Neil E. Martin

Marital Status and Survival in Patients With Cancer

PURPOSE To examine the impact of marital status on stage at diagnosis, use of definitive therapy, and cancer-specific mortality among each of the 10 leading causes of cancer-related death in the United States. METHODS We used the Surveillance, Epidemiology and End Results program to identify 1,260,898 patients diagnosed in 2004 through 2008 with lung, colorectal, breast, pancreatic, prostate, liver/intrahepatic bile duct, non-Hodgkin lymphoma, head/neck, ovarian, or esophageal cancer. We used multivariable logistic and Cox regression to analyze the 734,889 patients who had clinical and follow-up information available. RESULTS Married patients were less likely to present with metastatic disease (adjusted odds ratio [OR], 0.83; 95% CI, 0.82 to 0.84; P < .001), more likely to receive definitive therapy (adjusted OR, 1.53; 95% CI, 1.51 to 1.56; P < .001), and less likely to die as a result of their cancer after adjusting for demographics, stage, and treatment (adjusted hazard ratio, 0.80; 95% CI, 0.79 to 0.81; P < .001) than unmarried patients. These associations remained significant when each individual cancer was analyzed (P < .05 for all end points for each malignancy). The benefit associated with marriage was greater in males than females for all outcome measures analyzed (P < .001 in all cases). For prostate, breast, colorectal, esophageal, and head/neck cancers, the survival benefit associated with marriage was larger than the published survival benefit of chemotherapy. CONCLUSION Even after adjusting for known confounders, unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer. This study highlights the potentially significant impact that social support can have on cancer detection, treatment, and survival.

Defining a standard set of patient-centered outcomes for men with localized prostate cancer.

BACKGROUND Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. OBJECTIVE To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. DESIGN, SETTING, AND PARTICIPANTS We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. RESULTS AND LIMITATIONS We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. CONCLUSIONS We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. PATIENT SUMMARY Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.

Cancer-Specific Outcomes Among Young Adults Without Health Insurance

PURPOSE The Patient Protection and Affordable Care Act (ACA) will likely improve insurance coverage for most young adults, but subsets of young adults in the United States will face significant premium increases in the individual market. We examined the association between insurance status and cancer-specific outcomes among young adults. METHODS We used the SEER program to identify 39,447 patients age 20 to 40 years diagnosed with a malignant neoplasm between 2007 and 2009. The association between insurance status and stage at presentation, employment of definitive therapy, and all-cause mortality was assessed using multivariable logistic or Cox regression, as appropriate. RESULTS Patients who were uninsured were more likely to be younger, male, nonwhite, and unmarried than patients who were insured and were also more likely to be from regions of lower income, education, and population density (P < .001 in all cases). After adjustment for pertinent confounding variables, an association between insurance coverage and decreased likelihood of presentation with metastatic disease (odds ratio [OR], 0.84; 95% CI, 0.75 to 0.94; P = .003), increased receipt of definitive treatment (OR, 1.95; 95% CI, 1.52 to 2.50; P < .001), and decreased death resulting from any cause (hazard ratio, 0.77; 95% CI, 0.65 to 0.91; P = .002) was noted. CONCLUSION The improved coverage fostered by the ACA may translate into better outcomes among most young adults with cancer. Extra consideration will need to be given to ensure that patients who will face premium increases in the individual market can obtain insurance coverage under the ACA.

Incidence and Predictors of Upgrading and Up Staging among 10,000 Contemporary Patients with Low Risk Prostate Cancer

PURPOSE We determined the incidence of pathological upgrading and up staging for contemporary, clinically low risk patients, and identified predictors of having occult, advanced disease to inform the selection of patients for active surveillance. MATERIALS AND METHODS We studied 10,273 patients in the SEER database diagnosed with clinically low risk disease (cT1c/T2a, prostate specific antigen less than 10 ng/ml, Gleason 3 + 3 = 6) in 2010 to 2011 and treated with prostatectomy. The primary outcome was the incidence of upgrading to pathological Gleason score 7-10 or up staging to pathological T3-T4/N1 disease. Multivariable logistic regression of cases with complete biopsy data (5,581) identified significant predictors of upgrading or up staging, which were then used to create a risk stratification table. RESULTS At prostatectomy 44% of cases were upgraded and 9.7% were up staged. Multivariable analysis of 5,581 patients showed age, prostate specific antigen and percent positive cores (all p < 0.001) but not race were associated with occult, advanced disease. With these variables dichotomized at the median, age older than 60 years (AOR 1.39), prostate specific antigen greater than 5.0 ng/ml (AOR 1.28) and more than 25% positive cores (AOR 1.76) were significantly associated with upgrading (all p < 0.001). Similarly, age older than 60 years (AOR 1.42), prostate specific antigen greater than 5.0 ng/ml (AOR 1.44) and more than 25% positive cores (AOR 2.26) were associated with up staging (all p < 0.001). Overall 60% of 5,581 low risk cases with prostate specific antigen 7.5 to 9.9 ng/ml and more than 25% positive cores were upgraded. This study is limited by possible bias introduced by only using patients selected for prostatectomy. CONCLUSIONS Nearly half of clinically low risk patients harbor Gleason 7 or greater, or pT3 or greater disease, and should be risk stratified by prostate specific antigen and percent positive cores for consideration of further testing before deciding on active surveillance.

