Faculty Publications

Background: The National Comprehensive Cancer Network (NCCN) Outcomes Database was created to assess concordance to evidence- and consensus-based guidelines and to measure adherence to quality measures on an ongoing basis. The Colorectal Cancer Database began in 2005 as a collaboration among 8 NCCN centers. Methods: Newly diagnosed colon and rectal cancer patients presenting to 1 of 8 NCCN centers between September 1, 2005, and May 21, 2008, were eligible for analysis of concordance with NCCN treatment guidelines for colorectal cancer and with a set of quality metrics jointly developed by ASCO and NCCN in 2007. Adherence rates were determined for each metric. Center-specific rates were benchmarked against mean concordance rates for all participating centers. Results: A total of 3443 patients were evaluable. Mean concordance rates with NCCN colorectal cancer guidelines and ASCO/NCCN quality measures were generally high (>= 90%). However, relatively low mean concordance rates were noted for adjuvant chemotherapy treatment recommendations within 9 months of diagnosis of stage II to III rectal cancer (81%), and neoadjuvant chemoradiation in clinical T4 rectal primaries (83%). These low rates of concordance seemed to be consistent across centers. Conclusions: Adherence to guidelines and quality measures is generally high at institutions participating in the NCCN colorectal cancer database. Lack of documentation, patient refusal, delayed treatment initiation, and lack of consensus about whether treatment was essential were the primary reasons for nonconcordance. Measurement of concordance and the reasons for nonconcordance enable participating centers to understand and improve their care delivery systems. (JNCCN 2009;7:895-904)

BACKGROUND: Since 1996, 6 new drugs have been introduced for the treatment of metastatic colorectal cancer. Although they are promising, these drugs frequently are given in the palliative and are much more expensive than older treatments. The objective of the current study was to measure the cost implications of treatment with sequential regimens that include chemotherapy and/or monoclonal antibodies. METHODS: A Markov model was used to evaluate a hypothetical cohort of 1000 patients with newly diagnosed, metastatic colorectal cancer. Patients supposedly received up to 3 lines of treatment before supportive care and subsequent death. Data were obtained from published, multicenter phase 2 and randomized phase 3 clinical trials. Sensitivity analyses were conducted on the efficacy, toxicity, and cost. RESULTS: Using drug costs alone, treatment that included new chemotherapeutic agents increased survival at an incremental cost-effectiveness ratio (ICER) of $100,000 per discounted life-year (DLY). The addition of monoclonal antibodies improved survival at an ICER of >$170,000 per DLY. The results were most sensitive to changes in the initial regimen. Even with significant improvements in clinical characteristics (efficacy and toxicity), treatment with the most effective regimens still had very high ICERs. CONCLUSIONS: Treatment of metastatic colorectal cancer with the most effective regimens came at very high incremental costs. The authors concluded that cost-effectiveness analyses should be a routine component of the drug-development process, so that physicians and patients are informed appropriately regarding the value of new innovations.

Purpose: We determined whether a relationship exists between primary tumor size and histopathological features in cases of localized renal cancer. Materials and Methods: SEER data were used to create a cohort of patients who were diagnosed with localized node negative renal masses from 1988 to 2004. Nuclear grade was divided into low and high grade groups. We used a multinomial logistic model to predict the probability of nuclear grade and histological subtype with increasing primary tumor size. Results: SEER data showed that 19,932 patients with localized renal masses were evaluated. The overall nuclear grade distribution was 80% and 20% for low and high grade tumors, respectively. A multinomial logistic model revealed that the probability of a high grade tumor increased with size. For each I cm increase in size of a primary localized renal cell carcinoma the odds of high grade disease increased by 13% (OR 1.13, p <0.001). Multinomial models also predicted that the odds of papillary vs clear cell renal cell carcinoma decreased with tumor size. Conversely the odds of chromophobe vs clear cell renal cell carcinoma increased with increasing tumor size. Conclusions: Most localized node negative renal cell carcinomas are low grade. Although the probability of a high grade tumor increases with size, almost 85% of renal cell carcinomas smaller than 4 cm and 70% of localized renal cell carcinomas larger than 7 cm demonstrate low nuclear grade. The probability of detecting particular histological subtypes also varies with increasing tumor size. These data suggest that many localized renal tumors can grow large locally without acquiring metastatic potential.

