Prostate Cancer More Likely to Recur, Kill Men Who Smoke at Diagnosis

Men who smoke at the time of prostate cancer diagnosis have substantially increased rates of overall mortality and prostate cancer mortality and biochemical recurrence compared with men who had never smoked, according to a prospective, observational study of a large database.

Early quitting was associated with better outcomes, however, as the analysis shows that men who stopped smoking more than 10 years before diagnosis had prostate cancer mortality and recurrence risks similar to those in men who had never smoked.

Photo credit: © pmphoto/istock.com

"These results provide further support that smoking may increase risk of death from prostate cancer," the authors concluded in a report of their findings in JAMA.

Analysis of data on 5,366 men diagnosed with prostate cancer between 1986 and 2006 shows a 61% increase in prostate cancer mortality and biochemical recurrence in current smokers compared with those who had never smoked. Current smokers also had more than a twofold increase in total mortality risk and risk of mortality from cardiovascular disease (CVD).

"We weren’t surprised," said Stacey Kenfield, Sc.D., lead author of the study; previous but much smaller studies had shown the association.

"What was interesting was that the association between smoking and prostate cancer death and recurrence was exactly the same. These data taken together provide further support that smoking may lead to prostate cancer progression," Dr. Kenfield, a research associate in the department of epidemiology at Harvard School of Public Health, Boston, said in an interview.

Asked to comment, Dr. Judd W. Moul, chief of the division of urologic surgery at Duke University Medical Center, Durham, N.C., called the findings "very interesting."

"From a practical standpoint, it’s more of the same, that smoking is bad for your health. Here’s another study that smoking leads to adverse outcomes when a man is diagnosed with prostate cancer," he said.

"We see younger and younger men diagnosed with prostate cancer as a result of screening," added Dr. Moul. "If we run across a younger man, this study shows that they should quit immediately. We also need to take a more active role in men’s health issues, and help them with smoking cessation."

The researchers analyzed data from the Health Professionals Follow-Up Study, a prospective cohort study of 51,529 male health professionals in the United States who completed a questionnaire when enrolled in 1986. The participants were assessed every 2 years for 22 years until January 2008.

For the study, 5,366 men diagnosed with prostate cancer were included in the analysis based on the fact that they were free of a cancer diagnosis (except nonmelanoma skin cancer) in 1986, and that they had provided information on their smoking status before prostate cancer diagnosis.

The primary outcomes for the analysis were prostate cancer mortality and biochemical recurrence, according to the study. Secondary outcomes were total and CVD mortality. Median follow-up was 8.1 years in the mortality analysis and 3.8% in the recurrence analysis, which did not include men with metastatic disease at diagnosis.

In all, 32% (524) died due to prostate cancer and 26% (416) due to CVD. There were 878 biochemical recurrences. Other cancer was the most common other cause of death, occurring in 19.5%.

Using current smokers as the reference group, researchers found that former smokers overall did not have an increased risk of prostate cancer death and recurrence when compared to never smokers. The study then divided the participants by years since they had quit smoking and by dose as expressed in pack years (multiplying years of smoking by average number of packs smoked per day).

The analysis showed that former smokers who had quit at least 10 years prior to the diagnosis had risks similar to never-smokers – as did former smokers who had quit less than 10 years prior and had smoked less than 20 pack years. But in men who had quit less than 10 years prior to diagnosis, and had 20 or more pack years, the risks of prostate cancer mortality and recurrence were similar to these risks in current smokers.

"It makes total sense. If you smoked a lot, you should quit as soon as possible. If you smoked a lot, you won’t see a benefit for 10 years after quitting," said Dr. Kenfield.

The results also showed that compared with never-smokers, current smokers had a higher stage and grade of prostate cancer. Nearly 15% of current smokers had stage T3 or higher at the time of diagnosis, vs. 8.3% of never smokers. And 16% of current smokers had a Gleason score of 7 or more vs. 10.7% of never smokers.

The analysis also shows that current smokers made unhealthier lifestyle choices: They exercised less, drank more coffee, and had a higher intake of saturated fat and lower intake of calcium than never or former smokers. Smokers – both former and current – consumed more alcohol, but their body mass index was similar to the BMI of never smokers. 

