Revisiting the AJCC staging system of adrenocortical carcinoma.

OBJECTIVE: To evaluate the performance characteristics of AJCC 7th and 8th staging systems among patients with adrenal cortical carcinoma. METHODS: Surveillance, Epidemiology, and End Results (SEER) 18-registry was accessed and patients with adrenocortical carcinoma who were diagnosed 2010-2015 with complete information about AJCC 7th staging system were included. AJCC 8th staging system information was then reconstructed for each patient using available TNM staging variables. Kaplan-Meier overall survival estimates, multivariable Cox regression analysis, and concordance index (C-statistic) were used to examine the performance characteristics of both staging systems. RESULTS: A total of 574 patients with a diagnosis of adrenocortical carcinoma were included in the current analysis. Using Kaplan-Meier survival estimates, overall survival was compared among different AJCC stages for both versions; and the P value was significant (< 0.001) for both comparisons. C-statistic was then calculated for both staging systems and the results were as follows: for AJCC 7th version: 0.726 (95% CI 0.683-0.769); and for AJCC 8th version: 0.745 (95% CI 0.704-0.786). Patients with M1 disease (stage IV according to AJCC 8th edition) were then divided according to the extent of distant metastases into single versus multiple sites of metastases. Using Kaplan-Meier survival estimates, patients with a single site of metastases have better overall survival (P = 0.006). A C-statistic for a hypothetical modification of AJCC 8th staging system subdividing stage IV patients into IVA and IVB based on the number of metastatic sites was: 0.753 (95% CI 0.713-0.794). CONCLUSIONS: There is a minimal difference in the prognostic performance between both versions of the AJCC staging system. Subdivision of stage IV cancer into stage IVA and IVB (according to the number of organs with metastatic deposits) should be considered in subsequent versions of adrenocortical carcinoma staging.

Geographic Variations of Potentially Curative Treatments for Hepatocellular Carcinoma in the United States: A SEER-Medicare Study.

BACKGROUND: Transplantation, surgical resection, radiofrequency ablation, and percutaneous ethanol injection are generally considered potentially curative treatments for patients with hepatocellular carcinoma (HCC). With the increasing incidence of HCC, it is critical to investigate geographic variations in curative treatments and their associations with survival among patients. METHODS: A total of 6,782 patients with HCC during 2004 to 2011 were identified in the SEER-Medicare linked database and placed in quartiles based on the proportions undergoing potentially curative treatments per hospital referral region (HRR). Hierarchical Cox proportional hazards models were used to examine the association between regional potentially curative treatment patterns and survival across quartiles. RESULTS: An average of 16.9% of patients with HCC underwent potentially curative treatments during 2004 to 2011, varying substantially from 0% to 34.5% across HRRs. Compared with patients residing in the lowest-quartile regions, those in the highest-quartile regions were more likely to be of other races (vs white or black), be infected with hepatitis B virus, and have more comorbidities. The 5-year survival was 4.7% in the lowest-quartile regions and 11.4% in the highest-quartile regions (P<.001). After controlling for confounders, patients in the highest-quartile regions had a lower risk of mortality (adjusted hazard ratio, 0.78; 95% CI, 0.72-0.85). CONCLUSIONS: Patients with HCC who resided in HRRs with higher proportions of potentially curative treatments had better survival. Given its proven survival benefits, prompt clinical and policy actions are needed to reduce variations in treatment utilization.

Trends in Risks for Second Primary Cancers Associated With Index Human Papillomavirus-Associated Cancers.