Purpose: Recent data demonstrate that age may be a significant independent prognostic variable following treatment for renal cell carcinoma. We analyzed data from the SEER (Surveillance., Epidemiology and End Results) database to evaluate the relative survival of patients treated surgically for localized renal cell carcinoma as related to tumor size and patient age. Materials and Methods: Patients in the SEER database with localized renal cell carcinoma were stratified into cohorts by age and tumor size. Three and 5-year relative survival, the ratio of observed survival in the cancer population to the expected survival of an age, sex and race matched cancer-free population, was calculated with SEER-Stat. Brown's method was used for hypothesis testing. Results: A total of 8,578 patients with surgically treated, localized renal cell carcinoma were identified. While 3 and 5-year survival for patients with small (less than 4 cm) renal cell carcinoma was no different from that of matched cancer-free controls, patients treated for large (greater than 7 cm) localized renal cell carcinoma experienced decreased 5-year relative survival across all age groups. Therefore, age was not a significant predictor of relative survival for patients with small (less than 4 (cm) or large (greater than 7 cm) tumors. However, a statistically significant trend toward lower relative survival with increasing age was demonstrated in patients with medium size tumors (4 to 7 cm). Hypothesis testing confirmed these findings. Conclusions: These data suggest that relative survival is high in patients with tumors less than 4 cm and lower in patients with tumors larger than 7 cm regardless of age. However, increasing age may be related to worse outcomes in patients with tumors 4 to 7 cm. The cause of this observation warrants further investigation.

This study investigates differences in the effects of comorbidities on survival in Medicare beneficiaries with prostate cancer. Medicare data were used to assemble a cohort of 65- to 76-year-old Black (n = 6,402) and White (n = 47,458) men with incident localized prostate cancer in 1999 who survived >= 1 year postdiagnosis. Comorbidities were more prevalent among Blacks than among Whites. For both races, greater comorbidity was associated with decreasing survival rates; however, the effect among Blacks was smaller than in Whites. After adjusting for age, socioeconomic status, and community characteristics, the association between increasing comorbidities and survival remained weaker for Blacks than for Whites, and racial disparity in survival decreased with increasing number of comorbidities. Differential effects of comorbidities on survival were also evident when examining different classes of comorbid conditions. Adjusting for treatment had little impact on these results, despite variation in the racial difference in receipt of prostatectomy with differing comorbidity levels.

BACKGROUND: Since 1996, 6 new drugs have been introduced for the treatment of metastatic colorectal cancer. Although they are promising, these drugs frequently are given in the palliative and are much more expensive than older treatments. The objective of the current study was to measure the cost implications of treatment with sequential regimens that include chemotherapy and/or monoclonal antibodies. METHODS: A Markov model was used to evaluate a hypothetical cohort of 1000 patients with newly diagnosed, metastatic colorectal cancer. Patients supposedly received up to 3 lines of treatment before supportive care and subsequent death. Data were obtained from published, multicenter phase 2 and randomized phase 3 clinical trials. Sensitivity analyses were conducted on the efficacy, toxicity, and cost. RESULTS: Using drug costs alone, treatment that included new chemotherapeutic agents increased survival at an incremental cost-effectiveness ratio (ICER) of $100,000 per discounted life-year (DLY). The addition of monoclonal antibodies improved survival at an ICER of >$170,000 per DLY. The results were most sensitive to changes in the initial regimen. Even with significant improvements in clinical characteristics (efficacy and toxicity), treatment with the most effective regimens still had very high ICERs. CONCLUSIONS: Treatment of metastatic colorectal cancer with the most effective regimens came at very high incremental costs. The authors concluded that cost-effectiveness analyses should be a routine component of the drug-development process, so that physicians and patients are informed appropriately regarding the value of new innovations, Cancer 2009;115:2081-91. (C) 2009 American Cancer Society.

Objectives: The natural history and growth rates of untreated solid enhancing renal tumors is being defined through active surveillance series. Serial radiographic evaluation of patients who are not surgical candidates or refuse surgical treatment provides an opportunity to characterize the growth of untreated enhancing renal tumors. Here we evaluate factors that may help predict radiographic growth during observation. Materials and methods: We reviewed our renal cancer database for enhancing renal masses that were radiographically observed for a period of at least 12 months. Variables examined included patient age, gender, lesion size on presentation, radiographic tumor characteristics, duration of active surveillance linear growth rate, surgical pathology, development of new renal tumors, and stage progression. Results: One hundred nine patients with 124 sporadic enhancing renal tumors were identified undergoing a period of active surveillance of at least 12 months. Median patient age was 73 years (mean 69.8. range 35-87)-72% (78/109) of patients were males. Median duration of active surveillance was 26 months (mean 33.4, range 12-156). Multifocal disease was present in 9% (10/109) of patients on presentation, accounting for 20% (25/124) of all tumors. Tumor size on presentation was a median of 2.0 cm (mean 2.61, range 0.4-12.0). Overall median tumor growth rate was 0.21 cm/y (mean 0.28. range 1.4-2.47). Observed linear growth rates were independent of patient age, gender, tumor size on presentation. multifocality, and radiographic characteristics (solid versus cystic), P > 0.05. Of the patients initiating a period of active surveillance 36% (39/109) eventually underwent definitive therapy. Malignant pathology was present in 90% (35/39) of patients 0 undergoing treatment. In patients continuing active Surveillance [64% (70/109)], 2.9% (2/70) developed de novo renal lesions and 1.4% (1/70) developed metastatic disease. Conclusions: Currently, no clinical predictors Of tumor growth or disease progression have been identified, although. the risk of developing progressive disease over the short term appears low. Clinical and molecular markers of disease progression are needed prior to offering active surveillance to otherwise acceptable surgical candidates. (C) 2008 Elsevier Inc. All rights reserved.

