Back

Platinum Priority – Prostate Cancer
Editorial by Stacey A. Kenfield and Meir J. Stampfer on pp. 957–958 of this issue

Association of Cigarette Smoking and Smoking Cessation with Biochemical Recurrence of Prostate Cancer in Patients Treated with Radical Prostatectomy

By: Malte Rieken a b , Shahrokh F. Shariat a c d , Luis A. Kluth a e , Harun Fajkovic c , Michael Rink e , Pierre I. Karakiewicz f , Christian Seitz c , Alberto Briganti g , Morgan Rouprêt h , Wolfgang Loidl i , Quoc-Dien Trinh j , Alexander Bachmann b and Gholamreza Pourmand k

European Urology, Volume 68 Issue 6, December 2015, Pages 949-956

Published online: 01 December 2015

Keywords: Prostate cancer, Radical prostatectomy, Smoking, Biochemical recurrence

Abstract Full Text Full Text PDF (1,8 MB) Patient Summary

Abstract

Background

Cigarette smoking seems to be associated with prostate cancer (PCa) incidence and mortality.

Objective

To elucidate the association between pretreatment smoking status, cumulative smoking exposure, and time since smoking cessation and the risk of biochemical recurrence (BCR) of PCa in patients treated with radical prostatectomy (RP).

Design, setting, and participants

Retrospective analysis of 6538 patients with pathologically node-negative PCa treated with RP between 2000 and 2011. Clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation were collected.

Intervention

RP without neoadjuvant therapy.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression analyses assessed the association between smoking and risk of PCa BCR.

Results and limitations

Of 6538 patients, 2238 (34%), 2086 (32%), and 2214 (34%) were never, former, and current smokers, respectively. Median follow-up for patients not experiencing BCR was 28 mo (interquartile range 14–42). RP Gleason score (p = 0.3), extracapsular extension (p = 0.2), seminal vesicle invasion (p = 0.8), and positive surgical margins (p = 0.9) were comparable among the three groups. In multivariable Cox regression analysis, former smokers (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.30–2.04; p < 0.001) and current smokers (HR 1.80, 95% CI 1.45–2.24; p < 0.001) had a higher risk of PCa BCR compared with non-smokers. Smoking cessation for ≥10 yr mitigated the risk of BCR in multivariable analyses (HR 0.96, 95% CI 0.68–1.37; p = 0.84). In multivariable analysis, no significant association between cumulative smoking exposure and risk of BCR could be detected. Limitations of the study include the retrospective design and potential recall bias regarding smoking history.

Conclusion

Smoking seems to be associated with a higher risk of PCa BCR after RP. The effects of smoking appear to be mitigated by ≥10 yr of cessation. Smokers should be counseled regarding the detrimental effects of smoking on PCa prognosis.

Patient summary

We investigated the effect of smoking on the risk of prostate cancer recurrence in patients with treated with surgery. We found that former smokers and current smokers were at higher risk of cancer recurrence compared to patients who never smoked; the detrimental effect of smoking was mitigated after 10 yr or more of smoking cessation. We conclude that smokers should be counseled regarding the detrimental effects on prostate cancer outcomes.

Take Home Message

Former and current smoking is associated with a higher risk of biochemical recurrence of prostate cancer after radical prostatectomy when compared to non-smoking. The detrimental effects of smoking seem to be mitigated by ≥10 yr of smoking cessation.

Keywords: Prostate cancer, Radical prostatectomy, Smoking, Biochemical recurrence.

1. Introduction

Tobacco use is a known risk factor for several human cancers [1] . Studies on the association between cigarette smoking and prostate cancer (PCa) have reported contradictory results [2], [3], [4], and [5]. A recent meta-analysis of 33 studies showed that current cigarette smoking was inversely associated with PCa incidence [6] . Results from the studies included in the meta-analysis showed high heterogeneity; many studies conducted in the era before prostate-specific antigen (PSA) screening showed a positive association, in contrast to studies afterwards [6] . One possible explanation for this observation is that smoking may reduce the risk of indolent cancers that have predominated in more recent years, but may promote more aggressive cancers.

