5-year Disease-specific Mortality Research Articles

Trends in incidence and 5‐year mortality in men with newly diagnosed, metastatic prostate cancer—A population‐based analysis of 2 national cohorts

Early detection has increased prostate cancer (PCa) incidence. Randomized trials have demonstrated that early detection reduces the incidence of de novo metastatic PCa. Concurrently, life-prolonging treatments have been introduced for patients with advanced PCa. On a populations-based level, the authors analyzed whether early detection and improved treatments changed the incidence and 5-year mortality of men with de novo metastatic PCa. Men diagnosed with PCa during the periods 1980 to 2011 and 1995 to 2011 were identified in the US Surveillance, Epidemiology, and End Results (SEER) program and the Danish Prostate Cancer Registry (DaPCaR), respectively, and stratified according to period of diagnosis. Age-standardized incidence rates were calculated. Five-year mortality rates for de novo metastatic PCa were analyzed using competing risk analysis. Totals of 426,266 and 47,024 men were identified in SEER and DaPCaR, respectively. Of these, 29,555 and 6874 had de novo metastatic PCa. The incidence of de novo metastatic PCa decreased (from 12.0 to 4.4 per 100,000 men) in the SEER cohort (1980-2011), whereas it increased (from 6.7 to 9.9 per 100,000 men) in the DaPCaR cohort (1995-2011). Five-year PCa mortality in the SEER cohort was stable for men diagnosed with de novo metastatic PCa from 1980 to 1994 and increased slightly in the latest periods studied (P < .0001), whereas it decreased by 16.6% (P < .0001) in the DaPCaR cohort. Despite earlier detection, de novo metastatic PCa remains associated with a high risk of 5-year disease-specific mortality. The reduced 5-year PCa mortality in the Danish cohort is largely explained by lead-time. Early detection strategies do indeed decrease the incidence of de novo metastatic PCa, as observed in the SEER cohort. This achievement, however, must be weighed against the unsolved issue of overdetection and overtreatment of indolent PCa. Cancer 2018;124:2931-8. © 2018 American Cancer Society.

Treatment of early stage Supraglottic squamous cell carcinoma: meta-analysis comparing primary surgery versus primary radiotherapy

ObjectivesFor early stage supraglottic squamous cell carcinoma (SCC), single modality treatment either in the form of primary organ preservation surgery alone or radiation alone is recommended. Thus, a definite treatment strategy for early stage supraglottic SCC remains undefined. The primary objective of this study was to conduct a systematic review and meta-analysis comparing the oncologic outcomes of surgery and radiotherapy in early stage (Stage I and II) T1 N0 and T2 N0 supraglottic SCC.MethodsSystematic methods were used to identify published and unpublished data. Two reviewers independently screened all titles, abstracts and articles for relevance using predefined criteria. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsFive studies met the inclusion criteria for disease specific mortality with a total of 2864 pooled patients. 5-year disease specific mortality was lower in the surgery group (ORs 0.43, 95% CI 0.31–0.60). Four studies met the inclusion criteria for 5-year overall mortality with a total of 2790 pooled patients. Five-year overall mortality was lower in surgery group (ORs 0.40, 95% CI 0.29–0.55).ConclusionsThis is the first study to examine the management of early stage supraglottic SCC using meta-analytic methodology. Our results suggest that primary surgery may result in decreased disease specific and overall mortality compared to primary radiotherapy.

Complications during neoadjuvant therapy and prognosis following surgery for esophageal cancer.

Previous researchers have focused upon the influence of postoperative complications upon prognosis from esophagectomy, with very little attention paid to the potential negative effects of complications during neoadjuvant therapy. The hypothesis under investigation in this study was that the prognosis after esophageal cancer surgery is negatively influenced by complications causing hospital admission during neoadjuvant therapy. Patients receiving neoadjuvant therapy and surgery for esophageal cancer between 1987 and 2010 were identified from a population-based nationwide Swedish cohort study and followed up until 2016. The association between hematological and nonhematological complications during neoadjuvant therapy and risk of short- and long-term mortality following surgery was analyzed using a multivariable Cox proportional hazards model, providing hazard ratios (HRs) with 95% confidence intervals (CIs). The HRs were adjusted for appropriate confounding variables.Among 587 patients, complications during neoadjuvant therapy requiring emergency hospitalization affected 65 (12%) patients. Hematological complications were associated with an increased 90-day overall mortality (HR=5.60; 95% CI 1.27-24.75), particularly in subgroups of patients of tumor stage 0-II, adenocarcinoma, and radical and nonradical resection margins, and rendered increased 5-year disease-specific mortality specifically for esophageal adenocarcinoma (HR=3.22; 95% CI 1.00-10.40). Occurrence of nonhematological complications was followed by an increase in 5-year mortality (HR=2.35; 95% CI 1.15-4.81) in poor prognostic groups (tumor stage III-IV). There was no increased 5-year mortality following hematological or nonhematological complications in other subgroups of patients. Complications during neoadjuvant therapy may adversely impact short and long-term mortality in subgroups of patients with esophageal cancer receiving esophagectomy. Patient selection, optimization of neoadjuvant therapy, and timing of surgical resection, remain important areas for future development in the management of esophageal cancer.

