Use of the Decipher genomic classifier among men with prostate cancer in the United States.

BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.

Impact of Relative Dose Intensity of FOLFOX Adjuvant Chemotherapy on Risk of Death Among Stage III Colon Cancer Patients.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines have recommended tailored chemotherapy for stage III high-risk (T4 and/or N2) and low-risk (T1-T3 and N1) colon cancer since 2018. Studies have investigated the effect of relative dose intensity (RDI) of FOLFOX on stage III colon cancer survival, however, none has performed a stratified analysis by risk profiles. This study aims to identify the FOLFOX optimal RDI for high-risk and low-risk stage III colon cancer patients. METHODS: Data on 407 eligible patients, diagnosed with stage III colon cancer in 2011 who received FOLFOX, were collected by 8 population-based cancer registries. Multivariable Cox model and Fine-Gray competing risks model were employed to explore Optimal RDI defined as the lowest RDI administered without significant differences in either overall or cause-specific death. RESULTS: Among the 168 high-risk patients, the optimal RDI cut-off was 70% (HR = 1.59 with 95% CI: 0.69-3.66 in overall mortality; HR = 1.24 with 95% CI: 0.42-3.64 in cause-specific mortality when RDI < 70% vs. RDI ≥ 70%). Among the 239 low-risk patients, none of the evaluated cut-offs were associated with significant differences in risk of death between comparison groups. The lowest assessed RDI was 45%, HR = 0.80; 95% CI: 0.24 to 2.73 for overall mortality and HR = 0.53; 95% CI: 0.06 to 4.95 for cause-specific mortality, when RDI <45% versus RDI ≥45%. CONCLUSIONS: There is no significant harm on the risk of death when reducing RDI by <30% for high-risk patients. For the low-risk patients, we found that RDI as low as 45% did not significantly affect the risk of death.

Risk of cancer death by comorbidity severity and use of adjuvant chemotherapy among women with locoregional breast cancer.

OBJECTIVES: To examine the associations of comorbidity and chemotherapy with breast cancer- and non-breast cancer-related death. MATERIALS AND METHODS: Included were women with invasive locoregional breast cancer diagnosed in 2004 from seven population-based cancer registries. Data were abstracted from medical records and verified with treating physicians when there were inconsistencies and missing information on cancer treatment. Comorbidity severity was quantified using the Adult Comorbidity Evaluation 27. Treatment guideline concordance was determined by comparing treatment received with the National Comprehensive Cancer Network guidelines. Kaplan-Meier method and multivariable Cox proportional hazards regressions were employed for statistical analyses. RESULTS: Of 5852 patients, 76% were under 70years old and 69% received guideline concordant adjuvant chemotherapy. Comorbidity was more prevalent in women age 70 and older (79% vs. 51%; p<0.001). After adjusting for tumor characteristics and treatment, severe comorbidity burden was associated with significantly higher cancer-related mortality in older patients (Hazard Ratio [HR]=2.38, 95% CI 1.08-5.24), but not in younger patients (HR=1.78, 95% CI 0.87-3.64). Among patients receiving guideline adjuvant chemotherapy, cancer-related mortality was significantly higher in older patients (HR=2.35, 95% CI 1.52-3.62), and those with severe comorbidity (HR=3.79, 95% CI 1.72-8.33). CONCLUSIONS: Findings suggest that, compared to women with no comorbidity, patients with breast cancer age 70 and older with severe comorbidity are at increased risk of dying from breast cancer, even after adjustment for adjuvant chemotherapy and other tumor and treatment differences. This information adds to risk-benefit discussions and emphasizes the need for further study of the role for adjuvant chemotherapy in these patient groups.

Clinical and Demographic Factors Associated With Receipt of Non Guideline-concordant Initial Therapy for Nonmetastatic Prostate Cancer.