While the association between smoking and PCa incidence remains unclear, cigarette smoking seems to be associated with a higher risk of PCa mortality [6] . In addition, the number of cigarettes smoked shows a dose-response association with PCa death [6] . However, studies on the association between smoking and risk of biochemical recurrence (BCR) in PCa patients treated with radical prostatectomy (RP) have yielded conflicting results [7], [8], [9], and [10]. In addition, previous studies did not investigate groups of former smokers [8], [9], and [10], the effect of cumulative exposure [8] and [9], or the effect of time since smoking cessation on the risk of BCR [7], [8], [9], and [10].

The aim of the current study was to investigate the association between smoking status, time since smoking cessation, and cumulative exposure on BCR in patients treated with RP for PCa in a large multi-institutional cohort.

2. Patients and methods

2.1. Patient selection and data collection

This study was approved by the relevant institutional review boards, with all participating sites providing the necessary institutional data-sharing agreements before study initiation. A computerized data bank was generated for data transfer. After combining the data sets, reports were generated for each variable to identify data inconsistencies and other data integrity problems. Through regular communication with all sites, all anomalies identified were resolved before analysis. The database was then frozen and the final data set was produced for analysis. A total of six centers provided data. The study cohort included 7426 patients with clinically localized PCa treated with RP between 2000 and 2011 for whom information on smoking parameters was available. Patients with preoperative PSA >50 ng/ml (n = 15), missing preoperative PSA (n = 45), missing surgical margin status (n = 2), missing information on BCR (n = 18), missing biopsy or RP Gleason score (n = 58), and/or missing follow-up data (n = 97) were excluded from the analysis, leaving 7191 patients. Patients with positive lymph node metastasis (n = 653) were treated with immediate androgen deprivation therapy. As the BCR-free survival endpoint could not properly be analyzed in these patients, all patients with pathologically positive lymph node metastasis were excluded, leaving 6538 patients for final analysis. RP was performed as open (n = 2981, 46%), robot-assisted (n = 3069, 47%), or laparoscopic (n = 488, 7%) surgery. Data were collected from a collective database for various Austrian centers (n = 2780, 43%), Weill Cornell Medical College (New York, NY, USA; n = 2979, 46%), and the University of Texas Southwestern Medical Center (Dallas, TX, USA; n = 779, 12%). No patient received preoperative radiotherapy, hormonal treatment, or chemotherapy. No patient had known distant metastatic disease at the time of RP.

2.2. Pathologic evaluation

All surgical specimens were processed according to standard pathologic procedures as outlined elsewhere [11] . Specimens were totally embedded. The entire specimen was inked on receipt and fixed by immersion in buffered formalin. Whole-mount tissue slices were analyzed according to the protocol in each institution. Genitourinary pathologists assigned pathologic stage; if obtained before 2007, pathologic stage was reassigned according to the 2007 American Joint Committee on Cancer TNM staging system. Lymphoid tissue removed was submitted for histological examination. A positive pathological margin was defined as tumor cells in contact with the inked surface of the RP specimen.

2.3. Follow-up

Follow-up was performed according to institutional protocols. In general, patients were seen postoperatively quarterly within the first year, semiannually in the second year, and annually thereafter. Digital rectal examination and prostate specific antigen (PSA) evaluation were generally performed at each visit. The primary endpoint (BCR) was defined as a PSA value >0.2 ng/ml on two consecutive visits [12] . The date of BCR was defined as the day of the first of these PSA measurements. If a patient died during follow-up, this was not recorded as a BCR event as long as he did not experience BCR before death. No patient received immediate postoperative radiotherapy.