The mortality data showed a "statistically significant difference in overall survival across smoking status," at 5 and 10 years after diagnosis, the authors wrote (JAMA 2011;305:2548-2555).

Among never smokers, 89.7% were alive 5 years after diagnosis and 74.8% at 10 years; among former smokers, survival rates were slightly lower at 86.2% and 68.2%, respectively. Among current smokers they fell to 78.8% and 54.8%, respectively.

Although some studies have suggested that smokers tend to have less PSA testing and may be diagnosed at a more advanced stage, the "differential PSA screening across strata of smoking status was unlikely to fully account for our results," wrote the authors, because the percentage of men who had at least one PSA test before their diagnosis varied little among the three groups.

The authors added that direct effect of smoking on prostate cancer progression "is biologically plausible." They proposed four hypotheses: tumor promotion through carcinogens from tobacco smoke, increased plasma levels of total and free testosterone, epigenetic effects such as aberrant methylation profiles, and "nicotine-induced angiogenesis, capillary growth, and tumor growth and proliferation."

"There are very few factors that are known to increase or decrease risk of progression of prostate cancer. My goal is to find out what’s related to the rate of prostate cancer progression and what men can do to improve their chances of survival with prostate cancer," said Dr. Kenfield.

The authors reported they had nothing to disclose.

Men who smoke at the time of prostate cancer diagnosis have substantially increased rates of overall mortality and prostate cancer mortality and biochemical recurrence compared with men who had never smoked, according to a prospective, observational study of a large database.

Early quitting was associated with better outcomes, however, as the analysis shows that men who stopped smoking more than 10 years before diagnosis had prostate cancer mortality and recurrence risks similar to those in men who had never smoked.

Photo credit: © pmphoto/istock.com

"These results provide further support that smoking may increase risk of death from prostate cancer," the authors concluded in a report of their findings in JAMA.

Analysis of data on 5,366 men diagnosed with prostate cancer between 1986 and 2006 shows a 61% increase in prostate cancer mortality and biochemical recurrence in current smokers compared with those who had never smoked. Current smokers also had more than a twofold increase in total mortality risk and risk of mortality from cardiovascular disease (CVD).

"We weren’t surprised," said Stacey Kenfield, Sc.D., lead author of the study; previous but much smaller studies had shown the association.

"What was interesting was that the association between smoking and prostate cancer death and recurrence was exactly the same. These data taken together provide further support that smoking may lead to prostate cancer progression," Dr. Kenfield, a research associate in the department of epidemiology at Harvard School of Public Health, Boston, said in an interview.

Asked to comment, Dr. Judd W. Moul, chief of the division of urologic surgery at Duke University Medical Center, Durham, N.C., called the findings "very interesting."

"From a practical standpoint, it’s more of the same, that smoking is bad for your health. Here’s another study that smoking leads to adverse outcomes when a man is diagnosed with prostate cancer," he said.

"We see younger and younger men diagnosed with prostate cancer as a result of screening," added Dr. Moul. "If we run across a younger man, this study shows that they should quit immediately. We also need to take a more active role in men’s health issues, and help them with smoking cessation."

The researchers analyzed data from the Health Professionals Follow-Up Study, a prospective cohort study of 51,529 male health professionals in the United States who completed a questionnaire when enrolled in 1986. The participants were assessed every 2 years for 22 years until January 2008.

For the study, 5,366 men diagnosed with prostate cancer were included in the analysis based on the fact that they were free of a cancer diagnosis (except nonmelanoma skin cancer) in 1986, and that they had provided information on their smoking status before prostate cancer diagnosis.

The primary outcomes for the analysis were prostate cancer mortality and biochemical recurrence, according to the study. Secondary outcomes were total and CVD mortality. Median follow-up was 8.1 years in the mortality analysis and 3.8% in the recurrence analysis, which did not include men with metastatic disease at diagnosis.

