mortality. ResultsForty-nine patients were identified; 24 patients underwent operative management (median age: 91) while 25 received non-operative management (median age: 92). Fifteen patients (62.5%) had an elective operation, and 8 (37.5%) had an urgent or emergency procedure. None of the patients treated operatively suffered a significant complication or anastomotic leakage. Median hospital stay was 14 days. Five patients (20.8%) required a higher level of care in the community following discharge. Surgical mortality within 30 days was 4.2%. Patients undergoing an elective operation had a significantly improved survival compared to those undergoing an emergency operation or non-operative management. On multivariable analyses, non-operative management, and presence of metastases at diagnosis were associated with higher cancer-specific mortality. ConclusionElective operative management for carefully selected nonagenarian patients with colorectal cancer is generally acceptable in terms of morbidity and mortality. The majority of operatively managed patients returned to the same functional level of care following discharge. Patients with metastases at the outset and those requiring emergency surgery have a poorer prognosis.

The association between diabetes, comorbidities, body mass index and all-cause and cause-specific mortality among women with endometrial cancer

ObjectiveAlthough endometrial cancer (EC) is associated with relatively good survival rates overall, women diagnosed with high-risk subtypes have poor outcomes. We examined the relationship between lifestyle factors and subsequent all-cause, cancer-specific and non-cancer related survival. MethodsIn a cohort of 1359 Australian women diagnosed with incident EC between 2005 and 2007 pre-diagnostic information was collected by interview at recruitment. Clinical and survival information was abstracted from women's medical records, supplemented by linkage to the Australian National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific survival (EC death vs. non-EC death) associated with each exposure, overall and by risk group (low-grade endometrioid vs. high-grade endometrioid and non-endometrioid). ResultsAfter a median follow-up of 7.1 years, 179 (13%) women had died, with 123 (69%) deaths from EC. As expected, elevated body mass index (BMI), diabetes and the presence of other co-morbidities were associated with a significantly increased risk of all-cause and non-cancer related death. Women with diabetes had higher cancer-specific mortality rates (HR 2.09, 95% CI 1.31–3.35), particularly those who had were not obese (HR 4.13, 95% CI 2.20–7.76). The presence of ≥2 other co-morbidities (excluding diabetes) was also associated with increased risk of cancer-specific mortality (HR 3.09, 95% CI 1.21–7.89). The patterns were generally similar for women with low-grade and high-grade endometrioid/non-endometrioid EC. ConclusionOur findings demonstrate the importance of diabetes, other co-morbidities and obesity as negative predictors of mortality among women with EC but that the risks differ for cancer-specific and non-cancer related mortality.

MP65-08 THE NEUTROPHIL-TO-LYMPHOCYTE RATIO AS A PROGNOSTIC FACTOR FOR PATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER FOLLOWING RADICAL CYSTECTOMY

Introduction: Pre-treatment neutrophil-to-lymphocyte ratio (NLR) has been associated with adverse pathology or survival in a variety of malignancies, including urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Whether the prognostic value of NLR is retained, or even increased, when measured postoperatively remains not well studied. In this study, we evaluated the association of preoperative and postoperative NLR with oncological outcomes following RC. Methods: 132 consecutive patients with UCB treated with open RC were analyzed. NLR was analyzed both as a continuous variable and as a categorical variable using a cut-off of 2.7 based on previous studies. NLR was recorded as followed: before surgery (within 15 days prior to RC, [NLR1]), postoperatively (within 2 days [NLR2], between 7 and 15 days after RC before discharge [NLR3], few days before the evidence of recurrence or last available follow up [NLR4]. ∆NLR was calculated as the difference between NLR2 and NLR1 (NLR∆1) and between NLR 2 and NLR3 (NLR∆2). Tumour stage, lymphovascular invasion (LVI) and lymph node involvement were collected. Cancer-specific mortality (CSM), all-cause mortality (ACM) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariate logistic regression and Cox proportional hazard models were used to analyze the association of NLR with extravesical disease, LVI, lymph node involvement, recurrence of disease and mortality. Results: During a follow up of 15.9 months, 45 (34.1%) patients had a recurrence of UBC, 60 (45.4%) patients died, 38 (28.8%) of UCB and 22 (16.7%) of other cause. 64 (48.5%) have no evidence of disease at follow-up. When assessed by multivariable analysis NLR1 remained independently associated with a significantly increased risk of extravescical disease (pT 3-4) [OR: 1.4, p<0.01] and Lymphovascular invasion [OR: 1.40, p<0.01]. NLR4 was independently associated with a significantly increased risk of CSM [HR=1.14, p=0.013]. In a postoperative model, NLR3 was found to be an independent predictor of ACM [HR=1.11, 95%, p=0.01]. NLR1 was associated with a significantly increased risk of recurrence in the univariable preoperative model [HR=1.9, p=0.05] while in the postoperative model, NLR4 remained independently associated with a significantly increased risk of recurrence [HR 1.13, p=0.03]. Conclusions: In patients with UCB treated with RC, NLR is associated with more advanced tumour stage, LVI, lymph node metastasis and higher CSM. Furthermore, the variation of NLR after surgery might play a role to predict higher ACM and RFS.