Purpose To describe the frequency of chemotherapy use for hormone receptor (HR)-positive, lymph node (LN)-negative breast cancer from 1997 to 2004 at eight National Comprehensive Cancer Network institutions, to explore whether chemotherapy use varied over time and between institutions, and to identify factors associated with the decision to forego chemotherapy. Patients and Methods Among women younger than age 70 years with HR-positive, LN-negative breast cancer measuring more than 1 cm, we analyzed the frequency of chemotherapy use on a yearly basis. A multivariable logistic regression model assessed the relationship between receipt of chemotherapy and year of diagnosis, institution, tumor features, and patient characteristics. Interaction terms were added to the model, and stratified analyses were conducted to further explore the determinants of chemotherapy use. Results Fifty-five percent of 3,190 women received chemotherapy. Chemotherapy use was less common for patients with 1.1- to 2-cm tumors than for patients tumors greater 2 cm (47% v 87%, respectively; P < .01) and for women age 60 to 69 years versus women younger than age 50 years (24% v 76%, respectively; P < .01). On multivariable analysis, predictors independently associated with receiving chemotherapy included larger tumor size, higher grade, human epidermal growth factor receptor 2 overexpression, younger age, and institution (P <.01 for all). Institutions exhibited dramatically different rates of chemotherapy use ( from 46% to 65%) and patterns of change in chemotherapy use over time ( from a 79% relative increase to a 22% relative decrease). Conclusion Although institutions seemed to agree that not all women with HR-positive, LN-negative breast cancer need chemotherapy, there did not seem to be consensus regarding which women should get chemotherapy. Only prospective randomized controlled trials will conclusively establish which subtypes of HR-positive, LN- negative breast cancer benefit from chemotherapy.

OBJECTIVES: To review the collective experience evaluating pathologic concordance rates of sporadic bilateral synchronous renal tumors reported in the Surveillance, Epidemiology, and End Results (SEER) database and the published English literature and treated at Fox Chase Cancer Center; specifically, to analyze concordance rates of malignant versus benign disease, histologic type, tumor stage, and nuclear grade. METHODS: We reviewed the SEER database, the published English language literature, and our own institutional tumor registry to identify all cases of sporadic, synchronous localized (cT1-3N0M0) bilateral renal masses. Malignant and benign concordance rates were defined as agreement of any benign or malignant tumor type bilaterally. Histologic concordance was defined as bilateral histologic agreement. Tumors with mixed histologies were discordant unless all patterns were identical bilaterally. Nuclear grades were concordant if bilateral tumors were either "high" grade or "low" grade. RESULTS: The malignant concordance rate in the SEER data was 99% (273 of 274), and benign concordance was 0 (0 of 1). In the published literature and Fox Chase Cancer Center series, malignant concordance rates ranged from 84% to 95%, whereas benign concordance ranged from 39% to 67%. The SEER data revealed a histologic concordance rate of 93% (256 of 274), and nuclear grade concordance was 85% (88 of 103). CONCLUSIONS: These data demonstrate that in cases of bilateral sporadic localized synchronous renal masses, a diagnosis of ipsilateral renal cell carcinoma is associated with contralateral renal cell carcinoma in the vast majority of patients, whereas ipsilateral benign pathology is associated with contralateral benign disease at a substantially lower rate. Histologic concordance is similarly high, meaning most cases of clear cell or papillary tumors ipsilaterally are concordant in the contralateral kidney. Concordance rates of nuclear grade were slightly lower. These data are important when counseling and managing patients with bilateral synchronous sporadic renal tumors.

