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emphasize that most available data on the possible
association of smoking and PCa incidence and mortality
from observational studies are often geographically limited
to a specific area or population with different smoking and
lifestyle behavior and consequently should be considered
exploratory and serve primarily to develop and implement
future clinical trials.
3.3. Association between smoking and prostate cancer outcome
after treatment
Several observational studies have shown that smoking is
associated with worse outcome in patients with PCa
treated with radiotherapy or medical or surgical treatment
). Roberts et al provided evidence that in
352 men undergoing radical retropubic prostatectomy
(RRP) for PCa, a dose-dependent relationship exists between
cigarette smoking, on the one hand, and extraprostatic
disease and Gleason sum 7, on the other. Risk was greatest
for current smokers (OR: 3.85 [95% CI, 1.44–10.33] and
1.76 [95% CI, 0.66–4.72], respectively), although the associa-
tion remained increased for former smokers (OR: 1.49 [95%
CI, 0.92–2.42] and 0.72 [95% CI, 0.44–1.19], respectively)
when compared with nonsmokers (OR: 1.66 [95% CI, 1.04–
2.65] and 0.81 [95% CI, 0.5–1.30], respectively). A recent
study confirmed this observation and showed a significant
difference in PCa volume (2.54 vs 2.16 ml; p = 0.016) as well
as high-grade cancer volume (0.58 vs 0.28 ml; p = 0.004)
when comparing smokers and nonsmokers . Smoking
also heralded a greater risk of biochemical recurrence
(hazard ratio [HR]: 1.27; 95% CI, 1.03–1.54; p = 0.02), the
magnitude of which was approximately 1% per pack-year
smoked .
Recent data from the Shared Equal Access Regional Cancer
Hospital Cohort (SEARCH) database confirmed that active
smoking was associated, after adjusting for preoperative
features, with an increased risk of biochemical recurrence
(HR: 1.25; p = 0.024), metastasis (HR: 2.64; p = 0.026), and
overall mortality (HR: 2.14; p < 0.001). Similar results were
noted after further adjustment for postoperative features,
with the exception of BCR (HR: 1.10; p = 0.335), metastasis
(HR: 2.51; p = 0.044), and death (HR: 2.03; p < 0.001) .
Data from the Health Professionals Follow-up Study also
confirmed a direct relationship between the number of
cigarettes smoked and inferior treatment outcome in PCa
patients . Current smokers of 40 pack-years, versus
never-smokers, had an increased risk of PCa mortality (HR:
1.82; 95% CI, 1.03–3.20) and BCR (HR: 1.48: 95% CI, 0.88–
2.48). Compared with current smokers, those who had quit
smoking for 10 yr(HR: 0.60; 95% CI, 0.42–0.87) or who had
quit for <10 yr but smoked <20 pack-years (HR: 0.64; 95%
CI, 0.28–1.45) had PCa mortality risk similar to never
smokers (HR: 0.61; 95% CI, 0.42–0.88).
A single experience from Asia does not support the
association between smoking and a worse treatment
outcome in patients treated with RRP, although the
association was evident in obese patients . However,
this single negative outcome related to a retrospective
study in a Korean population could also reflect different
cultural and lifestyle backgrounds when compared with
data from the United States. For men undergoing RRP for
PCa, a history of smoking is associated with adverse
pathologic features and a higher risk of biochemical failure.
If confirmed in large cohort studies, smoking history could
be considered an important risk factor in evaluating
patients with PCa treated with RRP.
A similar scenario is evident for radiotherapy. Pantarotto
et al investigated 434 patients affected by PCa and
treated by external beam radiotherapy (EBRT). A signifi-
cantly (p = 0.007) higher proportion of current smokers
(24.3%) had distant failure events when compared with
nonsmokers (7.6%) or previous smokers (16.9%). Smoking
was associated with a higher risk of developing metastatic
disease in both current smokers (HR: 5.24; 95% CI, 1.75–
15.72) and previous smokers (HR: 2.90; 95% CI, 1.09–7.67).
However, it was unclear when or if the risk of distant failure
was reduced after stopping smoking. Overall survival was
also significantly worse for current smokers than non-
smokers (45.7% vs 25.8%; log-rank test: 0.03), but no
significant differences were observed in PCa-specific
mortality. Similar results were obtained by Pickles et al
who followed 601 men receiving EBRT and documen-
ted 28 PCa deaths; they reported a worse 5-yr biochemical
outcome for smokers than for former smokers or non-
smokers (55%, 69%, and 73%, respectively; p = 0.01 and
p = 0.0019), but no significant increase in PCa-specific
deaths between smokers (10%) and nonsmokers or former
smokers (3.7%; p = 0.08) was observed . Merrick et al
evaluated the same association in patients treated by
brachytherapy. Although no statistically significant differ-
ence was found in biochemical progression-free survival
at 7 yr, a trend for poorer biochemical outcome was
demonstrated in current smokers when compared with
former smokers or nonsmokers (91.6%, 95.6%, and 96.2%,
respectively; p = 0.126) .
A lower quality of life assessed through different
standardized questionnaires such as the Short Form-12
(SF-12) and the Expanded Prostate Index Composite (EPIC-
26) was observed in the follow-up (minimum 1 yr) of
patients who smoked and who were treated by EBRT.
Mean urinary incontinence score was lower ( 9.6 points;
p = 0.019) in smokers compared with nonsmokers. Further-
more, smoking reduced the mean bowel score ( 9.2;
p = 0.023) and the mean sexual score ( 9.9; p = 0.0023).
Current smokers had an increased risk of moderate to
severe problems with the SF-12 vitality measure (OR: 2.9;
p = 0.034), with the EPIC bowel overall bother measure (OR:
7.8; p = 0.003), and with the EPIC sexual overall bother
measure (OR: 2.6; p = 0.0035) .
All of these studies, although limited to small retro-
spective serieswith short follow-up, supported the concept
that current smokers treated with EBRT have worse tumor
control than former smokers. One possible explanation
is related to more aggressive cancer observed in current
smokers and to reduced tissue oxygenation that is
required for radiotherapy efficacy to kill tumor cells.
Current smoking increases carboxyhemoglobin, which has
been shown in experimental models to decrease tumor
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