The effect of age on cancer-specific mortality in patients with small renal masses: A population-based analysis.

Contemporary data regarding the effect of age, especially in elderly patients, on cancer-specific mortality (CSM) for pT1a renal cell carcinoma (RCC) are lacking. The objective of the current study is to evaluate CSM in a large population-based cohort of surgically treated pT1a RCC patients according to age groups. Within the Surveillance Epidemiology and End Results database (2000-2013), we identified 37 121 pT1a RCC patients who underwent either partial or radical nephrectomy. The population was stratified into five groups according to decades: <50, 50-59, 60-69, 70-79, and ≥80 years. The effect of age on CSM was evaluated using competing risks regression models according to Fuhrman grade (FG). Analyses were repeated in clear-cell RCC (ccRCC). Patients aged 50-59 (9615), 60-69 (10 762), 70-79 (7096), and ≥80 (1789) years demonstrated higher rate of CSM compared to patients aged <50 (7856) years (hazard ratios [HR] 2.11, 3.04, 4.47, and 7.56, respectively; all p<0.001). The effect of age on CSM in FG 1-2 patients resulted in HRs ranging from 2.01-8.23 for the same age decades (all p< 0.001). Similarly, the effect of age on CSM in FG 3-4 patients resulted in HRs ranging from 2.38-5.92, respectively (all p<0.001). Virtually the same results were recorded in ccRCC patients. Older age is associated with higher CSM in surgically treated patients with pT1a RCC. This effect seems to be more pronounced in patient with FG 1-2 disease. This observation should be considered when making treatment decisions in elderly patients.

Comparison of Partial Versus Radical Nephrectomy Effect on Other-cause Mortality, Cancer-specific Mortality, and 30-day Mortality in Patients Older Than 75 Years

BackgroundHistorically, partial nephrectomy (PN) showed no benefit on other-cause mortality (OCM) in elderly patients with small renal masses. ObjectiveTo test the effect of PN versus radical nephrectomy (RN) on OCM, cancer-specific mortality (CSM), as well as 30-d mortality in patients with nonmetastatic T1a renal cell carcinoma (RCC), aged ≥75 yr old. Design, setting, and participantsWithin the Surveillance, Epidemiology and End Results registry (2004–2014), we identified surgically treated patients with nonmetastatic pT1a RCC aged ≥75 yr. Outcome measurements and statistical analysisWe relied on propensity score (PS) matching to reduce the effect of inherent differences between PN and RN. After PS matching, cumulative incidence, multivariable competing-risks regression (CRR) and logistic regression models were used. LOESS plots graphically depicted the relation between nephrectomy type and OCM after adjustment for all the covariates. Landmark analyses at 6 mo tested for immortal time bias. Results and limitationsOf all 4541 patients, 41.6% underwent PN. After 1:1 PS matching, 2826 patients remained. In multivariable CRR models, lower OCM rates were recorded in PN patients (hazard ratio [HR]: 0.67, confidence interval [CI]: 0.54–0.84; p<0.001). LOESS plots showed lower OCM rates after PN across all examined ages. Lower CSM rates were also recorded in PN patients (HR: 0.64, CI=0.44–0.92; p=0.02). Landmark analyses rejected the hypothesis of immortal time bias. Finally, PN did not result in different 30-d mortality rates (odds ratio: 1.87; CI: 0.79–4.47; p=0.2) versus RN. Data are retrospective. ConclusionsPN results in lower OCM in elderly patients with pT1a RCC. Moreover, PN does not contribute to higher CSM or 30-d mortality in patients aged ≥75 yr. In consequence, PN should be given strong consideration, even in elderly patients. Patient summaryPartial nephrectomy (PN) may protect from renal insufficiency, hypertension, and other unfavorable health outcomes, even in elderly patients. This protective effect results in lower other-cause mortality. Moreover, PN benefits are not undermined by higher cancer-specific mortality or 30-d mortality.