OBJECTIVES: To determine the extent to which initial therapy for nonmetastatic prostate cancer was concordant with nationally recognized guidelines using supplemented cancer registry data and what factors were associated with receipt of nonguideline-concordant care. METHODS: Initial therapy for 8229 nonmetastatic prostate cancer cases diagnosed in 2004 from cancer registries in 7 states was abstracted as part of the Centers for Disease Control's Patterns of Care Breast and Prostate Cancer study conducted during 2007 to 2009. The National Comprehensive Cancer Network clinical practice guidelines version 1.2002 was used as the standard of care based on recurrence risk group and life expectancy (LE). A multivariable model was used to determine risk factors associated with receipt of nonguideline-concordant care. RESULTS: Nearly 80% with nonmetastatic prostate cancer received guideline-concordant care for initial therapy. Receipt of nonguideline-concordant care (including receiving either less aggressive therapy or more aggressive therapy than indicated) was related to older age, African American race/ethnicity, being unmarried, rural residence, and especially to being in the high recurrence risk group where receiving less aggressive therapy than indicated occurred more often than receiving more aggressive therapy (adjusted OR=4.2; 95% CL, 3.5-5.2 vs. low-risk group). Compared with life table estimates adjusted for comorbidity, physicians tended to underestimate LE. CONCLUSIONS: Receipt of less aggressive therapy than indicated among high-risk group men with >5-year LE based on life table estimates adjusted for comorbidity was a concern. Physicians may tend to underestimate 5-year survival among this group and should be alerted to the importance of recommending aggressive therapy when warranted. However, based on more recent guidelines, among those with low-risk disease, the proportion considered to be receiving less aggressive therapy than indicated may now be lower because active surveillance is now considered appropriate.

KRAS testing and first-line treatment among patients diagnosed with metastatic colorectal cancer using population data from ten National Program of Cancer Registries in the United States.

BACKGROUND: In 2011, the National Comprehensive Cancer Network (NCCN) recommended KRAS testing for metastatic colorectal cancer (mCRC) patients. Our study assessed KRAS testing prevalence and its association with socio-demographic and clinical factors and examined first-line treatment. METHODS: Ten state population-based registries supported by Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) collected detailed cancer information on mCRC cases diagnosed in 2011, including KRAS biomarker testing and first-line treatment from ten central cancer registries. Data were analyzed with Chi-square tests and multivariate logistic regression. RESULTS: Of the 3,608 mCRC cases, 27% (n = 992) had a documented KRAS test. Increased age at diagnosis (p < 0.0001), racial/ethnic minorities (p = 0.0155), public insurance (p = 0.0018), and lower census tract education (p = 0.0023) were associated with less KRAS testing. Significant geographic variation in KRAS testing (p < 0.0001) ranged from 46% in New Hampshire to 18% in California. After adjusting for all covariates, age and residence at diagnosis (both p < 0.0001) remained predictors of KRAS testing. Non-Hispanic Blacks had less KRAS testing than non-Hispanic Whites (OR = 0.77, 95% CI = 0.61-0.97). Among those tested and found to have normal (wild-type) KRAS, 7% received anti-EGFR treatment; none received such treatment among those with KRAS mutated gene. CONCLUSIONS: Despite NCCN guideline recommendations, 73% of mCRC cases diagnosed in 2011 had no documented KRAS test. Disparities in KRAS testing existed based on age, race, and residence at diagnosis. IMPACT: These findings show the capacity of monitoring KRAS testing in the US using cancer registry data and suggest the need to understand the low uptake of KRAS testing, and associated treatment choices during the first year since diagnosis.

Influence of patient, physician, and hospital characteristics on the receipt of guideline-concordant care for inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer for which treatments vary, so we sought to identify factors that affect the receipt of guideline-concordant care. METHODS: Patients diagnosed with IBC in 2004 were identified from the Breast and Prostate Cancer Data Quality and Patterns of Care Study, containing information from cancer registries in seven states. Variation in guideline-concordant care for IBC, based on National Comprehensive Cancer Network (NCCN) guidelines, was assessed according to patient, physician, and hospital characteristics. RESULTS: Of the 107 IBC patients in the study without distant metastasis at the time of diagnosis, only 25.8% received treatment concordant with guidelines. Predictors of non-concordance included patient age (≥70 years), non-white race, normal body mass index (BMI 18.5-25 kg/m(2)), patients with physicians graduating from medical school >15 years prior, and smaller hospital size (<200 beds). IBC patients survived longer if they received guideline-concordant treatment based on either 2003 (p=0.06) or 2013 (p=0.06) NCCN guidelines. CONCLUSIONS: Targeting factors associated with receipt of care that is not guideline-concordant may reduce survival disparities in IBC patients. Prompt referral for neoadjuvant chemotherapy and post-operative radiation therapy is also crucial.