New treatment options provide hope for patients with localized and advanced cancer. However, these advances are associated with cost, both in terms of treatment-related expenditures and effects on quality of life. It is important that patients, physicians, insurers, and policymakers understand the relationship between costs and outcomes of new cancer treatments. Various methods of cost analysis can provide a structured manner to assess cost. Cost-effectiveness analysis (CEA) compares the cost of the intervention with the effect, resulting in a cost per effect (eg, cost per year of life gained) that can be compared across interventions. In this article, we review three recent CEAs in the oncology literature, including chemoprevention in breast cancer, adjuvant endocrine therapy in early-stage breast cancer, and salvage chemotherapy in advanced ovarian cancer. The important elements of CEA, including the recommendations of the US Public Health Service Panel on Cost Effectiveness in Health and Medicine as they relate to cancer treatments, are discussed. Many well-done CEAs in cancer treatment have been performed during the last decade. As with clinical trials, the rigor and methods of the analysis are critical to the reliability of the results. Therapies with high cost and small incremental improvement in survival and/or quality of life may find it difficult to meet the societal thresholds for what is considered cost effective. CEA is a method to assess the cost and effect of cancer treatments, providing important insights into the best use (ie, obtaining the most value for) of health care expenditures. As the literature indicates, one must be cognizant of the fact that there can be extraordinary costs associated with some newer cancer therapies that provide small incremental clinical benefit. Better understanding of the cancer economic literature can help lead to an informed dialogue on the health policy implications of resource allocation in cancer care.

Purpose: We compared how men with incident prostate cancer were staged before and after the 1995 publication of National Comprehensive Cancer Network, American Urological Association and American College of Radiology staging guidelines, and determined whether there were racial differences in the staging evaluation. Materials and Methods: We performed a retrospective cohort study of the use of bone scan and pelvic imaging (pelvic computerized tomography or magnetic resonance imaging) in 96,986 men with incident prostate cancer from 1991 to 1994 compared to 1995 to 1999 from Surveillance, Epidemiology and End Results-Medicare linked data files. Results: During 1991 to 1994 bone scan was done in 83.1% and 73.7% of men who would and would not have met guideline criteria for staging, respectively. From 1995 to 1999 bone scan use decreased slightly in men who met guideline criteria (74.4%) but it decreased substantially in men who did not meet guideline criteria (55.2%). Between 1991 to 1994 and 1995 to 1999 rates of pelvic imaging increased for men who did and decreased for men who did not meet guideline criteria for staging (45.5% to 57.2% and 48.4% to 41.5%, respectively). On multivariate analysis in men who did not meet guideline criteria there was no change in the association between the use of staging tests and race from 1991 to 1994, to 1995 to 1999. However, of men who met guideline criteria for staging black men were less likely to undergo bone scan and less likely to undergo pelvic imaging than white men diagnosed in 1991 to 1994 but this racial difference was not seen during 1995 to 1999. Conclusions: Using a population based cohort this study reveals a decrease in racial disparity and an increase in evidence based use of staging tests in men with incident prostate cancer in the period after the publication of National Comprehensive Cancer Network, American Urological Association and American College of Radiology guidelines.

CONTEXT: Prostate-specific antigen screening has led to an increase in the diagnosis and treatment of localized prostate cancer. However, the role of active treatment of low- and intermediate-risk disease in elderly men is controversial. OBJECTIVE: To estimate the association between treatment (with radiation therapy or radical prostatectomy) compared with observation and overall survival in men with low- and intermediate-risk prostate cancer. DESIGN AND SETTING: Observational US cohort from Surveillance, Epidemiology, and End Results Medicare data. PATIENTS: At total of 44,630 men aged 65 to 80 years who were diagnosed between 1991 and 1999 with organ-confined, well- or moderately differentiated prostate cancer and who had survived more than a year past diagnosis. Patients were followed up until death or study end (December 31, 2002). Patients were classified as having received treatment (n=32,022) if they had claims for radical prostatectomy or radiation therapy during the first 6 months after diagnosis. They were classified as having received observation (n=12,608) if they did not have claims for radical prostatectomy, radiation, or hormonal therapy. Patients who received only hormonal therapy were excluded. MAIN OUTCOME MEASURE: Overall survival. RESULTS: At the end of the 12-year study period, 4663 men (37%) in the observational group and 7639 men (23.8%) in the treatment group had died. The treatment group had longer 5- and 10-year survival than the observation group. After using propensity scores to adjust for potential confounders (tumor characteristics, demographics, and comorbidities), there was a statistically significant survival advantage associated with treatment (hazard ratio, 0.69; 95% confidence interval, 0.66-0.72). A benefit associated with treatment was seen in all subgroups examined, including older men (aged 75-80 years at diagnosis), black men, and men with low-risk disease. CONCLUSIONS: This study suggests a survival advantage is associated with active treatment for low- and intermediate-risk prostate cancer in elderly men aged 65 to 80 years. Because observational data cannot completely adjust for potential selection bias and confounding, these results must be validated in randomized controlled trials of alternative management strategies in elderly men with localized prostate cancer.