Higher Other-cause Mortality Research Articles

Mortality rates in radical cystectomy patients with bladder cancer after radiation therapy for prostate cancer.

To conduct a population-based study examining cancer-specific mortality (CSM) and other-cause mortality (OCM) differences in patients with radiation-induced secondary bladder cancer (RT-BCa) vs those with primary bladder cancer (pBCa) undergoing radical cystectomy (RC). Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with T2-4N0-3M0 bladder cancer treated with RC, who had previously been treated with external beam radiation therapy (EBRT) or brachytherapy for prostate cancer, as well as patients with T2-4N0-3M0 pBCa treated with RC. Cumulative incidence plots and multivariable competing risks regression (CRR) models were used to assess CSM after additional adjustment for OCM. The same methodology was then repeated based on organ-confined (OC: T2N0M0) and non-organ-confined (NOC: T3-4 and/or N1-3) disease. Of 9957 RC patients, RT-BCa was identified in 347 (3%) compared with 9610 (97%) who had pBCa. In multivariable CRR models, no CSM differences were recorded in the overall comparison (P = 0.8), nor in sub-groups based on OC and NOC disease (P = 0.8 and 0.7, respectively). Conversely, multivariable CRR models identified RT-BCa as an independent predictor of 1.3-fold higher OCM in the overall cohort and of 1.5-fold higher OCM in those with NOC disease. In a sensitivity analysis of patients with NOC disease, EBRT was associated with higher OCM rates (hazard ratio 1.5). By contrast, OCM rates were not different in those with OC disease (P = 0.8). Our study showed that RC for RT-BCa was associated with similar CSM rates as RC for pBCa, regardless of disease stage. However, patients who had undergone EBRT exhibited significantly higher OCM in the NOC sub-group.

Age Does Not Impact Cancer Specific Mortality: From Sub-Distributional and Cause-Specific Hazard Analysis in RCC Patients Undergoing Radical Nephrectomy and Thrombectomy

ObjectiveTo evaluate the impact of age on cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients undergoing radical nephrectomy with thrombectomy (RNTx) for renal cell carcinoma (RCC) with venous thrombus. Patients and MethodsWe retrospectively analyzed data from 196 patients who underwent RNTx for RCC with venous thrombus between 1990 and 2018 at a single tertiary referral center. Patients were grouped into three age groups: <60 years, 60-69 years, and ≥70 years. Clinical and pathological characteristics were compared. The cumulative incidence function (CIF) for CSM and OCM was calculated using the Aalen-Johansen estimator. We employed both sub-distributional hazard (SDH) and cause-specific hazard (CSH) models to evaluate the impact of age on mortality, using hazard ratios (HR) and 95% confidence intervals (CI) quantified associations. ResultsThe median follow-up was 40.5 months. During this time, 105 patients experienced disease progression, 125 had cancer-related deaths, and 155 deceased from any cause. Perioperative outcomes, including ICU admission, 90-day readmission, and 90-day mortality, showed no significant differences among age groups. The CIF for CSM revealed significant differences at 5-year (p = 0.032) but not at 10-years (p = 0.246). OCM increased with age, notably in the oldest group at 10 years (p = 0.045). Multivariable adjusted CSH and SDH models showed no significant differences in CSM among age groups. ConclusionAlthough the CIF for 5-year CSM and 10-year OCM were associated with increasing age, aging does not increase the hazard of CSM in both SDH and CSH models. Perioperative outcome does not differ between all age groups. For RCC with venous thrombus patients, older age alone is not absolute contraindication for surgical intervention. Micro-AbstractThis study assessed the impact of age on cancer-specific and other-cause mortality in patients undergoing radical nephrectomy with thrombectomy for renal cell carcinoma with venous thrombus. Although older age was associated with higher other-cause mortality at 10 years, age did not significantly affect cancer-specific mortality, suggesting that age should not be a contraindication for surgery in these patients. Perioperative outcomes were similar across all age groups.

Other-cause mortality in incidental prostate cancer.