A Phase I Trial of the Dual Farnesyltransferase and Geranylgeranyltransferase Inhibitor L-778,123 and Radiotherapy for Locally Advanced Pancreatic Cancer

Purpose: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. Experimental Design: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. Results: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. Conclusions: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.

Outcomes in stage I testicular seminoma: A population-based study of 9193 patients

Few studies have quantified temporal patterns of cause‐specific mortality in contemporary cohorts of men with early‐stage seminoma. Given that several management strategies can be applied in these patients, each resulting in excellent long‐term survival, it is important to evaluate associated long‐term sequelae. In particular, data describing long‐term risks of cardiovascular disease (CVD) are conflicting.

Outcomes in stage i testicular seminoma

Few studies have quantified temporal patterns of cause‐specific mortality in contemporary cohorts of men with early‐stage seminoma. Given that several management strategies can be applied in these patients, each resulting in excellent long‐term survival, it is important to evaluate associated long‐term sequelae. In particular, data describing long‐term risks of cardiovascular disease (CVD) are conflicting.

Association of androgen-deprivation therapy with excess cardiac-specific mortality in men with prostate cancer.

To determine if androgen‐deprivation therapy (ADT) is associated with excess cardiac‐specific mortality (CSM) in men with prostate cancer and no cardiovascular comorbidity, coronary artery disease risk factors, or congestive heart failure (CHF) or past myocardial infarction (MI).

Getting back to equal: The influence of insurance status on racial disparities in the treatment of African American men with high-risk prostate cancer.

OBJECTIVES Treating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP. MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level > 20 ng/ml or Gleason score 8-10 or stage > cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy. RESULTS Compared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56-0.64; P < 0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27-0.54, P < 0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57-0.66, P < 0.001) among insured men. CONCLUSIONS AA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers.

Vasectomy and Risk of Aggressive Prostate Cancer: A 24-Year Follow-Up Study

PURPOSE Conflicting reports remain regarding the association between vasectomy, a common form of male contraception in the United States, and prostate cancer risk. We examined prospectively this association with extended follow-up and an emphasis on advanced and lethal disease. PATIENTS AND METHODS Among 49,405 U.S. men in the Health Professionals Follow-Up Study, age 40 to 75 years at baseline in 1986, 6,023 patients with prostate cancer were diagnosed during the follow-up to 2010, including 811 lethal cases. In total, 12,321 men (25%) had vasectomies. We used Cox proportional hazards models to estimate the relative risk (RR) and 95% CIs of total, advanced, high-grade, and lethal disease, with adjustment for a variety of possible confounders. RESULTS Vasectomy was associated with a small increased risk of prostate cancer overall (RR, 1.10; 95% CI, 1.04 to 1.17). Risk was elevated for high-grade (Gleason score 8 to 10; RR, 1.22; 95% CI, 1.03 to 1.45) and lethal disease (death or distant metastasis; RR, 1.19; 95% CI, 1.00 to 1.43). Among a subcohort of men receiving regular prostate-specific antigen screening, the association with lethal cancer was stronger (RR, 1.56; 95% CI, 1.03 to 2.36). Vasectomy was not associated with the risk of low-grade or localized disease. Additional analyses suggested that the associations were not driven by differences in sex hormone levels, sexually transmitted infections, or cancer treatment. CONCLUSION Our data support the hypothesis that vasectomy is associated with a modest increased incidence of lethal prostate cancer. The results do not appear to be due to detection bias, and confounding by infections or cancer treatment is unlikely.