Importance: In the last 4 decades, survival among patients with human papillomavirus (HPV)-associated cancers has improved, while the incidence of these cancers has increased among younger cohorts. Among survivors of HPV-associated cancers, persistent HPV infection may remain a risk factor for preventable HPV-associated second primary cancers (HPV-SPCs). Objectives: To investigate the risk of HPV-SPCs among survivors of HPV-associated index cancers and to test the hypothesis that the HPV-SPC risk among these persons has increased over the last 4 decades. Design, Setting, and Participants: A retrospective cohort study of 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to identify patients with HPV-associated (cervical, vaginal, vulvar, oropharyngeal, anal, and penile) cancers diagnosed from January 1, 1973, through December 31, 2014. The dates of analysis were July 1, 2017, to January 31, 2018. Main Outcomes and Measures: The HPV-SPC risk was quantified by calculating standard incidence ratios (SIRs) and excess absolute risks (EARs) per 10 000 person-years at risk (PYR). The HPV-SPC risk by time was estimated using Poisson regression. Results: From 113 272 (73 085 female and 40 187 male) survivors of HPV-associated cancers, 1397 women and 1098 men developed HPV-SPCs. The SIRs for HPV-SPCs were 6.2 (95% CI, 5.9-6.6) among women and 15.8 (95% CI, 14.9-16.8) among men. The EARs were 18.2 per 10 000 PYR for women and 53.5 per 10 000 PYR for men. Among both women and men, those who had index oropharyngeal cancers had the highest HPV-SPC risk (SIR, 19.8 [95% CI, 18.4-21.4] and EAR, 80.6 per 10 000 PYR among women; SIR, 18.0 [95% CI, 16.9-19.1] and EAR, 61.5 per 10 000 PYR among men). Women who had index cervical cancers and men who had index anal cancers had the lowest HPV-SPC risk (SIR, 2.4 [95% CI, 2.2-2.7] and EAR, 4.5 per 10 000 PYR among women; SIR, 6.5 [95% CI, 4.7-8.8] and EAR, 18.5 per 10 000 PYR among men). Both women and men who had index HPV-associated cancers of any kind had a significantly higher risk of oropharyngeal HPV-SPCs. Over the last 4 decades, the risk of developing most types of HPV-SPCs after index cervical, vaginal, and vulvar cancers increased. Conclusions and Relevance: According to this study, the HPV-SPC risk among survivors of HPV-associated cancers is significant, implying that persistent HPV infection at multiple sites may be associated with HPV-SPCs. These findings have the potential to inform surveillance recommendations for survivors of HPV-associated cancers.

Validation of the prognostic value of new sub-stages within the AJCC 8th edition of non-small cell lung cancer

Background. The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for non-small cell lung cancer (NSCLC) has been released. The current study tried to validate the prognostic significance of the new system among patients registered within the surveillance, epidemiology and end results (SEER) database. Methods. SEER database (2010-2013) has been accessed through SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the collaborative stage descriptions. Overall and lung cancer-specific survival analyses according to both 7th and 8 th editions were conducted through Kaplan-Meier analysis and multivariate analysis was conducted through a Cox proportional hazard model. Results. A total of 127,096 patients with NSCLC were identified in the period from 2010 to 2013. For overall survival assessment according to the 8th edition, P values for all pair-wise comparisons among different stages were significant (<0.0001) except for the comparisons between stage IB and IIA (P = 0.146); stage IIA and IIB (P = 0.165). For lung cancer-specific survival according to the 8th edition, P values for all pair-wise comparisons among different stages were significant (<0.001). Among patients with stage I disease, multivariate analysis for factors affecting overall and lung cancer-specific survival among patients with stage I disease was conducted. The following factors were associated with worse overall and lung cancer-specific survival: age ≥70 years, more advanced stage, male gender, squamous histology, no surgery and no radiotherapy (P < 0.0001 for all factors). Conclusion. This SEER analysis supports the prognostic significance of the added sub-stages described within AJCC 8th edition stages I and III. Further work is needed to incorporate molecular markers and personalize the future editions of the AJCC staging system (AU)

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The Surveillance, Epidemiology, and End Results (SEER) Program and Pathology: Toward Strengthening the Critical Relationship.

The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute collects data on cancer diagnoses, treatment, and survival for approximately 30% of the United States (US) population. To reflect advances in research and oncology practice, approaches to cancer control are evolving from simply enumerating the development of cancers by organ site in populations to including monitoring of cancer occurrence by histopathologic and molecular subtype, as defined by driver mutations and other alterations. SEER is an important population-based resource for understanding the implications of pathology diagnoses across demographic groups, geographic regions, and time and provides unique insights into the practice of oncology in the US that are not attainable from other sources. It provides incidence, survival, and mortality data for histopathologic cancer subtypes, and data by molecular subtyping are expanding. The program is developing systems to capture additional biomarker data, results from special populations, and expand biospecimen banking to enable cutting-edge cancer research and oncology practice. Pathology has always been central and critical to the effectiveness of SEER, and strengthening this relationship in this modern era of cancer diagnosis could be mutually beneficial. Achieving this goal requires close interactions between pathologists and the SEER program. This review provides a brief overview of SEER, focuses on facets relevant to pathology practice and research, and highlights the opportunities and challenges for pathologists to benefit from and enhance the value of SEER data.

Trade-Off between Treatment of Early Prostate Cancer and Incidence of Advanced Prostate Cancer in the Prostate Screening Era.