In incidental prostate cancer (IPCa), elevated other-cause mortality (OCM) may obviate the need for active treatment. We tested OCM rates in IPCa according to treatment type and cancer grade and we hypothesized that OCM is significantly higher in not-actively-treated patients. Within the Surveillance, Epidemiology, and End Results database (2004-2015), IPCa patients were identified. Smoothed cumulative incidence plots as well as multivariable competing risks regression models were fitted to address OCM after adjustment for cancer-specific mortality (CSM). Of 5121 IPCa patients, 3655 (71%) were not-actively-treated while 1466 (29%) were actively-treated. Incidental PCa not-actively-treated patients were older and exhibited higher proportion of Gleason sum (GS) 6 and clinical T1a stage. In smoothed cumulative incidence plots, 5-year OCM was 20% for not-actively-treated versus 8% for actively-treated patients. Conversely, 5-year CSM was 5% for not-actively-treated versus 4% for actively-treated patients. No active treatment was associated with 1.4-fold higher OCM, even after adjustment for age, cancer characteristics, and CSM. According to GS, OCM reached 16%, 27%, and 35% in GS 6, 7, and 8-10 not-actively-treated IPCa patients, respectively and exceeded CSM recorded for the same three groups (2%, 6%, and 28%, respectively). Our results quantified OCM rates, confirming that in not-actively-treated IPCa patients OCM is indeed significantly higher than in their actively-treated counterparts (HR: 1.4). These observations validate the use of no active treatment in IPCa patients, in whom OCM greatly surpasses CSM (20% vs. 5%).

Is radiotherapy after radical prostatectomy associated with higher other-cause mortality?

The aim of this study was to reveal the association between the other-cause mortality (OCM) and post-radical prostatectomy (RP) salvage radiotherapy (sRT) in men with prostate cancer (PCa). A retrospective study was carried out with patients who had PCa and underwent RP ± sRT in a high-volume cancer center between 2005 and February 2019. Data from 1955 patients were subjected to a 1:1 matching for age, initial PSA, pathological (p)T/N stages, and ISUP score, which yielding 439 RP + RT (group 1) vs 439 RP-only cases (group 2), without any residual difference. Primary and secondary endpoints of the study were OCM and cancer-specific mortality (CSM). Kaplan-Meier, log-rank, and cox regression tests were used for purpose of the study. The median follow-up time after RP was 5.3years (interquartile range: 4.0-7.3). After matching, of all deaths that occurred during the study period, 16 in group 1 and 35 in group 2 were attributed to other causes (p = 0.006). 5-year OCM rate of patients who received sRT (1.2%) was significantly lower compared to patients that underwent RP-only (4.4%, p < 0.001). 19 versus 16 patients died of PCa, respectively (p = 0.61). There was no CSM risk difference between groups (p = 0.29). Older patients had an increased risk of OCM (hazard ratio [HR]:1.10 [95%CI 1.05-1.17], p < 0.001) and post-RP RT was associated with lower OCM (HR: 0.28 [95%CI 0.15-0.51], p < 0.001) in multivariable model. pT/N stages and ISUP score were strongly associated with CSM, but not with OCM. OCM was not higher in patients who had sRT with or without ADT. Excess OCM in favor of RP-only patients may be cautiously explained with higher-performance status/life expectancy of patients who selected for RT after RP in our cohort.

MP50-06 SURVIVAL OF TESTICULAR PURE TERATOMA VS. MIXED GERM CELL TUMOR PATIENTS ACROSS ALL STAGES

MP50-06 SURVIVAL OF TESTICULAR PURE TERATOMA VS. MIXED GERM CELL TUMOR PATIENTS ACROSS ALL STAGES

Survival of Testicular Pure Teratoma vs. Mixed Germ Cell Tumor Patients in Primary Tumor Specimens across All Stages.

We aimed to test for survival differences between testicular pure teratoma vs. mixed germ cell tumor (GCT) patients in a stage-specific fashion. Pure teratoma and mixed GCT in primary tumor specimens were identified within the Surveillance, Epidemiology, and End Results database (2004-2019). Kaplan-Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models were used. Of 9049 patients, 299 (3%) had pure teratoma. In stage I, II and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 91.6 vs. 97.2%, p < 0.001; stage II: 100 vs. 95.9%, p < 0.001; stage III: 66.8 vs. 77.8%, p = 0.021). In stage I, survival differences originated from higher OCM (6.4 vs. 1.2%; p < 0.001). Conversely in stage III, survival differences originated from higher CSM (29.4 vs. 19.0%; p = 0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 4.83; p < 0.01). Conversely, in stage III, in multivariable CRR models, pure teratoma was associated with higher CSM (HR: 1.92; p = 0.04). In pure teratoma, survival disadvantage in stage I patients relates to OCM. Survival disadvantage in stage III pure teratoma originates from higher CSM.

