ABSTRACT
BACKGROUND: The optimal timing to start androgen deprivation therapy (ADT) in prostate cancer patients with rising prostate-specific antigen (PSA) as the only sign of relapse is unknown. METHODS: We identified men with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavour (CaPSURE) study who would have been eligible (⩽ cT3aN0M0, primary radical prostatectomy or radiotherapy, PSA relapse as the only evidence of recurrence) for a randomised trial comparing 'immediate' versus 'deferred' ADT initiation. We emulated such trial by assigning patients to the 'immediate' strategy if they initiated ADT within 3 months of PSA relapse and to the 'deferred' strategy if they initiated ADT when they presented with metastasis, symptoms or a short PSA doubling time. We censored patients when they deviated from the assigned strategy and adjusted for this censoring via inverse probability weighting. RESULTS: Of 2096 eligible patients (median age 69, interquartile range 63-75 years), 88% were white, 35% had a Gleason score ⩾ 7, 69% were treated with radical prostatectomy and 31% received radiotherapy only as primary treatment. The mean time from primary treatment to PSA relapse was 37.4 (standard deviation [SD] 34.2) months. Mean follow-up from primary treatment was 91.4 (SD 48.4) months. The adjusted mortality hazard ratio for immediate versus deferred ADT was 0.91 (95% confidence interval (CI), 0.52-1.60), which would be translated into a similar 5-year survival (difference between groups: -2.0% (95% CI: -10.0 to 5.9%). CONCLUSION: Our analysis suggests that prostate cancer patients undergoing immediate ADT initiation within three months after PSA-only relapse had similar survival to those who deferred ADT initiation within 3 months after clinical progression.
Subject(s)
Adenocarcinoma/drug therapy , Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Neoplasm Recurrence, Local , Prostatic Neoplasms/drug therapy , Time-to-Treatment , Adenocarcinoma/blood , Adenocarcinoma/mortality , Aged , Disease-Free Survival , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/mortality , Survival AnalysisABSTRACT
OBJECTIVE: Insulin may play a role in prostate cancer tumorigenesis. Postprandial blood glucose and insulin responses of foods depend importantly on the carbohydrate quality and quantity, represented by glycemic index (GI), glycemic load (GL), fiber and whole-grain content, but are also influenced by intake of protein and other characteristics. The recently developed insulin index (II) quantifies the postprandial insulin secretion, also taking into account these additional characteristics. METHODS: We investigated the association between dietary GI, GL, II, fiber, and whole grains and risk of total prostate cancer (n = 5,112) and subgroups of prostate cancer as defined by stage or grade in 49,934 male participants of the Health Professionals Follow-up Study. Multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. RESULTS: Dietary GI, GL, II, or fiber was not associated with risk of total or subgroups of prostate cancer. We observed a positive association between dietary intake of whole grains and total prostate cancer (HR highest versus lowest quintile 1.13, 95% CI 1.03-1.24), which was attenuated after restriction to PSA-screened participants (HR 1.03, 95% CI 0.91-1.17). CONCLUSIONS: These results suggest that long-term exposure to a diet with a high insulin response does not affect prostate cancer incidence.
Subject(s)
Diet , Dietary Fiber/metabolism , Edible Grain/metabolism , Glycemic Index/physiology , Insulin/metabolism , Prostatic Neoplasms/metabolism , Adult , Aged , Diet Surveys , Humans , Male , Middle Aged , Risk FactorsABSTRACT
BACKGROUND: The magnitude of the link between cigarette smoking and lung cancer may vary by histological type. METHODS: We used polytomous logistic regression to evaluate whether aspects of smoking have different effects across four histological types in the Nurses' Health Study. RESULTS: From 1976 to 2002, we identified 1062 cases of lung cancer: squamous cell (n = 201), small cell (n = 236), adenocarcinoma (n = 543) and large cell carcinoma (n = 82), among 65 560 current or former smokers. Risk reduction after quitting ranged from an 8% reduction (relative risk (RR): 0.92, 95% CI 0.91 to 0.94) to a 17% reduction (RR: 0.83, 95% CI 0.80 to 0.86) per year for adenocarcinoma and small cell carcinoma, respectively, with a 9% reduction observed for large cell carcinoma and an 11% reduction observed for squamous cell carcinoma. The association of age at smoking initiation and former cigarette smoking was similar across types, while the association of smoking duration differed. The risk of adenocarcinoma increased by 6% per year of smoking, compared to 7% for large cell, 10% for squamous cell and 12% for small cell. The 6% difference between adenocarcinoma and small cell carcinoma is equivalent to a 3.2 to 9.7-fold increase in risk for 20 years of smoking. CONCLUSIONS: 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.