In all, 32% (524) died due to prostate cancer and 26% (416) due to CVD. There were 878 biochemical recurrences. Other cancer was the most common other cause of death, occurring in 19.5%.

Using current smokers as the reference group, researchers found that former smokers overall did not have an increased risk of prostate cancer death and recurrence when compared to never smokers. The study then divided the participants by years since they had quit smoking and by dose as expressed in pack years (multiplying years of smoking by average number of packs smoked per day).

The analysis showed that former smokers who had quit at least 10 years prior to the diagnosis had risks similar to never-smokers – as did former smokers who had quit less than 10 years prior and had smoked less than 20 pack years. But in men who had quit less than 10 years prior to diagnosis, and had 20 or more pack years, the risks of prostate cancer mortality and recurrence were similar to these risks in current smokers.

"It makes total sense. If you smoked a lot, you should quit as soon as possible. If you smoked a lot, you won’t see a benefit for 10 years after quitting," said Dr. Kenfield.

The results also showed that compared with never-smokers, current smokers had a higher stage and grade of prostate cancer. Nearly 15% of current smokers had stage T3 or higher at the time of diagnosis, vs. 8.3% of never smokers. And 16% of current smokers had a Gleason score of 7 or more vs. 10.7% of never smokers.

The analysis also shows that current smokers made unhealthier lifestyle choices: They exercised less, drank more coffee, and had a higher intake of saturated fat and lower intake of calcium than never or former smokers. Smokers – both former and current – consumed more alcohol, but their body mass index was similar to the BMI of never smokers. 

The mortality data showed a "statistically significant difference in overall survival across smoking status," at 5 and 10 years after diagnosis, the authors wrote (JAMA 2011;305:2548-2555).

Among never smokers, 89.7% were alive 5 years after diagnosis and 74.8% at 10 years; among former smokers, survival rates were slightly lower at 86.2% and 68.2%, respectively. Among current smokers they fell to 78.8% and 54.8%, respectively.

Although some studies have suggested that smokers tend to have less PSA testing and may be diagnosed at a more advanced stage, the "differential PSA screening across strata of smoking status was unlikely to fully account for our results," wrote the authors, because the percentage of men who had at least one PSA test before their diagnosis varied little among the three groups.

The authors added that direct effect of smoking on prostate cancer progression "is biologically plausible." They proposed four hypotheses: tumor promotion through carcinogens from tobacco smoke, increased plasma levels of total and free testosterone, epigenetic effects such as aberrant methylation profiles, and "nicotine-induced angiogenesis, capillary growth, and tumor growth and proliferation."

"There are very few factors that are known to increase or decrease risk of progression of prostate cancer. My goal is to find out what’s related to the rate of prostate cancer progression and what men can do to improve their chances of survival with prostate cancer," said Dr. Kenfield.

The authors reported they had nothing to disclose.

Men who smoke at the time of prostate cancer diagnosis have substantially increased rates of overall mortality and prostate cancer mortality and biochemical recurrence compared with men who had never smoked, according to a prospective, observational study of a large database.

Early quitting was associated with better outcomes, however, as the analysis shows that men who stopped smoking more than 10 years before diagnosis had prostate cancer mortality and recurrence risks similar to those in men who had never smoked.

Photo credit: © pmphoto/istock.com

"These results provide further support that smoking may increase risk of death from prostate cancer," the authors concluded in a report of their findings in JAMA.

Analysis of data on 5,366 men diagnosed with prostate cancer between 1986 and 2006 shows a 61% increase in prostate cancer mortality and biochemical recurrence in current smokers compared with those who had never smoked. Current smokers also had more than a twofold increase in total mortality risk and risk of mortality from cardiovascular disease (CVD).

"We weren’t surprised," said Stacey Kenfield, Sc.D., lead author of the study; previous but much smaller studies had shown the association.

"What was interesting was that the association between smoking and prostate cancer death and recurrence was exactly the same. These data taken together provide further support that smoking may lead to prostate cancer progression," Dr. Kenfield, a research associate in the department of epidemiology at Harvard School of Public Health, Boston, said in an interview.

