Sign and symptom of prostate cancer

Study objectives: Numerous studies indicate that smoking is associated with poorer outcomes in patients with cancer. The aim of this study was to determine whether smoking independently predicts survival in patients with lung cancer or whether an existent effect is mediated through comorbidity and/or treatment.

Design and setting: Cox proportional hazards analysis was used to study a cohort of 1,155 patients with lung cancer diagnosed at the Henry Ford Health System between 1995 and 1998, inclusive.

Results: Adjusted for the baseline covariates, age, gender, illicit drug use, adverse symptoms, histology, and stage, the hazard ratio (HR) for smoking (current vs former/never) was 1.37 (95% confidence interval [CI], 1.18 to 1.59; p < 0.001). Adjusted for the baseline covariates and for 18 deleterious comorbidities, the HR for smoking was 1.38 (95% CI, 1.18 to 1.60; p < 0.001), indicating that the hazardous effect of smoking was not mediated through comorbidity. Current smoking was inversely associated with treatment (any surgery and/or chemotherapy and/or radiation therapy vs none) ]odds ratio, 0.73; 95% CI, 0.55 to 0.98 (p = 0.03)]. Adjusted for baseline covariates, comorbidities and treatment, the HR for current smoker vs former/never was 1.26 (95% CI, 1.08 to 1.47; p = 0.003), a decline of 30.7% explained by treatment (HR for any treatment vs none, 0.40; 95% CI, 0.33 to 0.48; p < 0.001).

Conclusions: Current smoking at diagnosis is an important independent predictor of shortened lung cancer survival. That this effect was not explained by sociodemographic/exposure factors, adverse symptoms, histology, stage, comorbidity, and treatment suggests that it may be mediated through direct biological effects.

Key words: comorbidity; lung neoplasm: smoking; survival; symptoms: treatment

Abbreviations: BAC = bronchioloalveolar carcinoma: BGMHI = block group median household income: CHF = congestive heart failure: CI = confidence interval; HR = hazard ratio; NOS = not otherwise specified; OR odds ratio: PY = pack-years smoked; SCLC = small cell lung cancer; SES = socioeconomic status; SqCC = squamous cell carcinoma

**********

Smoking has been associated with decreased surrival following diagnosis with a variety of cancers, including head and neck, (1,2) kidney, (3-5) prostate, (6-10) colorectal, (11) breast, (8,12-16) and vulvar (17) cancers, and leukemia (18) and malignant melanoma. (19, 20) Studies have found that in patients with lung cancer, smoking is associated with cancer recurrence, lung cancer-specific and all-causes mortality-, as well as with strong predictors of survival, such as weight loss. (21-39) An association between smoking and lung cancer survival was not observed in all studies. (40-47)

Smoking is associated with many factors that may contribute to poorer cancer survival: lower socioeconomic status (SES), (48-49) poorer nutrition, (50-52) comorbidity, (53) impaired immune function, (54-58) and an increased mutation burden that could lead to accelerated carcinogenesis and progression. (38,59-62) Of these, comorbidity may be one of the most important determinants, as smoking is strongly associated with numerous serious diseases, in addition to lung cancer. The US Surgeon General concluded that cigarette smoking accounts for 82% of COPD deaths, 21% of coronary heart disease deaths, and 18% of deaths from stroke. (63) Cigarette smoking is also associated with hypertension, atherosclerosis, aortic aneurysm, peripheral vascular diseases, pulmonary tuberculosis, pneumonia, and asthma, (64) and with cancers of the larynx, mouth, esophagus, bladder, pancreas, kidney, cervix, and possibly cancers of the colon and liver, and acute myeloid leukemia.65 Thus, patients with lung cancer and a history of heavy smoking or ongoing smoking are at risk of death from a spectrum of smoking-associated diseases. Although it is a common perception that almost all patients with lung cancer die specifically from lung cancer, this is not necessarily the case. Several studies (25,38,44,66) have found that approximately 20 to 40% of patients with nonmetastatic lung cancer died without evidence of cancer progression. Thus, the association between smoking and shortened survival, at least in nonmetastatic lung cancer, may be caused by smoking-related comorbidities.