PURPOSE: Prostate specific antigen screening has led to the early detection of prostate cancer. However, there has also been concern about the over diagnosis and overtreatment of patients with indolent cancers. We performed a population based analysis to evaluate the trade-off between excess treatment and prevention. MATERIALS AND METHODS: We used the CDC (Centers for Disease Control and Prevention) Behavioral Risk Factor Surveillance System survey from 2001 to 2010 to determine rates of prostate specific antigen screening. We used the SEER database to identify all patients diagnosed with prostate cancer from 1988 (pre-prostate specific antigen screening) to 2010. Demographic, staging and treatment data were collected. Cases were classified as early (low/intermediate risk), high risk, node positive or metastatic disease. RESULTS: Prostate specific antigen screening rates in the last 2 years were 54% for men older than 40 years, including 71% for those older than 60, and did not vary during 2001 to 2010. Comparing 1988 and 2000 to 2010, per 100,000 men the incidence of early prostate cancer increased (61.7 to 113.7), while high risk cancer increased (20.7 to 28.2), node positive cancer decreased (3.7 to 1.8) and metastatic cancer decreased (13.6 to 6.2). The rate of definitive primary treatment (radical prostatectomy or radiation therapy) for men with early cancer increased from 47% to 67% (p <0.001). CONCLUSIONS: Prostate specific antigen screening has led to an additional diagnosis of 5.8 cases of early stage cancer and 3.9 cases receiving treatment for early cancer for every 1 less case of stage IV disease at initial diagnosis. This ratio represents the worst-case scenario for overtreatment and provides a quantitative basis for studying the effect of prostate specific antigen screening.

Availability of TNM Staging Data Elements in the Medical Record and Training Needs Assessment: Results from the 2014 SEER Training Needs Assessment for TNM Study.

BACKGROUND: In 2016, the cancer registry community will directly assign T, N and M components of stage. The Surveillance, Epidemiology, and End Results program implemented a field study to determine how often T, N and M were not available in the medical record, requiring the registrar to directly assign clinical or pathologic TNM stage components. The field study also identified specific training needs. METHODS: T, N and M status were collected from multiple sources within medical records for a total of 280 cases, 56 each from breast, prostate, colon, lung, and ovarian cancer. TNM data elements were also directly assigned by a series of reviewers and by study participants using the medical records with TNM information redacted. Availability of physician-assigned TNM was estimated from the medical record. Also, participant responses were compared to preferred answers. RESULTS: Pathologic T, N and M were available more often in the medical records than were clinical values and varied by site. Pathologic T and N were available for about two-thirds of the cases, but the clinical elements were available for only about 20% of cases. The agreement between participant responses and review panel assignments varied by data element and cancer site. Agreement was modest for most data elements and cancer sites, ranging from 54% for clinical T to 92% for clinical M for all cancer sites combined. CONCLUSIONS: The data elements for TNM staging and stage group were often missing from the medical records, so registrars in the field will need to assign TNM frequently. Furthermore, the results of this study strongly suggest that more training is required, even among those who currently assign TNM.

Unveiling SEER-CAHPS®: a new data resource for quality of care research.

BACKGROUND: Since 1990, the National Cancer Institute (NCI) and Centers for Medicare and Medicaid Services (CMS) have collaborated to create linked data resources to improve our understanding of patterns of care, health care costs, and trends in utilization. However, existing data linkages have not included measures of patient experiences with care. OBJECTIVE: To describe a new resource for quality of care research based on a linkage between the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS®) patient surveys and the NCI's Surveillance, Epidemiology and End Results (SEER) data. DESIGN: This is an observational study of CAHPS respondents and includes both fee-for-service and Medicare Advantage beneficiaries with and without cancer. The data linkage includes: CAHPS survey data collected between 1998 and 2010 to assess patient reports on multiple aspects of their care, such as access to needed and timely care, doctor communication, as well as patients' global ratings of their personal doctor, specialists, overall health care, and their health plan; SEER registry data (1973-2007) on cancer site, stage, treatment, death information, and patient demographics; and longitudinal Medicare claims data (2002-2011) for fee-for-service beneficiaries on utilization and costs of care. PARTICIPANTS: In total, 150,750 respondents were in the cancer cohort and 571,318 were in the non-cancer cohort. MAIN MEASURES: The data linkage includes SEER data on cancer site, stage, treatment, death information, and patient demographics, in addition to longitudinal data from Medicare claims and information on patient experiences from CAHPS surveys. KEY RESULTS: Sizable proportions of cases from common cancers (e.g., breast, colorectal, prostate) and short-term survival cancers (e.g., pancreas) by time since diagnosis enable comparisons across the cancer care trajectory by MA vs. FFS coverage. CONCLUSIONS: SEER-CAHPS is a valuable resource for information about Medicare beneficiaries' experiences of care across different diagnoses and treatment modalities, and enables comparisons by type of insurance.