Surgery during holiday periods and prognosis in oesophageal cancer: a population-based nationwide Swedish cohort study

ObjectivePrevious studies indicate an increased short-term and long-term mortality from major cancer surgery performed towards the end of the working week or during the weekend. We hypothesised that the prognosis...

The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma

OBJECTIVE: Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients with localized bone sarcomas and to adjust for potential confounders. MATERIAL AND METHODS: All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils, lymphocytes, and sodium were collected from the patient records. The prognostic values of overall and disease-specific mortality were tested for each individual biomarker as well as for the Glasgow prognostic score (GPS) and for a new composite score incorporating five biomarkers (Aarhus composite biomarker score: ACBS). Adjustments were made for comorbidity as well as other possible prognostic factors, such as size, histological type, margin, chemotherapy, and soft tissue extension, using the Cox proportional hazard model. RESULTS: A total of 172 patients with high- or intermediate-grade localized bone sarcoma were included. Of these patients, 63 were diagnosed with chondrosarcoma and 109 patients with Ewing/osteosarcoma. The median age was 55 years for chondrosarcoma and 19 years for Ewing/osteosarcoma patients. The overall 5-year mortality was 31% [95% confidence interval (CI): 21-44] and 41% (95% CI: 33-51), whereas the 5-year disease-specific mortality was 21% (95% CI: 12-34) and 39% (95% CI: 31-49) for chondrosarcoma and Ewing/osteosarcoma, respectively. Comorbidities were present in 12% of the Ewing/osteosarcoma patients and in 24% of the chondrosarcoma patients. After adjustment for comorbidity and other confounders, it was found that elevated levels of CRP, low hemoglobin, low sodium, high GPS, and high ACBS were associated with increased overall mortality. Furthermore, elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were associated with increased disease-specific mortality. CONCLUSION: Elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were all independent prognostic factors for both overall and disease-specific mortality. ACBS is a new three-level score of five biomarkers, but its value has to be confirmed in an independent data set.

University hospital status and prognosis following surgery for esophageal cancer

BackgroundWe hypothesized that such prognosis is independently improved by surgery conducted within university hospitals. MethodsPatients undergoing esophagectomy for esophageal cancer between 1987 and 2010 with follow-up until 2014 were identified from population-based nationwide Swedish cohort study. The association between university hospital status in and mortality was analyzed using a multivariable Cox-proportional hazards model, providing hazard ratios (HRs) with 95% confidence intervals (CIs). The HRs were adjusted for surgeon volume as well as age, comorbidity, tumor stage, histological subtype, neoadjuvant therapy and calendar period. ResultsAmong 1820 included patients, 989 (54.3%) had surgery at one of the six university hospitals. Of the 83 and 569 patients operated on by the higher surgeon volume (17–46 cases) and middle surgeon volume groups (7–16 cases), 60 (72.3%) and 430 cases (75.6%) respectively were performed within university hospitals. University hospitals status indicated a non-significant reduction in all-cause 90-day mortality (HR = 0.82, 95% CI 0.61–1.10), but all-cause 5-year (HR = 0.94, 95% CI 0.83–1.05) and disease-specific 5-year mortality (HR = 1.00, 95% CI 0.88–1.14) were similar to non-university hospitals. Higher surgeon volume (17–46 cases), showed non-significant reductions in all-cause 90-day (HR = 0.49, 95% CI 0.21–1.14), all-cause 5-year (HR = 0.80, 95% CI 0.61–1.06) and disease-specific 5-year mortality (HR = 0.81, 95% CI 0.60–1.09). ConclusionsThis study found no improvements in long-term mortality from esophagectomy performed within university hospitals after adjustment for surgeon volume and other confounders.

