A B S T R A C T PurposeTo determine whether higher physical activity after prostate cancer (PCa) diagnosis decreases risk of overall and PCa-specific death. Patients and MethodsWe evaluated physical activity in relation to overall and PCa mortality among 2,705 men in the Health Professionals Follow-Up Study diagnosed with nonmetastatic PCa observed from 1990 to 2008. Proportional hazards models were used to evaluate physical activity and time to overall and PCa-specific death. ResultsAmong men who lived at least 4 years after their postdiagnosis physical activity assessment, we documented 548 deaths, 20% of which were a result of PCa. In multivariable analysis, men who were physically active had lower risk of all-cause mortality (P trend Ͻ .001) and PCa mortality (P trend ϭ .04). Both nonvigorous activity and vigorous activity were associated with significantly lower overall mortality. Those who walked Ն 90 minutes per week at a normal to very brisk pace had a 46% lower risk of all-cause mortality (hazard ratio [HR] 0.54; 95% CI, 0.41 to 0.71) compared with shorter durations at an easy walking pace. Men with Ն 3 hours per week of vigorous activity had a 49% lower risk of all-cause mortality (HR, 0.51; 95% CI, 0.36 to 0.72). For PCa-specific mortality, brisk walking at longer durations was suggestively inverse but not statistically significant. Men with Ն 3 hours per week of vigorous activity had a 61% lower risk of PCa death (HR, 0.39, 95% CI, 0.18 to 0.84; P ϭ .03) compared with men with less than 1 hour per week of vigorous activity. Men exercising vigorously before and after diagnosis had the lowest risk. ConclusionIn men with PCa, physical activity was associated with lower overall mortality and PCa mortality. A modest amount of vigorous activity such as biking, tennis, jogging, or swimming for Ն 3 hours a week may substantially improve PCa-specific survival. J Clin

Context Smoking is associated with an increased risk of total and cause-specific death, but the rate of mortality risk reduction after quitting compared with continuing to smoke is uncertain. There is inadequate or insufficient evidence to infer the presence or absence of a causal relationship between smoking and ovarian cancer and colorectal cancer. Objective To assess the relationship between cigarette smoking and smoking cessation on total and cause-specific mortality in women. Design, Setting, and Participants Prospective observational study of 104 519 female participants in the Nurses' Health Study with follow-up from 1980 to 2004. Main Outcome Measure Hazard ratios (HRs) for total mortality, further categorized into vascular and respiratory diseases, lung cancer, other cancers, and other causes. Results A total of 12 483 deaths occurred in this cohort, 4485 (35.9%) among never smokers, 3602 (28.9%) among current smokers, and 4396 (35.2%) among past smokers. Compared with never smokers, current smokers had an increased risk of total mortality (HR, 2.81; 95% confidence interval [CI], 2.68-2.95) and all major cause-specific mortality. The HR for cancers classified by the 2004 surgeon general's report to be smoking-related was 7.25 (95% CI, 6.43-8.18) and 1.58 (95% CI, 1.45-1.73) for other cancers. Compared with never smokers, the HR for colorectal cancer was 1.63 (95% CI, 1.29-2.05) for current smokers and 1.23 (95% CI, 1.02-1.49) for former smokers. A significant association was not observed for ovarian cancer. Significant trends were observed for earlier age at initiation of smoking for total mortality (P=.003), respiratory disease mortality (P=.001), and all smoking-related cancer mortality (P=.001). The excess risk for all-cause mortality decreases to the level of a never smoker 20 years after quitting, with different time frames for risk reduction observed across outcomes. Approximately 64% of deaths among current smokers and 28% of deaths among former smokers were attributable to cigarette smoking. Conclusions Most of the excess risk of vascular mortality due to smoking in women may be eliminated rapidly upon cessation and within 20 years for lung diseases. Postponing the age of smoking initiation reduces the risk of respiratory disease, lung cancer, and other smoking-related cancer deaths but has little effect on other causespecific mortality. These data suggest that smoking is associated with an increased risk of colorectal cancer mortality but not ovarian cancer mortality.