In addition, smokers may have shorter survivals because they receive less aggressive or complete treatment, possibly because smoking is associated with lower SES, (67) which might impede smokers from seeking out and/or obtaining optimal treatment, or because smoking has led to impaired pulmonary function or comorbidity that precludes preferred therapies. The aim of the current study is to determine whether tobacco smoking predicts survival independently of important prognostic factors and to determine whether survival effects are mediated through comorbidity and/or treatment.

MATERIALS AND METHODS

A historical cohort study was carried out in the Henry Ford Health System to evaluate the impact of comorbidity, smoking, and other factors on the survival of patients with lung cancer. Study subjects, identified through the Josephine Ford Cancer Center Tumor Registry, had primary bronchogenic lung cancer diagnosed between January 1, 1995, and December 31, 1998, and received their principal care at the Henry Ford Health System. The study was limited to black and white patients because all other race/ethnic groups combined accounted fur only 1% of patients. The study received Institutional Review Board approval

Sociodemographic, exposure, clinicopathologic, treatment, and survival data were collected by abstraction of electronic medical records and from the Josephine Ford Cancer Center Tumor Registry. Sociodemographic data included age, gender, race/ ethnicity, SES, and married status. SES was estimated using block group median household income (BGMHI) derived from patient address at diagnosis and 1990 US census data.

Smoking data included pack-years smoked (PY) [the average number of packages of cigarettes smoked per day multiplied by the number of years smoked]; smoking status was defined as never smoker, former smoker, current smoker, and quit time in former smokers. Smokers who claimed to have quit in the 4 weeks prior to diagnosis were classified as current smokers, as their ability to sustain a prolonged abstinence from smoking was in question.

Clinicopathologic data included comorbidity, tumor histopathology, and stage. Data on 56 categories of comorbidity were collected from all available computerized medical records from the period of first suspicion or symptom/sign of lung cancer until patient assessments in all relevant departments were complete, which usually occurred within 2 to 3 months of diagnosis. The total number of comorbid conditions per individual was evaluated and is referred to as comorbidity count.

In a previous analysis of the 56 comorbidities in this study population, it was found that 18 comorbidities were independent, important predictors of reduced survival: HIV/AIDS, tuberculosis, previous metastatic cancer, thyroid/glandular (nondiabetic) disorders, electrolyte/mineral imbalance, anemia (pretreatment), blood disorders (other than primary anemia), dementia, neurologic disease, congestive heart failure (CHF), COPD, asthma, pulmonary fibrosis, liver disease, GI hemorrhage, renal disease, musculoskeletal/connective tissue disorders, and osteoporosis. (68) In addition, hoarseness, dyspnea, chest pain (nonangina), extrathoracic pain, neurologic symptoms, weight loss, fatigue/weakness, and hemoptysis were symptoms that were associated with relatively higher/advanced stage and/or reduced survival (manuscript submitted for publication). The label adverse in the text will identify these comorbidities and symptoms, respectively.

In modeling, American Joint Committee on Cancer TNM stage groups (69) were generally treated as categorical variables with five levels (I, II, III, IV, and unstaged). Six lung cancer histotypes based on the World Health Organization histologic classification system (70) were coded by indicator variables into the following categories: squamous cell carcinoma (SqCC), adenocarcinoma, bronchioloalveolar carcinoma (BAC), small cell lung cancer (SCLC), other defined histotypes pooled (including large cell and mixed types), and bronchogenic carcinoma not otherwise specified (NOS). Treatment data were analyzed as four dichotomous variables: surgery, chemotherapy, radiation therapy, and treatment (any vs none).

Statistical Methods