William R. Carpenter

Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer

CONTEXT There has been rapid adoption of newer radiation treatments such as intensity-modulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies. OBJECTIVE To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment. DESIGN, SETTING, AND PATIENTS Population-based study using Surveillance, Epidemiology, and End Results-Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer. MAIN OUTCOME MEASURES Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy. RESULTS Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score-adjusted analyses (N = 12,976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86-0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65-0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03-1.20). Intensity-modulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73-0.89). In a propensity score-matched comparison between IMRT and proton therapy (n = 1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55-0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy. CONCLUSIONS Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation therapy was associated with less gastrointestinal morbidity and fewer hip fractures but more erectile dysfunction; IMRT compared with proton therapy was associated with less gastrointestinal morbidity.

Effect of Adjuvant Chemotherapy on Survival of Patients With Stage III Colon Cancer Diagnosed After Age 75 Years

PURPOSE Few patients 75 years of age and older participate in clinical trials, thus whether adjuvant chemotherapy for stage III colon cancer (CC) benefits this group is unknown. METHODS A total of 5,489 patients ≥ 75 years of age with resected stage III CC, diagnosed between 2004 and 2007, were selected from four data sets containing demographic, stage, treatment, and survival information. These data sets included SEER-Medicare, a linkage between the New York State Cancer Registry (NYSCR) and its Medicare programs, and prospective cohort studies Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) and the National Comprehensive Cancer Network. Data sets were analyzed in parallel using covariate adjusted and propensity score (PS) matched proportional hazards models to evaluate the effect of treatment on survival. PS trimming was used to mitigate the effects of selection bias. RESULTS Use of adjuvant therapy declined with age and comorbidity. Chemotherapy receipt was associated with a survival benefit of comparable magnitude to clinical trials results (SEER-Medicare PS-matched mortality, hazard ratio [HR], 0.60; 95% CI, 0.53 to 0.68). The incremental benefit of oxaliplatin over non-oxaliplatin-containing regimens was also of similar magnitude to clinical trial results (SEER-Medicare, HR, 0.84; 95% CI, 0.69 to 1.04; NYSCR-Medicare, HR, 0.82, 95% CI, 0.51 to 1.33) in two of three examined data sources. However, statistical significance was inconsistent. The beneficial effect of chemotherapy and oxaliplatin did not seem solely attributable to confounding. CONCLUSION The noninvestigational experience suggests patients with stage III CC ≥ 75 years of age may anticipate a survival benefit from adjuvant chemotherapy. Oxaliplatin offers no more than a small incremental benefit. Use of adjuvant chemotherapy after the age of 75 years merits consideration in discussions that weigh individual risks and preferences.

Effectiveness of Bevacizumab With First-Line Combination Chemotherapy for Medicare Patients With Stage IV Colorectal Cancer

PURPOSE Clinical trials have shown that adding bevacizumab to cytotoxic chemotherapy improves survival for patients with colorectal cancer, although its effectiveness in the Medicare population is uncertain. PATIENTS AND METHODS Using the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked database, we identified 2,526 patients with stage IV colorectal cancer diagnosed between 2002 and 2007 who received first-line combination chemotherapy with a fluoropyrimidine and either irinotecan (33%) or oxaliplatin (67%). Thirty-six percent of patients received bevacizumab with first-line therapy. The primary outcome was overall survival. Secondary outcomes were bevacizumab-associated toxicities, including the incidence of stroke, myocardial infarction, and GI perforation. RESULTS In the primary cohort inclusive of patients diagnosed between 2002 and 2007, bevacizumab with combination chemotherapy was associated with improved overall survival (adjusted hazard ratio [HR], 0.85; 95% CI, 0.78 to 0.93), although the effect was more modest when restricted to years 2004 to 2007 (HR, 0.93; 95% CI, 0.84 to 1.02). The observed survival advantage of bevacizumab was more apparent with irinotecan-based chemotherapy (HR, 0.80; 95% CI, 0.66 to 0.97) than with oxaliplatin-based chemotherapy (HR, 0.96; 95% CI, 0.86 to 1.07). Combination chemotherapy with bevacizumab, versus combination chemotherapy without bevacizumab, was associated with increased risk of stroke (4.9% v 2.5%, respectively; P < .01) and GI perforation (2.3% v 1.0%, respectively; P < .01). Cardiac events and venous thrombosis were not increased with bevacizumab. CONCLUSION The addition of bevacizumab to cytotoxic combination chemotherapy was associated with small improvement in overall survival as well as increased risk of stroke and perforation, but not cardiac events, among Medicare beneficiaries with stage IV colorectal cancer.