2.4. Statistical analysis

A patient was considered a smoker if he had smoked 100 cigarettes during his lifetime. Patients reporting smoking cessation within 1 yr before RP were considered current smokers. Smoking cessation duration was categorized using 5-yr intervals (1–4.9 yr, 5–9.9 yr, ≥10 yr). Smoking intensity was assessed by calculating the cumulative smoking exposure for patients. According to the number of cigarettes and smoking duration, we divided smokers into four categories of lifetime cumulative smoking exposure: light short-term (≤20 cigarettes per day [CPD] and ≤20 yr), light long-term (≤20 CPD and >20 yr), heavy short-term (>20 CPD and ≤20 yr), and heavy long-term (>20 CPD and >20 yr). Associations between categorical variables were assessed using the χ2 test. The distribution of continuous variables across categories was assessed using the Kruskal-Wallis test. BCR-free survival curves were generated using the Kaplan-Meier method; a log-rank test was applied for pairwise comparisons of survival. The association between smoking and BCR after RP was assessed using univariable Cox regression models. Two sets of multivariable models were fitted. First we estimated the impact of smoking status (never, former, current) on BCR. Then we limited the data set to patients who had ever smoked, and analyzed years since cessation and cumulative smoking exposure with regard to BCR simultaneously. All p values are two-sided and statistical significance was defined as p < 0.05. Statistical analyses were performed using SPSS 20 (IBM Corp, Armonk, NY, USA).

3. Results

3.1. Association between smoking and clinicopathologic features

Table 1 lists clinicopathologic characteristics of the cohort stratified by smoking status. Of 6538 patients, 2238 (34%), 2086 (32%), and 2214 (33%) were never, former, and current smokers, respectively. RP Gleason score (p = 0.3), extracapsular extension (p = 0.2), seminal vesicle invasion (p = 0.8), and positive surgical margins (p = 0.9) were comparable among the three groups. By contrast, men who never smoked had a higher rate of D’Amico high-risk tumors compared to former and current smokers (p < 0.001).

Table 1 Clinicopathologic characteristics of 6538 patients treated with radical prostatectomy for prostate cancer according to smoking status

Characteristic Overall Smoking status p value
Never Former Current
Patients, n (%) 6538 2238 (34.2) 2086 (31.9) 2214 (33.9)
Median age, yr (IQR) 61.0 (9) 61.0 (9) 61.0 (9) 62.0 (9) 0.3
Median preoperative PSA, ng/ml (IQR) 6.0 (5) 6.0 (5) 6.0 (5) 6.0 (5) 0.02
Preoperative Gleason score, n (%)
 ≤6 3798 (58.1) 1112 (49.7) 1324 (63.5) 1362 (61.5) < 0.001
 7 2376 (36.3) 979 (43.7) 666 (31.9) 731 (33.0)
 ≥8 364 (5.6) 147 (6.6) 96 (4.6) 121 (5.5)
Radical prostatectomy Gleason score, n (%)
 ≤6 2179 (33.3) 765 (34.2) 692 (33.2) 722 (32.6) 0.3
 7 4049 (61.9) 1370 (61.2) 1307 (62.7) 1372 (62.0)
 ≥8 310 (4.7) 103 (4.6) 87 (4.2) 120 (5.4)
D’Amico category, n (%)
 Low risk 2987 (45.7) 867 (38.7) 1045 (50.1) 1075 (48.6) <0.001
 Intermediate risk 2889 (44.2) 1098 (49.1) 850 (40.7) 941 (42.5)
 High risk 662 (10.1) 273 (12.2) 191 (9.2) 198 (8.9)
Extracapsular extension, n (%) 1324 (20.3) 453 (20.2) 399 (19.1) 472 (21.3) 0.2
Seminal vesicle invasion, n (%) 289 (4.4) 94 (4.2) 92 (4.4) 103 (4.7) 0.8
Positive surgical margin, n (%) 828 (12.7) 289 (12.9) 263 (12.6) 276 (12.5) 0.9
Cigarettes per day, n (%)
 1–10 493 (11.5) NA 239 (11.5) 254 (11.5) 0.16
 11–20 1194 (27.8) NA 609 (29.2) 585 (26.4)
 21–30 1502 (34.9) NA 723 (34.7) 779 (35.2)
 >30 1111 (25.8) NA 515 (24.7) 596 (26.9)
Years of smoking, n (%)
 ≤10 656 (15.3) NA 317 (15.2) 339 (15.3) < 0.001
 11–20 907 (21.1) NA 453 (21.7) 454 (20.5)
 21–30 1148 (26.7) NA 485 (23.3) 663 (29.9)
 >30 1589 (37.0) NA 831 (39.8) 758 (34.2)
Years since cessation, n (%)
 1–4.9 808 (38.7) NA 808 (38.7) NA NA
 5–9.9 483 (23.2) NA 483 (23.2) NA
 ≥10 795 (38.1) NA 795 (38.1) NA
Cumulative smoking exposure, n (%)
 Light short-term 879 (20.4) NA 443 (21.2) 436 (19.7) 0.16
 Heavy short-term 684 (15.9) NA 327 (15.7) 357 (16.1)
 Light long-term 1050 (24.4) NA 529 (25.4) 521 (23.5)
 Heavy long-term 1687 (39.2) NA 787 (37.7) 900 (40.7)