Population-Based Lynch Syndrome Screening by Microsatellite Instability in Patients ≤50: Prevalence, Testing Determinants, and Result Availability Prior to Colon Surgery.

OBJECTIVES: As there are no US population-based studies examining Lynch syndrome (LS) screening frequency by microsatellite instability (MSI) and immunohistochemistry (IHC), we seek to quantitate statewide rates in patients aged ≤50 years using data from a Centers for Disease Control and Prevention-funded Comparative Effectiveness Research (CER) project and identify factors associated with testing. Screening rates in this young, high-risk population may provide a best-case scenario as older patients, potentially deemed lower risk, may undergo testing less frequently. We also seek to determine how frequently MSI/IHC results are available preoperatively, as this may assist with decisions regarding colonic resection extent. METHODS: Data from all Louisiana colorectal cancer (CRC) patients aged ≤50 years diagnosed in 2011 were obtained from the Louisiana Tumor Registry CER project. Registry researchers and physicians analyzed data, including pathology and MSI/IHC. RESULTS: Of the 2,427 statewide all-age CRC patients, there were 274 patients aged ≤50 years, representing health care at 61 distinct facilities. MSI and/or IHC were performed in 23.0% of patients. Testing-associated factors included CRC family history (P<0.0045), urban location (P<0.0370), and care at comprehensive cancer centers (P<0.0020) but not synchronous/metachronous CRC or MSI-like histology. Public hospital screening was disproportionately low (P<0.0217). Of those tested, MSI and/or IHC was abnormal in 21.7%. Of those with abnormal IHC, staining patterns were consistent with LS in 87.5%. MSI/IHC results were available preoperatively in 16.9% of cases. CONCLUSIONS: Despite frequently abnormal MSI/IHC results, LS screening in young, high-risk patients is low. Provider education and disparities in access to specialized services, particularly in underserved populations, are possible contributors. MSI/IHC results are infrequently available preoperatively.

Patterns of locoregional treatment for nonmetastatic breast cancer by patient and health system factors.

BACKGROUND: The purpose of this study was to examine local definitive therapy for nonmetastatic breast cancer with the Patterns of Care Breast and Prostate Cancer (POCBP) study of the National Program of Cancer Registries (Centers for Disease Control and Prevention). METHODS: POCBP medical record data were re-abstracted in 7 state/regional registry systems (Georgia, North Carolina, Kentucky, Louisiana, Wisconsin, Minnesota, and California) to verify data quality and assess treatment patterns in the population. National Comprehensive Cancer Network clinical practice treatment guidelines were aligned with American Joint Committee on Cancer staging at diagnosis to appraise care. RESULTS: Six thousand five hundred five of 9142 patients with registry-confirmed breast cancer were coded as having primary disease with stage 0 to IIIA tumors and were included in the study. Approximately 88% received guideline-concordant locoregional treatment. However, this outcome varied by age group: 92% of women < age 50 versus 80% of women ≥ age 70 years old received guideline care (P < 0.01). Characteristics that best discriminated receipt (no/yes) of guideline-concordant care in receiver operating curve analyses were the receipt of breast-conserving surgery (BCS) versus mastectomy (C = 0.70), patient age (C = 0.62), a greater tumor stage (C = 0.60), public insurance (C = 0.58), and the presence of at least mild comorbidity (C = 0.55). Radiation therapy (RT) after BCS was the most omitted treatment component causing nonconcordance in the study population. In multivariate regression, the effects of the treatment facility, ductal carcinoma in situ, race, and comorbidity on nonconcordant care differed by age group. CONCLUSIONS: Patterns of underuse of standard therapies for breast cancer vary by age group and BCS use, with which there is a risk of omission of RT.

