Smoking Linked to Higher Prostate Cancer Mortality

Roxanne Nelson

June 22, 2011

June 22, 2011 — Patients who smoke at the time of their prostate cancer diagnosis are at higher risk for disease-specific mortality. In addition, smoking at the time of a prostate cancer diagnosis is associated with increased overall morality, death from cardiovascular disease (CVD), and prostate cancer recurrence.

The results of the study, which appear in the June 22/29 issue of the Journal of the American Medical Association, showed that even after adjustment for clinical stage and grade, current smokers had an increased risk for prostate cancer mortality (hazard ratio [HR], 1.38).

Men who were smoking at diagnosis also had a greater risk for biochemical recurrence (HR, 1.47). A higher number of pack-years smoked was associated with an increased risk for prostate cancer mortality, CVD mortality, and overall mortality, but not biochemical recurrence.

On the basis of these results, increased risk for death from prostate cancer can be added to the list of the deleterious effects of smoking. "I think that prostate cancer is now another disease that is affected by smoking," said lead author Stacey A. Kenfield, ScD, research associate in the Department of Epidemiology at the Harvard School of Public Health, Boston, Massachusetts. "We also found evidence of a reduction in risk with quitting, where former smokers' risk varied by the time since quitting and dose smoked. This further supports a relation between smoking and risk for prostate cancer."

Specifically, Dr. Kenfield told Medscape Medical News that their results showed that those who had not smoked for at least 10 years had mortality and recurrence risks similar to men who had never smoked. They also showed that those who quit smoking in the 10 years before their diagnosis but who had smoked less than 20 pack-years had mortality risks similar to men who had never smoked, whereas those who quit smoking in the 10 years before their diagnosis but who smoked 20 pack-years or more had risks similar to current smokers.

There is growing evidence to suggest that smoking increases the risk for aggressive prostate cancer and prostate-cancer-specific mortality. Therefore, said Dr. Kenfield, these results were expected, explained, and are in line with the preliminary data published for prostate-specific mortality in 1999 (Cancer Epidemiol Biomarkers Prev. 1999;8:277-282).

"However, the confidence intervals in that analysis were fairly wide because those results were based on fewer deaths," Dr. Kenfield noted.

"Our study is also in line with the much smaller studies published on smoking and prostate-cancer-specific mortality and . . . on [prostate-specific antigen] recurrence," she said. "The published mortality studies had approximately one tenth the number of prostate-specific deaths, compared with our study, but each found a similar pattern — that smoking is harmful for prostate cancer."

Dr. Kenfield and colleagues demonstrated that the risk for prostate cancer recurrence and mortality are the same: "Current smokers had a 61% increased risk of biochemical recurrence and a 61% increased risk of prostate-cancer-specific mortality."

Graham Warren, MD, PhD, agrees that the study adds value to the current understanding of the relation between prostate cancer and tobacco, primarily because of "the increased accuracy of defining tobacco use through detailed standard prospective tobacco assessment."

"As a result, this study represents a significant improvement over studies that have related tobacco use to prostate cancer through retrospective reviews," said Dr. Warren, who is assistant professor in the Department of Radiation Medicine at the Roswell Park Cancer Institute in Buffalo, New York. Dr. Warren was not involved in the study.

The data from this study demonstrate that current smokers fare considerably worse than never-smokers or smokers who quit at least 10 years before diagnosis, he told Medscape Medical News.

"These data are strengthened by the fact that current definitions of prostate cancer recurrence were utilized in the analysis," he said. "As a result, these data support a more significant role of tobacco use in the development and outcome of prostate cancer."

Higher Death Rate and Recurrence

In their study, Dr. Kenfield and colleagues evaluated the association of cigarette smoking and smoking cessation with overall prostate-cancer-specific, CVD mortality, and biochemical recurrence among prostate cancer patients.

The cohort in this prospective observational study comprised 5366 men diagnosed with prostate cancer between 1986 and 2006, and who were participants in the Health Professionals Follow-Up Study.

In this cohort, there were 1630 deaths — 524 (32%) from prostate cancer and 416 (26%) from CVD — and 878 biochemical recurrences.

The absolute crude rates were lower for never-smokers than for current smokers for prostate-cancer-specific death (9.6 vs 15.3 per 1000 person-years) and for all-cause mortality (27.3 vs 53.0 per 1000 person-years).

In multivariable models, current smokers had an increased risk of dying, compared with never-smokers, from prostate cancer (HR, 1.61), CVD (HR, 2.13), and all-cause mortality (HR, 2.28), and an increased risk for biochemical recurrence (HR, 1.61).

Even when the biochemical recurrence analysis was limited to patients who were treated with radical prostatectomy, external-beam radiation, or brachytherapy, current smokers still had a hazard ratio of 1.63.

Current smokers had disease of a higher clinical stage and grade than never-smokers (P < 0.001 for both). The authors note, for example, that 14.7% of current smokers had stage T3 disease or higher at diagnosis, compared with 8.3% of never-smokers. In addition, 16.0% of current smokers had a Gleason score of 7 or more, compared with 10.7% of never-smokers.

Smoking After Diagnosis?

Dr. Kenfield explained that they did not investigate the association between continued smoking after diagnosis and prostate-cancer-specific death, so it is not clear what affect smoking has on prognosis. "However, one of the proposed mechanisms is that nicotine can induce the formation of new blood vessels, increase capillary growth, and increase tumor growth," she said. "New blood vessels can facilitate metastasis by supplying the tumor with direct access to the vasculature, which could result in a poor prognosis."

She also emphasized that their study found that current smoking is associated with more aggressive cancers at diagnosis, including a higher clinical stage or Gleason score. "One of the key messages of these findings is to encourage men to quit smoking prior to a prostate cancer diagnosis — as soon as possible — to decrease the risk of being diagnosed with aggressive disease," she said.

Dr. Warren noted that more data are needed on patients who continue to smoke after their diagnosis. "Unfortunately, whereas this study demonstrates that prior and current tobacco use affect survival outcomes, there remains a significant knowledge gap regarding how to deal with cancer patients who smoke at the time of diagnosis," he said. "Evidence in other disease sites suggests that tobacco cessation in smokers could significantly improve cancer-specific, as well as overall, mortality."

"However, much work is needed to clarify this issue," Dr. Warren added. "Hopefully, this study will encourage clinicians to think of tobacco use and cessation as an integral part of clinical care in prostate cancer patients."

The study was funded by the National Institutes of Health. The authors have disclosed no relevant financial relationships.

JAMA. 2011;305(24):2548-2555. Abstract

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