IQR = interquartile range; PSA = prostate-specific antigen; NA = not applicable.

3.2. Association between smoking status and BCR

The median follow-up for patients not experiencing BCR was 28 mo (interquartile range 14–42). Smoking status was significantly associated with BCR-free survival, with 5-yr BCR-free survival of 90% (standard error [SE] 1%), 84% (SE 1%), and 83% (SE 1%) for never, former, and current smokers, respectively ( Fig. 1 ). In multivariable Cox regression analysis adjusted for the effects of standard clinicopathologic features, former smoking (HR 1.63, 95% confidence interval [CI] 1.30–2.04; p < 0.001) and current smoking (HR 1.80, 95% CI 1.45–2.24; p < 0.001) were associated with higher risk of BCR compared with non-smokers ( Table 2 ). In subgroup analyses, a significant association between smoking and higher risk of BCR was observed for all RP Gleason score categories ( Table 3 ).

gr1

Fig. 1 Kaplan-Meier curves depicting biochemical recurrence–free survival in 6538 patients with adenocarcinoma of the prostate treated with radical prostatectomy according to smoking status. SE = standard error.

Table 2 Multivariable Cox regression analysis predicting biochemical recurrence of prostate cancer in 6538 patients treated with radical prostatectomy according to smoking status

Characteristic Hazard ratio 95% CI p value
Age (continuous) 1.01 0.99–1.02 0.4
PSA (continuous) 1.04 1.03–1.06 <0.001
RP Gleason score
 ≤6 Reference
 7 1.76 1.41–2.19 <0.001
 ≥8 3.20 2.35–4.35 <0.001
Positive surgical margin 1.99 1.67–2.39 <0.001
Extracapsular extension 2.36 1.95–2.86 <0.001
Seminal vesicle invasion 1.87 1.47–2.37 <0.001
Smoking status
 Never Reference
 Former 1.63 1.30–2.04 <0.001
 Current 1.80 1.45–2.24 <0.001

CI = confidence interval; PSA = prostate-specific antigen; RP = radical prostatectomy.

Table 3 Multivariable Cox regression analysis predicting biochemical recurrence in 6538 patients with prostate cancer treated with RP according to smoking status, stratified by RP Gleason score

Characteristic Hazard ratio 95% CI p value
RP Gleason ≤6
 Never smoked Reference
 Former smoker 2.51 1.45–4.35 0.001
 Current smoker 3.06 1.77–5.28 <0.001
RP Gleason 7
 Never smoked Reference
 Former smoker 1.38 1.07–1.79 0.01
 Current smoker 1.35 1.04–1.74 0.02
RP Gleason ≥8
 Never smoked Reference
 Former smoker 3.77 1.55–9.19 0.003
 Current smoker 6.53 2.81–15.19 <0.001

CI = confidence interval; RP = radical prostatectomy.

3.3. Association between cumulative smoking exposure and BCR

We investigated a potential association between smoking intensity and risk of BCR. We divided smokers into four categories according to lifetime cumulative smoking exposure. No significant differences in 5-yr BCR-free survival were observed among the cumulative smoking exposure groups. In multivariable Cox regression analysis, cumulative smoking exposure was not significantly associated with BCR ( Table 4 ).