The influence of diabetes severity on receipt of guideline-concordant treatment for breast cancer.

Diabetes severity may influence breast cancer treatment choices. We examined whether receipt of guideline-concordant breast cancer treatment varied with diabetes severity. Cancer registry data from seven states regarding 6,912 stage I-III breast cancers were supplemented by medical record abstraction and physician verification. We used logistic regression models to examine associations of diabetes severity with guideline-concordant locoregional treatment, adjuvant chemotherapy, and hormonal therapy adjusted for sociodemographics, comorbidity, and tumor characteristics. We defined guideline concordance using National Comprehensive Cancer Network guidelines, and diabetes and comorbidities using the Adult Comorbidity Evaluation-27 index. After adjustment, there was significant interaction of diabetes severity with age for locoregional treatment (p = 0.001), with many diabetic women under age 70 less frequently receiving guideline-concordant treatment than non-diabetic women. Among similarly aged women, guideline concordance was lower for women with mild diabetes in their late fifties through mid-sixties, and with moderate/severe diabetes in their late forties to early sixties. Among women in their mid-seventies to early eighties, moderate/severe diabetes was associated with increased guideline concordance. For adjuvant chemotherapy, moderate/severe diabetes was less frequently associated with guideline concordance than no diabetes [OR 0.58 (95 % CI 0.36-0.94)]. Diabetes was not associated with guideline-concordant hormonal treatment (p = 0.929). Some diabetic women were less likely to receive guideline-concordant treatment for stage I-III breast cancer than non-diabetic women. Diabetes severity was associated with lower guideline concordance for locoregional treatment among middle-aged women, and lower guideline concordance for adjuvant chemotherapy. Differences were not explained by comorbidity and may contribute to potentially worse breast cancer outcomes.

Influence of race, insurance, socioeconomic status, and hospital type on receipt of guideline-concordant adjuvant systemic therapy for locoregional breast cancers.

PURPOSE: For breast cancer, guidelines direct the delivery of adjuvant systemic therapy on the basis of lymph node status, histology, tumor size, grade, and hormonal receptor status. We explored how race/ethnicity, insurance, census tract-level poverty and education, and hospital Commission on Cancer (CoC) status were associated with the receipt of guideline-concordant adjuvant systemic therapy. METHODS: Locoregional breast cancers diagnosed in 2004 (n = 6,734) were from the National Program of Cancer Registries-funded seven-state Patterns of Care study of the Centers for Disease Control and Prevention. Predictors of guideline-concordant (receiving/not receiving) adjuvant systemic therapy, according to National Comprehensive Cancer Network Guidelines, were explored by logistic regression. RESULTS: Overall, 35% of women received nonguideline chemotherapy, 12% received nonguideline regimens, and 20% received nonguideline hormonal therapy. Significant predictors of nonguideline chemotherapy included Medicaid insurance (odds ratio [OR], 0.66; 95% CI, 0.50 to 0.86), high-poverty areas (OR, 0.77; 95% CI, 0.62 to 0.96), and treatment at non-CoC hospitals (OR, 0.69; 95% CI, 0.56 to 0.85), with adjustment for age, registry, and clinical variables. Predictors of nonguideline regimens among chemotherapy recipients included lack of insurance (OR, 0.47; 95% CI, 0.25 to 0.92), high-poverty areas (OR, 0.71; 95% CI, 0.51 to 0.97), and low-education areas (OR, 0.65; 95% CI, 0.48 to 0.89) after adjustment. Living in high-poverty areas (OR, 0.78; 95% CI, 0.64 to 0.96) and treatment at non-CoC hospitals (OR, 0.68; 95% CI, 0.55 to 0.83) predicted nonguideline hormonal therapy after adjustment. ORs for poverty, education, and insurance were attenuated in the full models. CONCLUSION: Sociodemographic and hospital factors are associated with guideline-concordant use of systemic therapy for breast cancer. The identification of modifiable factors that lead to nonguideline treatment may reduce disparities in breast cancer survival.