The overall 5‐year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence‐based, cancer‐specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer‐specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta‐analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health‐related behaviors and comorbidities, long‐term sequelae and patient‐reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.

Context Studies of smoking in relation to prostate cancer mortality or recurrence in prostate cancer patients are limited, with few prostate cancer-specific outcomes. Objective To assess the relation of cigarette smoking and smoking cessation with overall, prostate cancer-specific, and CVD mortality and biochemical recurrence among men with prostate cancer. Design, Setting, and Participants Prospective observational study of 5 366 men diagnosed with prostate cancer between 1986–2006 in the Health Professionals Follow-Up Study. Main Outcome Measures Hazard ratios (HRs) for overall, prostate cancer-specific, and CVD mortality, and biochemical recurrence, defined by PSA rise. Results We documented 1,630 deaths, 524 (32%) due to prostate cancer and 416 (26%) due to CVD, and 878 biochemical recurrences. The absolute crude rates for prostate cancer-specific death for never smokers vs. current smokers were 9.6 vs. 15.3 per 1,000 person-years; for all-cause mortality the corresponding rates were 27.3 and 53.0 per 1,000 person-years. In multivariable analysis, compared with never smokers, current smokers had an increased risk of prostate cancer mortality (HR, 1.61; 95% confidence interval [CI], 1.11–2.32 and among men with clinical stage T1–T3: HR, 1.80; 95% CI, 1.04–3.12), biochemical recurrence (HR, 1.61; 95% CI, 1.16–2.22), total mortality (HR, 2.28; 95% CI, 1.87–2.80), and CVD mortality (HR, 2.13; 95% CI, 1.39–3.26). After adjusting for clinical stage and grade which are likely intermediates of the relation of smoking with prostate cancer recurrence and survival, the estimates for current smoking were as follows: prostate cancer mortality (HR, 1.38; 95% CI, 0.94–2.03 and HR, 1.41; 95% CI, 0.80–2.49); biochemical recurrence (HR, 1.47; 95% CI, 1.06–2.04). A greater number of pack-years was associated with a significantly increased risk of prostate cancer mortality but not biochemical recurrence: for current smokers of 40+ pack-years compared to never smokers: prostate cancer mortality (HR, 1.82; 95% CI, 1.03–3.20; biochemical recurrence (HR, 1.48; 95% CI, 0.88–2.48). Compared to current smokers, those who had quit smoking for 10 or more years, or who had quit for less than 10 years but smoked less than 20 pack-years, had prostate cancer mortality risks similar to never smokers: former smoker, quit 10+ years (HR, 0.60; 95% CI, 0.42–0.87); quit <10 years and <20 pack-years (HR, 0.64; 95% CI, 0.28–1.45); never smoker (HR, 0.61; 95% CI, 0.42–0.88). Conclusions Smoking at the time of prostate cancer diagnosis is associated with increased overall and CVD mortality and prostate cancer-specific mortality and recurrence. 10-year quitters have prostate cancer-specific mortality risks similar to never smokers.