Radiation therapy after radical prostatectomy is associated with higher other-cause mortality

PurposeTo test the association between external beam radiotherapy (EBRT) after radical prostatectomy (RP) vs RP only on rates of other-cause mortality (OCM) in men with prostate cancer (PCa).Patients and methodsWithin the 2004–2016 Surveillance, Epidemiology, and End Results database, we identified 181,849 localized PCa patients, of whom 168,041 received RP only vs 13,808 who received RP + EBRT. Cumulative incidence plots displayed OCM between RP vs RP + EBRT after propensity score matching for age, PSA, clinical T- and N-stages, and biopsy Gleason scores. Multivariable competing risks regression models addressed OCM, accounting prostate cancer-specific mortality (CSM) as a competing event. Stratifications were made according to low- vs intermediate- vs high-risk groups and additionally according to age groups of ≤ 60, 61–70, and ≥ 71 years, within each risk group.ResultsIn low-, intermediate-, and high-risk patients, RP + EBRT rates were 2.7, 5.4 and 17.0%, respectively. After matching, 10-year OCM rates between RP and RP + EBRT were 7.7 vs 16.2% in low-, 9.4 vs 13.6% in intermediate-, and 11.4 vs 13.5% in high-risk patients (all p < 0.001), which, respectively, resulted in multivariable HR of 2.1, 1.3, and 1.2 (all p < 0.001). In subgroup analyses, excess OCM was recorded in low-risk RP + EBRT patients of all age groups (all p ≤ 0.03), but only in the older age group in intermediate-risk patients (61–70 years, p = 0.03) and finally, only in the oldest age group in high-risk patients (≥ 71 years, p = 0.02).ConclusionExcess OCM was recorded in patients exposed to RT after RP. Its extent was most pronounced in low-risk patients, decreased in intermediate-risk patients, and was lowest in high-risk patients.

A0834 - Radiation therapy after radical prostatectomy is associated with higher other-cause mortality

A0834 - Radiation therapy after radical prostatectomy is associated with higher other-cause mortality

Bladder cancer stage and mortality: urban vs. rural residency

ObjectiveRelative to urban populations, rural patients may have more limited access to care, which may undermine timely bladder cancer (BCa) diagnosis and even survival.MethodsWe tested the effect of residency status (rural areas [RA < 2500 inhabitants] vs. urban clusters [UC ≥ 2500 inhabitants] vs. urbanized areas [UA, ≥50,000 inhabitants]) on BCa stage at presentation, as well as on cancer-specific mortality (CSM) and other cause mortality (OCM), according to the US Census Bureau definition. Multivariate competing risks regression (CRR) models were fitted after matching of RA or UC with UA in stage-stratified analyses.ResultsOf 222,330 patients, 3496 (1.6%) resided in RA, 25,462 (11.5%) in UC and 193,372 (87%) in UA. Age, tumor stage, radical cystectomy rates or chemotherapy use were comparable between RA, UC and UA (all p > 0.05). At 10 years, RA was associated with highest OCM followed by UC and UA (30.9% vs. 27.7% vs. 25.6%, p < 0.01). Similarly, CSM was also marginally higher in RA or UC vs. UA (20.0% vs. 20.1% vs. 18.8%, p = 0.01). In stage-stratified, fully matched CRR analyses, increased OCM and CSM only applied to stage T1 BCa patients.ConclusionWe did not observe meaningful differences in access to treatment or stage distribution, according to residency status. However, RA and to a lesser extent UC residency status, were associated with higher OCM and marginally higher CSM in T1N0M0 patients. This observation should be further validated or refuted in additional epidemiological investigations.

Age-related differences of oncological outcomes in primary extremity soft tissue sarcoma: a multistate model including 6260 patients.

No studies extensively compared the young adults (YA, 18-39 years), middle-aged (40-69 years), and elderly (≥70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-agedand elderly population in patients with primary high-grade eSTS treated with curative intent. In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression. A total of 6260 patients were included in this study. YA presented more often after 'whoops'-surgery or for reresection due to residual disease, and with more deep-seated tumours. Elderly patients presented more often with grade III and larger (≥10cm) tumours. After adjustment for the imbalance in tumour and treatment characteristics the hazard ratio for OS of the middle-aged population is 1.47 (95% confidence interval [CI]: 1.23-1.76) and 3.13 (95% CI: 2.59-3.78) in the elderly population, compared with YA. The effect of age on OS could only partially be explained by the imbalance in the tumour characteristics and treatment variables. The threefold higher risk of elderly could, at least partially, be explained by a higher other-cause mortality. The results might also be explained by a different tumour behaviour or suboptimal treatment in elderly compared with the younger population.