Hidden barriers between knowledge and behavior: the North Carolina prostate cancer screening and treatment experience.

Prostate cancer (PC) mortality is much greater for African American than for Caucasian men. To identify patient factors that might account for some of this disparity, men within 6 months of diagnosis were surveyed about health attitudes and behavior.

Comparative Effectiveness of Oxaliplatin vs Non–Oxaliplatin-containing Adjuvant Chemotherapy for Stage III Colon Cancer

BACKGROUND The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain. SUBJECTS AND METHODS Patients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources-the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004-2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan-Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided. RESULTS The survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER-Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR-Medicaid, 82% [n = 54]; NYSCR-Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER-Medicare, and in the NYSCR-Medicare cohort (non-oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy, adjusted HR of death: pooled RCTs: HR = 0.80, 95% CI = 0.70 to 0.92, P = .002; SEER-Medicare: HR = 0.70, 95% CI = 0.60 to 0.82, P < .001; NYSCR-Medicare patients aged ≥65 years: HR = 0.58, 95% CI = 0.38 to 0.90, P = .02). The association between oxaliplatin treatment and better survival was maintained in older and minority group patients, as well as those with higher comorbidity. CONCLUSION The addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant colon cancer treatment in the community.

Association Between Choice of Radical Prostatectomy, External Beam Radiotherapy, Brachytherapy, or Active Surveillance and Patient-Reported Quality of Life Among Men With Localized Prostate Cancer.

Importance Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects. Objective To compare quality of life (QOL) after radical prostatectomy, external beam radiotherapy, and brachytherapy vs active surveillance. Design, Setting, and Participants Population-based prospective cohort of 1141 men (57% participation among eligible men) with newly diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry. Median time from diagnosis to enrollment was 5 weeks, and all men were enrolled with written informed consent prior to treatment. Final follow-up date for current analysis was September 9, 2015. Exposures Treatment with radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance. Main Outcomes and Measures Quality of life using the validated instrument Prostate Cancer Symptom Indices was assessed at baseline (pretreatment) and 3, 12, and 24 months after treatment. The instrument contains 4 domains—sexual dysfunction, urinary obstruction and irritation, urinary incontinence, and bowel problems—each scored from 0 (no dysfunction) to 100 (maximum dysfunction). Propensity-weighted mean domain scores were compared between each treatment group vs active surveillance at each time point. Results Of 1141 enrolled men, 314 pursued active surveillance (27.5%), 469 radical prostatectomy (41.1%), 249 external beam radiotherapy (21.8%), and 109 brachytherapy (9.6%). After propensity weighting, median age was 66 to 67 years across groups, and 77% to 80% of participants were white. Across groups, propensity-weighted mean baseline scores were 41.8 to 46.4 for sexual dysfunction, 20.8 to 22.8 for urinary obstruction and irritation, 9.7 to 10.5 for urinary incontinence, and 5.7 to 6.1 for bowel problems. Compared with active surveillance, mean sexual dysfunction scores worsened by 3 months for patients who received radical prostatectomy (36.2 [95% CI, 30.4-42.0]), external beam radiotherapy (13.9 [95% CI, 6.7-21.2]), and brachytherapy (17.1 [95% CI, 7.8-26.6]). Compared with active surveillance at 3 months, worsened urinary incontinence was associated with radical prostatectomy (33.6 [95% CI, 27.8-39.2]); acute worsening of urinary obstruction and irritation with external beam radiotherapy (11.7 [95% CI, 8.7-14.8]) and brachytherapy (20.5 [95% CI, 15.1-25.9]); and worsened bowel symptoms with external beam radiotherapy (4.9 [95% CI, 2.4-7.4]). By 24 months, mean scores between treatment groups vs active surveillance were not significantly different in most domains. Conclusions and Relevance In this cohort of men with localized prostate cancer, each treatment strategy was associated with distinct patterns of adverse effects over 2 years. These findings can be used to promote treatment decisions that incorporate individual preferences.