Weekday of Esophageal Cancer Surgery and Its Relation to Prognosis.

To assess whether weekday of surgery influences long-term survival in esophageal cancer. Increased 30-day mortality rates have been reported in patients undergoing elective surgery later compared with earlier in the week. This population-based cohort study included 98% of all esophageal cancer patients who underwent elective surgery in Sweden in 1987 to 2010, with follow-up until 2014. The association between weekday of surgery and 5-year all-cause and disease-specific mortality was analyzed using a multivariable Cox proportional hazards model, providing hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, comorbidity, tumor stage, histology, neoadjuvant therapy, and surgeon volume. Among 1748 included patients, surgery conducted from Wednesday to Friday entailed 13% increased all-cause 5-year mortality compared with surgery conducted from Monday to Tuesday (HR = 1.13, 95% CI, 1.01-1.26). The corresponding association was strong for early tumor stages (0-I) (HR = 1.59, 95% CI, 1.17-2.16), moderate for intermediate tumor stage (II) (HR = 1.28, 95% CI, 1.07-1.53), and absent in advanced tumor stages (III-IV) (HR = 0.93, 95% CI, 0.79-1.09). The increase in 5-year mortality for each later weekday (discrete variable) was 7% for all tumor stages (HR = 1.07, 95% CI, 1.02-1.12), 24% for early tumor stages (HR = 1.24, 95% CI, 1.09-1.41), 13% for intermediate stage (HR = 1.13, 95% CI, 1.05-1.22), whereas no increase was found for advanced stages (HR = 0.98, 95% CI, 0.92-1.05). The disease-specific 5-year mortality was similar to the all-cause mortality. The increased 5-year mortality of potentially curable esophageal cancer after surgery later in the week suggests that this surgery is better carried out earlier in the week.

Incidence of and survival after glottic squamous cell carcinoma in Denmark from 1971 to 2011—A report from the Danish Head and Neck Cancer Group

AimTo describe the incidence, disease-specific mortality (DSM), and overall survival (OS) of patients with glottic squamous cell carcinomas (SCC) in Denmark from 1971–2011 in a national population-based cohort of consecutive patients. Materials and methodsAll patients diagnosed with glottic SCC stage I–IV between 1971 and 2011 in Denmark were included. Patients were identified from the Danish Head and Neck Cancer database, which has a coverage of approximately 100% of registered glottic cancer in Denmark. Information on vital status and cause of death were updated using patient charts and national registries. ResultsIn total 5132 patients with glottic SCC were included. The yearly number of new cases increased from 107 in the 1970s to 139 in the 2000s. Overall, the incidence increased from 1.9 to 2.6 per 100,000, with a more prominent increase in men (3.5 to 4.7) compared with women (0.4 to 0.6). The 5-year DSM was 16% (15–17%) and the 5-year OS was 63% (61–64). The hazard rate of DSM adjusted for patient characteristics, tumour characteristics and waiting-time was significantly lower in the 2000s (p < 0.01), and the hazard rate of OS was significantly higher (p < 0.01) compared to the earlier decades. Longer waiting-time for treatment (>25 d) significantly increased DSM and reduced OS. ConclusionDespite being highly avoidable with smoking cessation, the incidence of glottic SCC increased in Denmark from 1971–2011. The adjusted hazard rate of DSM and overall death after glottic SCC was significantly lower in the 2000s compared to previous decades. Waiting-time for treatment significantly influenced DSM and OS.

Extent of Lymphadenectomy and Prognosis After Esophageal Cancer Surgery.

The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95% CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95% CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95% CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased mortality rates, and these associations showed dose-response associations. This study indicated that the extent of lymphadenectomy during surgery for esophageal cancer might not influence 5-year all-cause or disease-specific survival. These results challenge current clinical guidelines.

Prognostic factors for local recurrence and mortality in adult soft tissue sarcoma of the extremities and trunk wall