Impact of Comorbidities and Age on Cause-Specific Mortality in Postmenopausal Patients with Breast Cancer.

The aim was to study the impact of comorbidities and age on breast cancer mortality, taking into account competing causes of death. Cohort analysis of Dutch and Belgian patients with postmenopausal, early hormone receptor-positive breast cancer included in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial between 2001 and 2006. This is a randomized controlled trial of patients who had completed local treatment with curative intent and were randomized to receive exemestane for 5 years, or sequential treatment of tamoxifen followed by exemestane for a duration of 5 years. Patients were categorized by number of comorbidities (no comorbidities, 1-2 comorbidities, and >2 comorbidities) and age (<70 years and ≥70 years). Main outcome was breast cancer mortality considering other-cause mortality as competing event; cumulative incidences were calculated using the Cumulative Incidence Competing Risk Methods, and the Fine and Gray model was used to calculate the effect of age and comorbidities for the cause-specific incidences of breast cancer death, taking into account the effect of competing causes of death. Overall, 3,159 patients were included, of which 2,203 (69.7%) were aged <70 years and 956 (30.3%) were aged ≥70 years at diagnosis. Cumulative incidence of breast cancer mortality was higher among patients ≥70 without comorbidities (22.2%, 95% CI, 17.5-26.9) compared with patients <70 without comorbidities (15.6%, 95% CI, 13.6-17.7, reference group), multivariable subdistribution hazard ratio (sHR) 1.49 (95% CI, 1.12-1.97, p = .005) after a median follow-up of 10 years. Use of chemotherapy was lower in older patients (1%, irrespective of the number of comorbidities) compared with younger patients (50%, 44%, and 38% for patients with no, 1-2, or >2 comorbidities, p < .001). Older patients without comorbidities have a higher risk of dying due to breast cancer than younger counterparts, even when taking into account higher competing mortality, while use of chemotherapy in this group was low. These findings underline the need to take into account comorbidities, age, and competing mortality in the prognosis of breast cancer for accurate decision making. Older patients without comorbidity are at increased risk of dying from breast cancer, despite a higher other-cause mortality. This study shows that including age and comorbidity for the assessment of breast cancer mortality and other-cause mortality is indispensable for treatment decision making in older patients. Future prognostic tools for breast cancer prognosis should incorporate these items as well as risk of toxicity of adjuvant chemotherapy to adequately predict outcomes to optimize personalized treatment for older patients with early breast cancer.

Patient function, long-term survival, and use of surgery in patients with kidney cancer.

Beyond age and comorbidity, functionality can shape the long-term survival potential of patients with cancer. Accordingly, herein the authors compared mortality and receipt of cancer-directed surgery according to patient function among older adults with kidney cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2000 through 2009, the authors studied 28,326 elderly subjects with primary kidney cancer. Patient function was quantified using function-related indicators, claims indicative of dysfunction and disability. Adjusting for patient and cancer characteristics, competing risk regression was used to assess the relationship between function-related indicator count and cause-specific mortality and then generalized estimating equations were used to quantify the probability of surgery. A total of 13,619 adult patients (48.1%) with at least 1 function-related indicator were identified. A higher indicator category was associated with older age, greater comorbidity, female sex, unmarried status, lower socioeconomic status, and higher stage of disease (P<.001). Compared with patients with an indicator count of 0, those with an indicator count of 1 (hazard ratio, 1.10; 95% confidence interval [95% CI], 1.04-1.16) and ≥2 (hazard ratio, 1.46; 95% CI, 1.39-1.53) were found to have higher other-cause mortality. Conversely, kidney cancer mortality varied minimally with patient function. Patients with ≥ 2 indicators received cancer-directed surgery less often than those without disability (odds ratio, 0.61; 95% CI, 0.56-0.66), although treatment probabilities remained high for patients with locoregional disease and low for those with metastatic cancer. Among older adults with kidney cancer, functional health stands as a significant predictor of long-term survival. However, receipt of cancer-directed surgery appears largely determined by cancer stage. Patient function should be considered more heavily when determining treatment for older adults with kidney cancer. Cancer 2016;122:3776-3784. © 2016 American Cancer Society.