Translating research into evidence-based practice: the National Cancer Institute Community Clinical Oncology Program.

The recent rapid acceleration of basic science is reshaping both our clinical research system and our healthcare delivery system. The pace and growing volume of medical discoveries are yielding exciting new opportunities, yet we continue to face old challenges to maintain research progress and effectively translate research into practice. The National Institutes of Health and individual government programs increasingly are emphasizing research agendas that involve evidence development, comparative‐effectiveness research among heterogeneous populations, translational research, and accelerating the translation of research into evidence‐based practice as well as building successful research networks to support these efforts. For more than 25 years, the National Cancer Institute Community Clinical Oncology Program has successfully extended research into the community and facilitated the translation of research into evidence‐based practice. By describing its keys to success, this article provides practical guidance to cancer‐focused, provider‐based research networks as well as those in other disciplines. Cancer 2010.

Stage Migration, Selection Bias, and Survival Associated With the Adoption of Positron Emission Tomography Among Medicare Beneficiaries With Non–Small-Cell Lung Cancer, 1998-2003

PURPOSE Previous studies have linked the use of positron emission tomography (PET) with improved outcomes among patients with non-small-cell lung cancer (NSCLC). However, this association may be confounded by PET-induced stage migration and selection bias. We examined the association between PET use and overall survival among Medicare beneficiaries with NSCLC. PATIENTS AND METHODS Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) -Medicare data was used to characterize changes in overall survival, stage-specific survival, and stage distribution among Medicare beneficiaries with NSCLC between 1998 and 2003. RESULTS A total of 97,007 patients with NSCLC diagnosed between 1998 and 2003 met the study criteria. Two-year and 4-year survival remained unchanged, despite widespread adoption of PET. The proportion of patients staged with advanced disease increased from 44% to 50%. Upstaging of disease was accompanied by stage-specific improved survival, with 2-year survival of stage IV disease increasing from 8% to 11% between 1998 and 2003. PET was more likely to be administered to patients with less advanced disease (stages I through IIIA) and greater overall survival. CONCLUSION Overall survival among Medicare beneficiaries with NSCLC was unchanged between 1998 and 2003, despite widespread adoption of PET. The association between PET use and increased survival likely reflects an artifact of selection bias and consequent stage migration.

Racial differences in PSA screening interval and stage at diagnosis.

ObjectivesThis study examined PSA screening interval of black and white men aged 65 or older and its association with prostate cancer stage at diagnosis.MethodsSEER-Medicare data were examined for 18,067 black and white men diagnosed with prostate cancer between 1994 and 2002. Logistic regression was used to assess the association between race, PSA screening interval, and stage at diagnosis. Analysis also controlled for age, marital status, comorbidity, diagnosis year, geographic region, income, and receipt of surgery.ResultsCompared to whites, blacks diagnosed with prostate cancer were more likely to have had a longer PSA screening interval prior to diagnosis, including a greater likelihood of no pre-diagnosis use of PSA screening. Controlling for PSA screening interval was associated with a reduction in blacks’ relative odds of being diagnosed with advanced (stage III or IV) prostate cancer, to a point that the stage at diagnosis was not statistically different from that of whites (OR=1.12, 95% CI=0.98–1.29). Longer intra-PSA intervals were systematically associated with greater odds of diagnosis with advanced disease.ConclusionsMore frequent or systematic PSA screening may be a pathway to reducing racial differences in prostate cancer stage at diagnosis, and, by extension, mortality.

Race, healthcare access and physician trust among prostate cancer patients

ObjectiveTo study the effect of healthcare access and other characteristics on physician trust among black and white prostate cancer patients.MethodsA three-timepoint follow-up telephone survey after cancer diagnosis was conducted. This study analyzed data on 474 patients and their 1,320 interviews over three time periods.ResultsAmong other subpopulations, black patients who delayed seeking care had physician trust levels that were far lower than that of both Caucasians as well as that of the black patients overall. Black patients had greater variability in their levels of physician trust compared to their white counterparts.ConclusionsBoth race and access are important in explaining overall lower levels and greater variability in physician trust among black prostate cancer patients. Access barriers among black patients may spill over to the clinical encounter in the form of less physician trust, potentially contributing to racial disparities in treatment received and subsequent outcomes. Policy efforts to address the racial disparities in prostate cancer should prioritize improving healthcare access among minority groups.