Vigorous activity after diagnosis was recently reported to be inversely associated with prostate cancer-specific mortality. However, men with metastatic disease may decrease their activity due to their disease; thus a causal interpretation is uncertain. We therefore prospectively examined vigorous activity and brisk walking after diagnosis in relation to risk of prostate cancer progression, an outcome less susceptible to reverse causation, among 1,455 men diagnosed with clinically localized prostate cancer. Cox proportional hazards regression was used to examine vigorous activity, non-vigorous activity, walking duration, and walking pace after diagnosis and risk of prostate cancer progression. We observed 117 events (45 biochemical recurrences, 66 secondary treatments, 3 bone metastases, 3 prostate cancer deaths) during 2,750 person-years. Walking accounted for nearly half of all activity. Men who walked briskly for ≥3 hours/week had a 57% lower rate of progression compared to men who walked at an easy pace for <3 hours/week (hazard ratio (HR): 0.43; 95% confidence interval (CI): 0.21, 0.91; p-value: 0.03). Walking pace was associated with decreased risk of progression independent of duration (HR brisk vs. easy pace: 0.52; 95% CI: 0.29, 0.91; p-trend: 0.01). Few men engaged in vigorous activity, but there was a suggestive inverse association (HR ≥3 hours per week vs. none: 0.63; 95% CI: 0.32, 1.23; p-trend: 0.17). Walking duration and total non-vigorous activity were not associated with risk of progression independent of pace or vigorous activity respectively. Brisk walking after diagnosis may inhibit or delay prostate cancer progression among men diagnosed with clinically localized prostate cancer.

The effects of the number of cigarettes smoked per day and years since quitting smoking are different across the major types of lung cancer, which are fully appreciated at long durations of smoking and smoking cessation. Smoking prevention and cessation should continue to be the focus of public health efforts to reduce lung cancer incidence and mortality.

Identification of novel indications for commonly prescribed drugs could accelerate translation of therapies. We investigated whether any clinically-used drugs might have utility for treating prostate cancer by coupling an efficient, high-throughput laboratory-based screen and a large, prospective cohort study. In stage 1, we conducted an in vitro prostate cancer cell cytotoxicity screen of 3,187 compounds. Digoxin emerged as the leading candidate given its potency in inhibiting proliferation in vitro (mean IC50=163 nM) and common use. In stage 2, we evaluated the association between the leading candidate drug from stage 1 and prostate cancer risk in 47,884 men followed 1986–2006. Regular digoxin users (versus nonusers: RR=0.76, 95% CI 0.61–0.95), especially users for ≥10 years (RR=0.54, 95% CI 0.37–0.79, P-trend<0.001), had a lower prostate cancer risk. Digoxin was highly potent in inhibiting prostate cancer cell growth in vitro and its use was associated with a 25% lower prostate cancer risk.

Background Prostate cancer (PCa) mortality rates are lower in the Mediterranean countries compared with northern Europe. Although specific components of the Mediterranean diet (Med-Diet) may influence PCa risk, few studies have assessed the traditional Med-Diet pattern with the risk of incident advanced or lethal PCa or with disease progression among men diagnosed with nonmetastatic PCa. Objective To determine whether the traditional Med-Diet pattern is associated with risk of incident advanced or lethal PCa and with PCa-specific and overall mortality among men with PCa. Design, setting, and participants We prospectively followed 47 867 men in the Health Professionals Follow-up Study followed from 1986 to 2010. The case-only analysis included 4538 men diagnosed with nonmetastatic PCa, followed from diagnosis to lethal outcome or to January 2010. Outcome measurements and statistical analysis We used Cox proportional hazards models to examine traditional and alternative Med-Diet scores in relation to PCa incidence outcomes (advanced and lethal disease). In a case-only survival analysis, we examined postdiagnostic Med-Diet and risk of lethal (metastases or PCa death) and fatal PCa as well as overall mortality among men diagnosed with nonmetastatic disease. Results and limitations Between 1986 and 2010, 6220 PCa cases were confirmed. The Med-Diet was not associated with risk of advanced or lethal PCa. In the case-only analysis, there was no association between the Med-Diet after diagnosis and risk of lethal or fatal PCa. However, there was a 22% lower risk of overall mortality (hazard ratio: 0.78; 95% confidence interval, 0.67–0.90; ptrend = 0.0007) among men with greater adherence to the Med-Diet after PCa diagnosis. We found similar associations for the alternative score. Conclusions A higher Med-Diet score was not associated with risk of advanced PCa or disease progression. Greater adherence to the Med-Diet after diagnosis of nonmetastatic PCa was associated with lower overall mortality.