Table 4 Multivariable Cox regression analysis predicting biochemical recurrence in 4300 patients (former/current smokers) with prostate cancer treated with RP according to cumulative exposure

Characteristic Hazard ratio 95% CI p value
Age (continuous) 1.00 0.99–1.02 0.6
PSA (continuous) 1.04 1.03–1.05 <0.001
RP Gleason score
 ≤6 Reference
 7 1.58 1.25–2.01 <0.001
 ≥8 3.57 2.57–4.97 <0.001
Positive surgical margin 2.14 1.75–2.61 <0.001
Extracapsular extension 2.45 1.98–3.02 <0.001
Seminal vesicle invasion 1.61 1.22–2.12 0.001
Cumulative exposure
 Light short-term Reference
 Heavy short-term 1.14 0.85–1.53 0.4
 Light long-term 0.84 0.64–1.11 0.2
 Heavy long-term 0.92 0.72–1.17 0.5

CI = confidence interval; PSA = prostate-specific antigen; RP = radical prostatectomy.

Multivariable analysis adjusted for age (continuous), preoperative PSA (continuous), surgical margin status, extracapsular extension, seminal vesicle invasion, and smoking status.

3.4. Association between smoking cessation and BCR

We investigated the association between smoking cessation duration and risk of BCR. Smoking cessation duration was significantly associated with BCR ( Fig. 2 ). In multivariable Cox regression analysis, smoking cessation of ≤4.9 yr (HR 1.86, 95% CI 1.43–2.41; p < 0.001) and 5–9.9 yr (HR 2.01, 95% CI 1.50–2.70; p < 0.001) was associated with higher risk of BCR compared with the risk for men who never smoked ( Table 3 ). By contrast, smoking cessation of ≥10 yr was not associated with higher risk of BCR compared to men who never smoked (HR 0.96, 95% CI 0.68–1.37; p = 0.8; Table 5 ).

gr2

Fig. 2 Kaplan-Meier curves depicting biochemical recurrence–free survival in 4324 patients with adenocarcinoma of the prostate treated with radical prostatectomy according to time since smoking cessation. SE = standard error.

Table 5 Multivariable Cox regression analysis predicting biochemical recurrence in 4324 patients (never/former smokers) with prostate cancer treated with RP according to smoking cessation status

Characteristic Hazard ratio 95% CI p value
Age (continuous) 0.99 0.98-1.01 0.6
PSA (continuous) 1.05 1.03-1.06 <0.001
RP Gleason score
 ≤6 Reference
 7 1.84 1.37–2.47 <0.001
 ≥8 1.89 1.19–2.99 0.007
Positive surgical margin 1.76 1.38–2.24 <0.001
Extracapsular extension 2.42 1.88–3.13 <0.001
Seminal vesicle invasion 2.48 1.82–3.39 <0.001
Smoking cessation
 Never smoked Reference
 1–4.9 yr 1.86 1.43–2.41 <0.001
 5–9.9 yr 2.01 1.50–2.70 <0.001
 ≥10 yr 0.96 0.68–1.37 0.8

CI = confidence interval; PSA = prostate-specific antigen; RP = radical prostatectomy.

4. Discussion

We found that smoking status was associated with higher risk of BCR after RP in patients with node-negative disease. Current and former smokers had an almost twofold higher risk of BCR compared with men who never smoked. These results are comparable to previous studies. In an analysis of 630 men treated with RP, heavy smoking defined as ≥20 pack-years as a continuous variable was associated with higher risk of BCR [10] . However, while the multivariable model of this study included volume of cancer and volume of high-grade cancer, there was no adjustment for the effects of tumor stage, Gleason score, or margin and nodal status. Current smoking was also associated with a more than twofold higher risk of BCR compared to men who never smoked in a study of 1416 patients treated with RP [7] . However, this study reported that former smokers were not at higher risk of BCR [7] . By contrast, two other studies relying on data from the Shared Equal Access Regional Cancer Hospital (SEARCH) database showed no association between current smoking and BCR after controlling for the effects of standard pre- and postoperative clinicopathologic parameters [8] and [9].