Background and purpose — Previous studies of soft tissue sarcoma (STS) have identified a number of possible prognostic factors; however, the majority of these include highly selected populations, with unclear validation of data and insufficient statistical methods. We identified prognostic factors in a validated, population-based 30-year series of STS treated at a single institution, using an advanced statistical approach.Patients and methods — Between 1979 and 2008, 922 adult patients from western Denmark were treated at the Aarhus Sarcoma Center for non-metastatic STS in the extremities or trunk. The endpoints were local recurrence (LR) and disease-specific mortality (DSM). Prognostic factors were analyzed using a proportional hazard model, including continuous variables as cubic splines. Directed acyclic graphs were used to depict the causal structure.Results — The 5-year LR was 16% and the 5-year DSM was 24%. Important prognostic factors for both LR and DSM were age, duration of symptoms, tumor size, grade, margin, and radiotherapy, while anatomical location (upper, lower extremity, trunk) was prognostic for DSM.Interpretation — In this population-based series of adult, non-metastatic STS, we included directed acyclic graphs, cubic splines, and a competing risk model in order to minimize bias, and demonstrated that these statistical methods are feasible. Using these statistical methods on a large, validated dataset, we excluded depth as a prognostic factor and established that age, duration of symptoms, size, grade, margin, and radiotherapy were important prognostic factors for both local recurrence and disease-specific mortality.

Stage-Stratified Prognosis of Signet Ring Cell Histology in Patients Undergoing Curative Resection for Gastric Adenocarcinoma

The prognosis of signet ring cell (SRC) gastric adenocarcinoma is regarded as poor, although studies addressing outcomes in relation to non-SRC tumors are conflicting. Our objective was to compare the survival of SRC tumors with stage-matched intestinal-type tumors in a cohort of Western patients. Review of a prospectively maintained database identified 569 patients undergoing curative resection (R0) from 1990 to 2009. Patients were divided into three histologic groups on the basis of the Lauren classification: SRC (n = 210), intestinal well- or moderately differentiated (WMD, n = 242) disease, and intestinal poorly differentiated (PD, n = 117) disease. Patient demographics, clinicopathologic features, and postoperative outcomes were determined. Stage-stratified disease-specific mortality was calculated and multivariate analysis performed. When compared with WMD and PD tumors, SRC tumors were associated with younger age (63 years SRC vs. 71 years WMD and 72 years PD, p < 0.0001) and with female sex (58 % SRC vs. 40 % WMD and 40 % PD, p = 0.0003). Median follow-up was 115 months. Patients with stage Ia SRC lesions had a better 5-year disease-specific mortality compared with stage-matched intestinal-type tumors (0 % SRC vs. 8 % WMD and 24 % PD, p = 0.001). In contrast, SRC patients with stage III disease fared significantly worse (78 % SRC vs. 54 % WMD and 72 % PD, p = 0.001). On multivariate analysis, the risk of death from gastric cancer comparing all three groups was lowest for SRC in stage I and highest for SRC in stage III disease (stage III hazard ratio: SRC 1 vs. 0.47 WMD and 0.85 PD). When compared with intestinal-type tumors, SRC tumors at early stages are not necessarily associated with poor outcomes.

Nomogram for predicting 5-year disease-specific mortality after primary surgery for epithelial ovarian cancer

ObjectiveTo develop a nomogram based on established prognostic factors to predict the probability of 5-year disease-specific mortality after primary surgery for patients with all stages of epithelial ovarian cancer (EOC) and compare the predictive accuracy with the currently used International Federation of Gynecology and Obstetrics (FIGO) staging system. MethodsUsing a prospectively kept database, we identified all patients with EOC who had their primary surgery at our institution between January 1996 and December 2004. Disease-specific mortality was estimated using the Kaplan–Meier method. Twenty-eight clinical and pathologic factors were analyzed. Significant factors on univariate analysis were included in the Cox proportional hazards regression model, which identified factors utilized in the nomogram. The concordance index (CI) was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. ResultsA total of 478 patients with EOC were included. The most predictive nomogram was constructed using seven variables: age, FIGO stage, residual disease status, preoperative albumin level, histology, family history suggestive of hereditary breast/ovarian cancer (HBOC) syndrome, and American Society of Anesthesiologists (ASA) status. This nomogram was internally validated using bootstrapping and shown to have excellent calibration with a bootstrap-corrected CI of 0.714. The CI for FIGO staging alone was significantly less at 0.62 (P=0.002). ConclusionWe have developed an all-stage nomogram to predict 5-year disease-specific mortality after primary surgery for epithelial ovarian cancer. This tool is more accurate than FIGO staging and should be useful for patient counseling, clinical trial eligibility, postoperative management, and follow-up.