Algorithm for identifying chemotherapy/biological regimens for metastatic colon cancer in SEER-Medicare.

BACKGROUND: Metastatic colon cancer (mCC) patients often receive multiple lines of chemotherapy/biological treatment (TX), yet subsequent TX lines have not been sufficiently examined using SEER-Medicare data. We developed an algorithm that identifies the number and type of TX lines received by mCC patients. METHODS: The algorithm rules for detecting TX lines were developed a priori and applied to SEER-Medicare data for 7951 elderly mCC patients, diagnosed in 2003-2007 and followed through 2009. Statistical analysis estimated the relationship between the number of treatments received and patient characteristics. Sensitivity analyses examined how results changed when different algorithm rules were used. RESULTS: Only 41% (3266) of mCC patients received any chemotherapy/biologics treatment; 1440 (18% of all, 44% of treated) and 274 (3% of all, 8% of treated) received second-line and third-line treatment, respectively. Initial and subsequent treatment regimens varied widely. Results were robust to alterations in the algorithm. CONCLUSIONS: The number of drugs used to treat cancer patients has increased during the past decade. Patients may have several TX lines with complex regimens. More guidance is needed with regard to identifying and studying these interventions using SEER-Medicare data. By proposing 1 approach to categorizing TX lines for mCC patients, we hope to empower the scientific community and to advance the use of SEER-Medicare data for health outcomes research.

Prognosis of patients with thyroid cancer who do not undergo surgical treatment: a SEER database analysis

BACKGROUND: The treatment for thyroid cancer is surgical. However, some patients do not undergo operations because of comorbidities or other reasons. There is little information about the prognosis of these patients. The aim of the present study was to describe patients with well differentiated thyroid carcinoma who did not undergo surgical treatment and to identify differences in prognostic variables and survival compared with patients treated surgically. METHODS: We conducted a retrospective review of a prospective cohort collected by the National Cancer Institute obtained from the Surveillance, Epidemiology and End Results (SEER) Program. All patient files with a diagnosis of thyroid cancer were selected (38,493 cases). Finally, 12,416 cases were used for the analysis. Treatment was divided into surgical or nonsurgical groups. Five-year survival rates were estimated and classified by the SEER stage. RESULTS: Eighty-six patients did not receive surgical treatment. These patients were older, had more advanced tumours and their treatment was less associated with complementary radiotherapy. Five-year overall survival rates were 96.7% for surgical patients vs. 56.8% for nonsurgical patients (p<0.001). The overall survival in the nonsurgery group for localised tumours decreased 14.9%, for regional tumours decreased 49.9% and for distant tumours decreased 61.8%. DISCUSSION: The patients who did not undergo surgical treatment showed less than 5-year overall survival. The SEER database does not offer information about comorbidities that could explain these differences (AU)

Predictors of axillary lymph node involvement in women with T3 breast cancers: analysis of 1988-2003 SEER data.

BACKGROUND: We investigated characteristics associated with axillary lymph node (LN) status in patients with T3 breast cancers and hypothesized that LN status is an independent predictor of survival. METHODS: Characteristics associated with axillary LN metastasis among women with T3 breast cancers were identified from the 1988-2003 Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was breast cancer-specific mortality. Cox models were used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: A total of 12,778 patients with T3 breast cancers were analyzed (8201 LN+, 3695 LN-, 882 unknown). LN+ patients were more likely to be <50 y, married, and have ER+/PR+, grade 3 invasive ductal cancers (P<0.01 for each). Most patients underwent mastectomy (87.4%). Post-mastectomy radiation was more commonly used in LN+ patients (P<0.01). LN+ patients had higher breast cancer-specific mortality (36.2% versus 16.4%, P<0.01) and were more likely to die during the follow-up period (aHR = 2.87, 95% CI: 2.62-3.15) compared with LN- patients. CONCLUSIONS: Analysis of the SEER database indicated that several patient and tumor characteristics predict a higher likelihood of axillary LN involvement in patients with T3 breast cancers. LN status was an independent predictor of survival in women with T3 breast cancers.

Methodological issues in a retrospective cancer incidence study.