Asked to comment, Dr. Judd W. Moul, chief of the division of urologic surgery at Duke University Medical Center, Durham, N.C., called the findings "very interesting."

"From a practical standpoint, it’s more of the same, that smoking is bad for your health. Here’s another study that smoking leads to adverse outcomes when a man is diagnosed with prostate cancer," he said.

"We see younger and younger men diagnosed with prostate cancer as a result of screening," added Dr. Moul. "If we run across a younger man, this study shows that they should quit immediately. We also need to take a more active role in men’s health issues, and help them with smoking cessation."

The researchers analyzed data from the Health Professionals Follow-Up Study, a prospective cohort study of 51,529 male health professionals in the United States who completed a questionnaire when enrolled in 1986. The participants were assessed every 2 years for 22 years until January 2008.

For the study, 5,366 men diagnosed with prostate cancer were included in the analysis based on the fact that they were free of a cancer diagnosis (except nonmelanoma skin cancer) in 1986, and that they had provided information on their smoking status before prostate cancer diagnosis.

The primary outcomes for the analysis were prostate cancer mortality and biochemical recurrence, according to the study. Secondary outcomes were total and CVD mortality. Median follow-up was 8.1 years in the mortality analysis and 3.8% in the recurrence analysis, which did not include men with metastatic disease at diagnosis.

In all, 32% (524) died due to prostate cancer and 26% (416) due to CVD. There were 878 biochemical recurrences. Other cancer was the most common other cause of death, occurring in 19.5%.

Using current smokers as the reference group, researchers found that former smokers overall did not have an increased risk of prostate cancer death and recurrence when compared to never smokers. The study then divided the participants by years since they had quit smoking and by dose as expressed in pack years (multiplying years of smoking by average number of packs smoked per day).

The analysis showed that former smokers who had quit at least 10 years prior to the diagnosis had risks similar to never-smokers – as did former smokers who had quit less than 10 years prior and had smoked less than 20 pack years. But in men who had quit less than 10 years prior to diagnosis, and had 20 or more pack years, the risks of prostate cancer mortality and recurrence were similar to these risks in current smokers.

"It makes total sense. If you smoked a lot, you should quit as soon as possible. If you smoked a lot, you won’t see a benefit for 10 years after quitting," said Dr. Kenfield.

The results also showed that compared with never-smokers, current smokers had a higher stage and grade of prostate cancer. Nearly 15% of current smokers had stage T3 or higher at the time of diagnosis, vs. 8.3% of never smokers. And 16% of current smokers had a Gleason score of 7 or more vs. 10.7% of never smokers.

The analysis also shows that current smokers made unhealthier lifestyle choices: They exercised less, drank more coffee, and had a higher intake of saturated fat and lower intake of calcium than never or former smokers. Smokers – both former and current – consumed more alcohol, but their body mass index was similar to the BMI of never smokers. 

The mortality data showed a "statistically significant difference in overall survival across smoking status," at 5 and 10 years after diagnosis, the authors wrote (JAMA 2011;305:2548-2555).

Among never smokers, 89.7% were alive 5 years after diagnosis and 74.8% at 10 years; among former smokers, survival rates were slightly lower at 86.2% and 68.2%, respectively. Among current smokers they fell to 78.8% and 54.8%, respectively.

Although some studies have suggested that smokers tend to have less PSA testing and may be diagnosed at a more advanced stage, the "differential PSA screening across strata of smoking status was unlikely to fully account for our results," wrote the authors, because the percentage of men who had at least one PSA test before their diagnosis varied little among the three groups.

The authors added that direct effect of smoking on prostate cancer progression "is biologically plausible." They proposed four hypotheses: tumor promotion through carcinogens from tobacco smoke, increased plasma levels of total and free testosterone, epigenetic effects such as aberrant methylation profiles, and "nicotine-induced angiogenesis, capillary growth, and tumor growth and proliferation."

"There are very few factors that are known to increase or decrease risk of progression of prostate cancer. My goal is to find out what’s related to the rate of prostate cancer progression and what men can do to improve their chances of survival with prostate cancer," said Dr. Kenfield.

The authors reported they had nothing to disclose.