Disease-Specific Survival in Patient-Detected Breast Cancer

Background Patient-detected breast cancer is not well described, and its association with survival is not known. Patients and Methods Initial breast cancer detection methods were extracted from patient chart notes in a registry cohort of women aged 40-93 with primary invasive breast cancer seen at the community-based regional cancer center between 1990 and 1999 (N = 2228). Patients were followed for vital status and recurrence (current as of 2003/2004) with a mean follow-up of 7.6 years. Physician-detected breast cancers were excluded from the analysis (n = 231). Results Forty-six percent of cases were patient detected (n = 1019), and 54% were mammography detected (n = 1209). Those with patient-detected disease received more aggressive treatment (combined radiation and chemotherapy; 49% vs. 23%; P < 0.001) and were twice as likely to have a modified radical mastectomy (41% vs. 20%; P < 0.001). Patient-detected cases were more likely to have a disease recurrence (5-year recurrence rate: 13% vs. 6%; log-rank test, 30.51; P < 0.001) and were more likely to die of disease (5-year disease-specific mortality rate: 8% vs. 3%; log-rank test, 34.7; P < 0.001). In a Cox proportional hazards model, detection method was not associated with risk of breast cancer—related death. Conclusion Patient-detected breast cancer appears to be a more virulent form of breast cancer than mammography-detected breast cancer with higher recurrence and mortality risk despite more aggressive treatment.

Prognosis of patients with resected non-small cell lung cancer: Impact of clinical and pathologic variables

The objective of this study was to determine whether AJCC staging, supplemented by additional clinical and pathologic variables could identify a subpopulation of pathologically staged NSCLC patients who had been resected for cure with a low risk (<20%) of 5-year disease specific mortality. The Surveillance, Epidemiology, and End Results (SEER) registry was analyzed to identify and evaluate the disease specific 5-year mortality of 17,130 patients with resected and pathologically defined Stage I-IIIA disease initially diagnosed from 1988 to 1997. The analyses showed that American Joint Commission on Cancer (AJCC) T and N defined stage Stage I-IIIA subgroups had approximately a 30, 60, and 75% 5-year disease specific mortality, respectively. The 5,366 Stage IA patients were identified as having a 5-year disease specific mortality of 25%. Further multivariate analyses of Stage IA cases showed predictors of favorable outcome to be tumor size (< 10 mm), histologic grade (well differentiated), and histologic subtype (bronchoalveolar cell). Subgroups identified with two or all three of these additional features had an approximately 10% 5-year lung cancer specific mortality. Although nearly all patient subgroups with Stages I-IIIA resected and pathologically staged NSCLC have substantial (>20%) risk of death from their cancer within 5 years of diagnosis, for Stage IA patients additional information (tumor size, histologic grade, and histologic subtype) allows additional refinement in prognostic estimates and identification of some low risk subgroups.

Primary Tracheal Malignant Neoplasms: The University of Texas MD Anderson Cancer Center Experience

Primary malignant neoplasms of the trachea are very rare and data relating to them are limited. This study was conducted to review the presentation, management, and outcomes of primary tracheal cancers at our institution, a large multidisciplinary cancer center. Retrospective chart review was conducted for all patients found to have a pathologic diagnosis of primary tracheal malignancy. Since 1945, 74 patients were diagnosed with primary tracheal cancers. Among these, 34 (45.9%) were squamous cell carcinomas, 19 (25.7%) were adenoid cystic carcinomas, and 21 (28.4%) were of other histologic types. Presenting symptoms were most frequently dyspnea (55.4%), hemoptysis (48.6%), cough (41.9%), and hoarseness (35.1%). Most patients (77.3%) were former or current smokers, particularly those with squamous cell carcinoma (93.3%). For the entire group of 74 patients, the 5-year disease-specific mortality rate was 72.9% and the 5-year all-cause mortality rate was 79.3%. Patients who had adenoid cystic carcinoma and those with cervical primaries had better rates of disease-specific and overall survival than others (p = 0.036 and 0.006 for the former patient group and p = 0.006 and 0.030 for the latter patient group). Among patients with incident disease treated at our institution (n = 45), those undergoing primary operation with adjuvant radiotherapy appeared to have better disease-specific and overall survival rates compared with those undergoing primary radiotherapy with or without chemotherapy (p = 0.0002 and 0.0003, respectively). Although those undergoing operation and receiving radiotherapy did better than those undergoing operation alone, the difference was not statistically significant. Primary tracheal cancers are very rare, and our results should be viewed with caution, given that our population comprised a small heterogeneous group treated over a 60-year period. Although squamous cell carcinoma was the most common pathology in smokers, adenoid cystic carcinoma was more prevalent among nonsmokers. Operation with adjuvant postoperative radiotherapy is recommended for most patients.