The authors traced incidence of central nervous system cancer in a large occupational cohort of jet engine manufacturing workers from 1976 to 2004 in the 24 US states that comprised 95% of the cohort deaths. The cohort of approximately 224,000 employees was matched with cancer registry data; all central nervous system cancer matches were requested with their diagnostic data. This paper highlights the obstacles encountered while conducting this retrospective cancer incidence study. The authors spent approximately 700 hours completing applications and obtaining the cohort matches. Approximately 70% of the cases were identified in the state in which the facility of interest is located. In addition to the large amount of time involved, identified issues include complicated approval processes, high costs, temporal differences among the registries, and registry agency difficulty in performing the matching. Several states do not allow individual-level data to be used for research purposes. Researchers can gain important cancer incidence information by matching retrospective cohorts to multiple state cancer registries. However, they should carefully weigh the time and costs required and plan accordingly. Despite some serious obstacles, many of which are potentially resolvable, cancer incidence studies of retrospective cohorts using multiple cancer registries are feasible.

Registration and classification of adolescent and young adult cancer cases.

Cancer registries are an important research resource that facilitate the study of etiology, tumor biology, patterns of delayed diagnosis and health planning needs. When outcome data are included, registries can track secular changes in survival related to improvements in early detection or treatment. The surveillance, epidemiology, and end results (SEER) registry has been used to identify major gaps in survival for older adolescent and young adult (AYA) patients compared with younger children and older adults. In order to determine the reasons for this gap, the complete registration and accurate classification of AYA malignancies is necessary. There are inconsistencies in defining the age limits for AYAs although the Adolescent and Young Adult Oncology Progress Review Group proposed a definition of ages 15 through 39 years. The central registration and classification issues for AYAs are case-finding, defining common data elements (CDE) collected across different registries and the diagnostic classification of these malignancies. Goals to achieve by 2010 include extending and validating current diagnostic classification schemes and expanding the CDE to support AYA oncology research, including the collection of tracking information to assess long-term outcomes. These efforts will advance preventive, etiologic, therapeutic, and health services-related research for this understudied age group.

Research recruitment through US central cancer registries: balancing privacy and scientific issues.

Cancer registries are a valuable resource for recruiting participants for public health-oriented research, although such recruitment raises potentially competing concerns about patient privacy and participant accrual. We surveyed US central cancer registries about their policies for research contact with patients, and results showed substantial variation. The strategy used most frequently (37.5% of those that allowed patient contact), which was among the least restrictive, was for investigators to notify patients' physicians and then contact patients with an opt-out approach. The most restrictive strategy was for registry staff to obtain physician permission and contact patients with an opt-in approach. Population-based studies enhance cancer control efforts, and registry policies can affect researchers' ability to conduct such studies. Further discussion about balanced recruitment approaches that protect patient privacy and encourage beneficial research is needed.

Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population.

BACKGROUND: The Surveillance, Epidemiology and End Results (SEER)-Medicare-linked database combines clinical information from population-based cancer registries with claims information from the Medicare program. The use of this database to study cancer screening, treatment, outcomes, and costs has grown in recent years. RESEARCH DESIGN: This paper provides an overview of the SEER-Medicare files for investigators interested in using these data for epidemiologic and health services research. The overview includes a description of the linkage of SEER and Medicare data and the files included as part of SEER-Medicare. The paper also describes the types of research projects that have been undertaken using the SEER-Medicare data. The overview concludes with a comparison of selected characteristics of elderly persons residing in the SEER areas to the US total aged. RESULTS: The paper identifies a number of potential uses of the SEER-Medicare data. The comparison of the elderly population in SEER areas to the US total shows that in the SEER areas there are a lower percentage of white persons and individuals living in poverty, and a higher percentage of urban-dwellers than the US total. Elderly persons in the SEER regions also have higher rates of HMO enrollment and lower rates of cancer mortality. CONCLUSIONS: The SEER-Medicare data are a unique resource that can be used for a variety of health services research projects. Although there are some differences between the elderly residing in the SEER areas and the US total, the SEER-Medicare data offer a large population-based cohort that can be used to longitudinally track care for persons over the course of cancer diagnosis, treatment, and follow-up.

Alternatives to a national system of population-based state cancer registries.

To support cancer control efforts, the National Program of Cancer Registries was established to enhance or develop cancer registries in every state. But there is an alternative. State cancer control programs could be adequately planned and evaluated without a cancer registry, and federal support of cancer registration could be selectively provided to registries that provide data needed to monitor cancer incidence and survival for the nation or that serve as a resource for population-based etiologic and cancer control research. The funds saved could be redirected to support the continued collection of high-quality cancer incidence and survival data for the nation as such efforts become more costly and complex in the future, and to expand support of population-based cancer research efforts.