The mechanisms underlying the detrimental effect of cigarette smoking on PCa biology and prognosis remain largely unclear. In contrast to our results, other studies found that smokers had unfavorable clinicopathologic features at RP suggestive of clinically more aggressive disease in comparison to men who never smoked [8], [9], [10], and [13]. However, given the fact that clinicopathologic features were comparable between smokers and nonsmokers in our study, it remains questionable whether these factors translate into a higher risk of BCR. One potential mechanism linking smoking and PCa recurrence is the induction of heme oxygenase 1 (HO1) expression in PCa cells. In a recent in vitro study, cigarette smoke medium induced HO1 mRNA expression and upregulated HO1 protein levels in the PCa cell lines DU145 and PC3 [14] . Expression of HO1 activated the transcriptional activity of vascular endothelial growth factor (VEGF) and promoted VEGF secretion in PCa cells [14] . As VEGF expression is associated with PCa prognosis [15] , these results warrant further confirmation in animal models.

In the present study, cumulative exposure was not associated with a higher risk of BCR after RP. Ngo et al [10] reported a higher risk of BCR for patients with ≥20 pack-years compared with 0–19 pack-years in a study of 630 patients treated with RP. Similarly, a recent meta-analysis of 12 studies on smoking and PCa mortality found that the number of cigarettes smoked at baseline was associated with PCa mortality [6] . Notably, these studies did not analyze cumulative exposure, and analyses on cumulative cigarette exposure and its association with PCa mortality showed conflicting results [16], [17], [18], and [19]. Further studies should include detailed smoking history to determine the appropriate cut-offs for cumulative smoking exposure and its impact on PCa outcomes.

Smoking appears to be associated with a higher risk of BCR, so we investigated the impact of smoking cessation on PCa prognosis after RP. This is important to see whether urologists could use PCa diagnosis as a teachable moment, as suggested for bladder cancer [20] and [21]. However, it must be acknowledged that our results do not provide any evidence regarding the impact of smoking cessation on PCa outcomes at the time RP. In our study, time since smoking cessation was significantly associated with risk of BCR. Men who stopped smoking <5 yr or 5–9.9 yr before RP were at higher risk of BCR compared to men who never smoked. By contrast, smoking cessation ≥10 yr before surgery put patients at the same risk of BCR as men who never smoked. This suggests that the detrimental effects of smoking may be mitigated after smoking cessation for ≥10 yr, in agreement with observations for cardiovascular disease [22] . Another study found no increase in BCR risk among former smokers compared to men who never smoked [7] . However, the association between time since smoking cessation and risk of BCR has not been previously described in PCa. By contrast, this effect is well characterized in other types of cancer. In patients with urothelial carcinoma of the bladder treated with radical cystectomy, time since smoking cessation was associated with disease recurrence and cancer-specific mortality [23] . Patients with ≥10 yr since cessation had the lowest cumulative incidence of disease recurrence and cancer-specific mortality compared to former smokers who stopped <10 yr previously or current smokers [23] . In various other cancers such as lung, laryngeal, oropharyngeal, and gastric malignancies, long-term cessation reduces the detrimental effects of smoking [24] . Taken together, our results and the evidence available for other cancers suggest that smokers should be counseled on the detrimental effects of smoking on PCa outcomes and the potential benefits of smoking cessation. Our data do not provide any evidence of the impact of smoking cessation on PCa outcomes at the time of surgery. However, we believe that our data contribute to the emerging evidence that doctors should encourage smokers—regardless whether PCa has been diagnosed—to stop smoking. Future interventional trials should further investigate the impact of smoking cessation on PCa outcomes after RP. This could be accomplished by comparing a prospective cohort of PCa patients who stop smoking at diagnosis with a cohort who continue to smoke following RP.

