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oxygenation and lead to increased radiation resistance
Few studies evaluated the possible influence of smoking
on PCa patients treated with medical therapy. Oefelein et al
followed 222 patients with advanced PCa treated with
hormonal manipulation. Hormone-refractory PCa was
observed in 133 patients, and death occurred in 77 cases.
The median time to hormone-refractory PCa was signifi-
cantly lower for smokers when compared with former
smokers or nonsmokers (11 mo, 23 mo, and 35 mo,
respectively; p = 0.00001). Median overall survival time on
androgen-ablative therapy was 38 mo, 47 mo, and 60 mo in
patients with current, former, or never tobacco smoking
history, respectively. Recent data from the SEARCH data-
base confirmed that active smoking was associated with
an increased risk of castration-resistant PCa (HR: 2.62;
p =: 0.21) in patients treatedwith radical prostatectomy .
3.4. Smoking as a target for prevention
Smoking is considered a major challenge to global public
health. Smoking is associated with several major benign and
malignant diseases and represents one of the most
important modifiable risk factors for human health
. Considering the possible link between smoking and
more aggressive PCa, including a suboptimal outcome after
primary treatment, it has been hypothesized that smoking
cessation by counseling or medical interventions could have
a positive effect on PCa disease outcomes. Continued
smoking after cancer diagnosis has been linked with several
adverse outcomes for cancer patients, including treatment
complications, reduced treatment efficacy or need for
increased treatment dose, increased risk of secondary
cancers, and diminished quality of life . Unfortunately,
about 10–60% of cancer patients smoke after diagnosis, with
variation depending on cancer site and time since diagnosis
. Advising patients that smoke to quit smoking after a
cancer diagnosis represents an important step in cancer
management. A recent meta-analysis suggested that even
3 min of provider advice and counseling may increase the
odds of tobacco abstinence by 30% . Physician inter-
ventions may need to be combined with higher-intensity
behavioral and pharmacologic interventions to increase
long-term cessation among cancer patients . Despite
the demonstrated efficacy of provider interventions and
counseling, only about 40% of cancer survivors report that a
provider asked them about their smoking in the last year;
although most oncology providers (60–80%) reported
advising patients to quit smoking, only 15–30% reported
providing interventions to assist their patients with
smoking cessation. It has been argued recently that
oncologists have an ethical responsibility to strongly advise
their patients to quit smoking, and the American Society of
Clinical Oncology has also urged all oncologists to integrate
tobacco cessation and control into practice . Whether or
not smoking cessation after PCa diagnosis affects outcomes
in PCa patients is unknown; however, it is reasonable to
suggest that PCa patients should quit smoking to prevent or
reverse smoking-related adverse events. This advice will at
least improve heart health and reduce the risk of
cardiovascular disease, the most common cause of male
mortality, and could eventually reduce the risk of other
concomitant cancers.
Another peculiar characteristic of smokers that could
influence PCa prevention andmanagement is that adherence
to PSA testing may be negatively associated with tobacco
smoking for various reasons, including lower socioeconomic
status . Smoking has been linked with lower risk of
screening and poor compliance with prostate biopsy
Rolison et al recently observed that nonsmokers
were 1.95 times more likely to have been screened for PCa
than smokers. Furthermore, smokers were most likely to
have been screened only once, whereas quitters and
nonsmokers were most likely to have been screened at least
three times. PSA testing in smokers could also be influenced
by changes in PSA level. Data from a nationwide population-
based sampling survey have shown an approximate 8–12%
decrease in PSA among current and former smokers. Thus,
men who have ever smoked are less likely to have an
abnormal result on PSA screening and diagnostic biopsy,
possibly resulting in fewer screen-detected PCas than those
who have never smoked However, because PSA
screening reduces PCa death by only approximately 21%,
for screening to explain the 25% increasedmortality of PCa in
smokers reported by Islami et al in their meta-analysis,
screening must be nearly universal among nonsmokers and
nearly completely absent among smokers. Furthermore, the
patterns of association between smoking and PCa death
before and after the PSA screening era were almost similar,
refuting any major influence of PSA screening on this
association As such, screening differences are unlikely
to explain all of the excess PCa mortality among smokers,
although they may contribute. Finally, PSA accuracy in
smokers and nonsmokers has never been tested.
4. Conclusions
Smoking is a major public health problem and is the leading
cause of death from cancer. Smoking is associated with
several biological factors that may influence the develop-
ment and progression of PCa. Although the exact molecular
mechanisms linking smoking and prostate carcinogenesis
remain incompletely understood, the cumulative evidence
summarized in this report strongly suggests an association
of smoking with higher PCa mortality and with worse
outcomes after treatment. Whether smoking cessation after
PCa diagnosis influences the natural history of PCa is
unknown, but it is a reasonable step for physicians to
recommend smoking cessation to PCa patients to improve
their health. Knowledge of tobacco cessation and control
actions should be considered for inclusion in the core
curriculum of urologic oncology training. Although such an
approach will undoubtedly improve overall health, it may
also improve overall PCa outcomes.
Author contributions: Cosimo De Nunzio had full access to all the data in
the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
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