Our study has several limitations, including the retrospective design. As a multicenter study, the cohort of patients underwent RP performed by several surgeons, and several pathologists analyzed the pathologic specimens. However, all physicians were dedicated to uro-oncology. Performance of lymph node dissection and the lymph node dissection templates varied among centers. Comorbidities might have influenced decision-making regarding surgical therapy, introducing a selection bias. Information on comorbidities and performance status was not available, so differences among the groups regarding these parameters could not be assessed. In addition, differences in socioeconomic and dietary background might exist among smokers and nonsmokers. We are aware that the present analysis cannot be adjusted for these potentially relevant parameters. Another bias may have resulted from the exclusion of other tobacco products and different forms of tobacco exposure. We also did not have any information on second-hand smoking exposure or home environment exposure, which might potentially influence the results of our analyses. In addition, smoking history was self-reported and subject to recall bias and honesty. Moreover, patients who did not have smoking data available were excluded from the study, which may have resulted in a selection bias.

5. Conclusions

Current and former cigarette smoking seems to be associated with a higher risk of PCa BCR after RP. According to our retrospective analysis, the effects of cigarette smoking on BCR seem to be mitigated by ≥10 yr of smoking cessation. Smokers should be counseled regarding the detrimental effects of smoking on PCa prognosis. Urologists need to play a broader role in the health care management of our population. The effect of passive smoking and short intervention on overall and PCa-specific mortality needs to be assessed in the future.


Author contributions: Shahrokh F. Shariat 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.

Study concept and design: Rieken, Shariat, Pourmand.

Acquisition of data: Shariat, Fajkovic, Seitz, Briganti, Rouprêt, Loidl, Karakiewicz.

Analysis and interpretation of data: Rieken, Shariat.

Drafting of the manuscript: Rieken, Shariat.

Critical revision of the manuscript for important intellectual content: Kluth, Fajkovic, Rink, Karakiewicz, Seitz, Briganti, Rouprêt, Loidl, Trinh, Bachmann, Pourmand.

Statistical analysis: Rieken, Shariat.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Shariat.

Other (specify): None.

Financial disclosures: Shahrokh F. Shariat certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.

Funding/Support and role of the sponsor: None.

References

  • [1] B. Secretan, K. Straif, R. Baan, et al. A review of human carcinogens—part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 2009;10:1033-1034 Crossref
  • [2] J.M. Bae, Z.M. Li, M.H. Shin, D.H. Kim, M.S. Lee, Y.O. Ahn. Cigarette smoking and prostate cancer risk: negative results of the Seoul Male Cancer Cohort Study. Asian Pac J Cancer Prev. 2013;14:4667-4669 Crossref
  • [3] A.B. Murphy, F. Akereyeni, Y.A. Nyame, et al. Smoking and prostate cancer in a multi-ethnic cohort. Prostate. 2013;73:1518-1528 Crossref
  • [4] S.A. Barry, M.C. Tammemagi, S. Penek, et al. Predictors of adverse smoking outcomes in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. J Natl Cancer Inst. 2012;104:1647-1659 Crossref
  • [5] G. Ray, D.E. Henson, A.M. Schwartz. Cigarette smoking as a cause of cancers other than lung cancer: an exploratory study using the Surveillance, Epidemiology, and End Results program. Chest. 2010;138:491-499 Crossref
  • [6] F. Islami, D.M. Moreira, P. Boffetta, S.J. Freedland. A systematic review and meta-analysis of tobacco use and prostate cancer mortality and incidence in prospective cohort studies. Eur Urol. 2014;66:1054-1064 Crossref
  • [7] C.E. Joshu, A.M. Mondul, C.L. Meinhold, et al. Cigarette smoking and prostate cancer recurrence after prostatectomy. J Natl Cancer Inst. 2011;103:835-838 Crossref
  • [8] D.M. Moreira, J.A. Antonelli, J.C. Presti Jr., et al. Association of cigarette smoking with interval to biochemical recurrence after radical prostatectomy: results from the SEARCH database. Urology. 2010;76:1218-1223 Crossref
  • [9] D.M. Moreira, W.J. Aronson, M.K. Terris, et al. Cigarette smoking is associated with an increased risk of biochemical disease recurrence, metastasis, castration-resistant prostate cancer, and mortality after radical prostatectomy: results from the SEARCH database. Cancer. 2014;120:197-204 Crossref
  • [10] T.C. Ngo, J.J. Lee, J.D. Brooks, R. Nolley, M. Ferrari, J.C. Presti Jr. Smoking and adverse outcomes at radical prostatectomy. Urol Oncol. 2013;31:749-754 Crossref
  • [11] T.M. Wheeler, R.M. Lebovitz. Fresh tissue harvest for research from prostatectomy specimens. Prostate. 1994;25:274-279 Crossref
  • [12] A. Heidenreich, J. Bellmunt, M. Bolla, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011;59:61-71 Crossref
  • [13] W.W. Roberts, E.A. Platz, P.C. Walsh. Association of cigarette smoking with extraprostatic prostate cancer in young men. J Urol. 2003;169:512-516
  • [14] G. Birrane, H. Li, S. Yang, S.D. Tachado, S. Seng. Cigarette smoke induces nuclear translocation of heme oxygenase 1 (HO-1) in prostate cancer cells: nuclear HO-1 promotes vascular endothelial growth factor secretion. Int J Oncol. 2013;42:1919-1928
  • [15] A.F. West, M. O’Donnell, R.G. Charlton, D.E. Neal, H.Y. Leung. Correlation of vascular endothelial growth factor expression with fibroblast growth factor-8 expression and clinico-pathologic parameters in human prostate cancer. Br J Cancer. 2001;85:576-583 Crossref
  • [16] K. Ozasa. Smoking and mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer (JACC). Asian Pac J Cancer Prev. 2007;8(Suppl):89-96
  • [17] J.M. Weir, J.E. Dunn Jr. Smoking and mortality: a prospective study. Cancer. 1970;25:105-112 Crossref
  • [18] E. Giovannucci, E.B. Rimm, A. Ascherio, et al. Smoking and risk of total and fatal prostate cancer in United States health professionals. Cancer Epidemiol Biomarkers Prev. 1999;8:277-282
  • [19] P.A. Lotufo, I.M. Lee, U.A. Ajani, C.H. Hennekens, J.E. Manson. Cigarette smoking and risk of prostate cancer in the physicians’ health study (United States). Int J Cancer. 2000;87:141-144 Crossref
  • [20] J.J. Crivelli, E. Xylinas, L.A. Kluth, M. Rieken, M. Rink, S.F. Shariat. Effect of smoking on outcomes of urothelial carcinoma: a systematic review of the literature. Eur Urol. 2014;65:742-754 Crossref
  • [21] J.C. Bassett, J.L. Gore, A.C. Chi, et al. Impact of a bladder cancer diagnosis on smoking behavior. J Clin Oncol. 2012;30:1871-1878 Crossref
  • [22] K.K. Teo, S. Ounpuu, S. Hawken, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006;368:647-658 Crossref
  • [23] M. Rink, E.C. Zabor, H. Furberg, et al. Impact of smoking and smoking cessation on outcomes in bladder cancer patients treated with radical cystectomy. Eur Urol. 2013;64:456-464 Crossref
  • [24] C.M. Dresler, M.E. Leon, K. Straif, R. Baan, B. Secretan. Reversal of risk upon quitting smoking. Lancet. 2006;368:348-349 Crossref

Footnotes

a Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA

b Department of Urology, University Hospital Basel, Basel, Switzerland

c Department of Urology, Medical University of Vienna, Vienna, Austria

d Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

e Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

f Department of Urology, University of Montreal, Montreal, QC, Canada

g Department of Urology, San Raffaele Scientific Institute, Urological Research Institute, Milan, Italy

h Department of Urology, Hospital Pitié-Salpétrière, Paris, France

i Prostate Cancer Center, Krankenhaus Barmherzige Schwestern Linz, Linz, Austria

j Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA

k Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran

Corresponding author. Department of Urology, Medical University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria. Tel. +43 1 404002615; Fax: +43 1 404002332.

These authors contributed equally.

Place a comment

Your comment *

max length: 5000