Original article
Clinical—prostate
Smoking and adverse outcomes at radical prostatectomy

https://doi.org/10.1016/j.urolonc.2011.06.013Get rights and content

Abstract

Background

Multiple large epidemiologic studies have examined the relationship between smoking and prostate cancer incidence and mortality only to arrive at contradictory results. In this series, we studied the effect of smoking on pathologic outcomes and biochemical recurrence in a cohort of men undergoing radical prostatectomy.

Methods

We identified 630 men who underwent radical prostatectomy between 1989 and 2005 who had detailed smoking histories. There were 321 smokers and 309 nonsmokers. Pathologic outcomes included prostate weight, volume of cancer, volume of high grade cancer, margin status, seminal vesicle involvement, extraprostatic extension, perineural invasion, angiolymphatic invasion, and the presence of nodal metastasis. Biochemical recurrence was defined as a postoperative PSA ≥ 0.1 ng/ml. Univariate analysis and multivariate linear and Cox regression were used to study the impact of smoking on these outcomes.

Results

The volume of cancer (2.54 vs. 2.16 ml, P = 0.016) and the volume of high grade cancer (0.58 vs. 0.28 ml, P = 0.004) were greater in smokers compared with nonsmokers. Smoking independently predicted greater volumes of cancer and high grade cancer in multivariate analysis. Heavy smokers (≥20 pack-year history) had a greater risk of biochemical recurrence on univariate survival analysis. Smoking also predicted a greater risk of biochemical recurrence on Cox regression, the magnitude of which was approximately 1% per pack-year smoked.

Conclusions

Smoking is associated with adverse pathologic features and a higher risk of biochemical recurrence in men undergoing radical prostatectomy. If confirmed by additional studies, smoking history may need to be included into risk assessment models.

Introduction

Although cigarette smoking has been implicated in many cancers and is the leading cause of cancer mortality, its role in prostate cancer remains ill-defined [1]. Numerous epidemiologic studies have attempted to link smoking with prostate cancer incidence [2], [3], [4], [5] and mortality [6], [7], [8], [9] but have yielded contradictory results. One explanation for these divergent findings may be inherent biases and problems with misclassification of exposure and outcomes associated with large survey-based cohort studies. Additionally, some of these studies utilized cohorts that originated prior to the PSA era and thus their results may not be generalized to contemporary patients. Nevertheless, because prostate cancer accounts for approximately 25% of all newly diagnosed malignancies in US men [10] and the prevalence of cigarette smoking is 21.6% [11], clarifying the influence of smoking on prostate cancer has important public health and clinical implications.

The Stanford Radical Prostatectomy Database (SRPD), a prospectively maintained repository of all radical prostatectomies (RP) performed at our institution, contains information on patient demographics, medical history, pathologic features at the time of surgery, and clinical outcomes. One of its strengths is that it has detailed morphometric data on the total cancer volume and high grade (Gleason pattern 4 and 5) cancer volume as determined by McNeal et al. [12]. Because information on smoking history for these patients was also available, this cohort served as a convenient population in which to study the relationship between cigarette smoking and prostate cancer in patients treated by RP. In this study, we analyzed both pathologic outcomes and biochemical recurrence (BCR).

Section snippets

Study population

With institutional review board approval (Internal Review Board Approval: Approved by the Stanford University School of Medicine IRB, Protocol 11714), we reviewed the SRPD and identified 739 patients who had detailed morphometric information on cancer volume and high grade cancer volume who also had clinical follow-up. Of these, 630 had information on smoking history. The RP were performed from 1989 to 2005 by multiple surgeons. There were 309 nonsmokers and 321 smokers. Smoking history was

Results

The demographics of patients in this series are shown in Table 1. Of the 630 patients included in this study, 309 never smoked while 321 had a history of smoking. Of the smokers, 197 had detailed pack-year information. The median number of pack-years among the smokers was 25 (IQR, 12–40). The distribution of prostatectomies in this cohort over time was reported using intervals previously described, with the vast majority of the cases occurring in the PSA era [15]. The median follow up in this

Discussion

A clear relationship between smoking and prostate cancer has been elusive. While several large scale epidemiologic studies spanning the last 2 decades have hinted at an association between smoking and prostate cancer mortality, conflicting studies have also been published. A large scale retrospective cohort that included over 55,102 men spanning the years 1975 to 2002 showed that those with a ≥20 pack-year history of smoking had a higher risk of death from prostate cancer (RR = 2.38) [6].

Conclusion

For men undergoing radical prostatectomy for prostate cancer, a history of smoking is associated with adverse pathologic features and a higher risk of BCR. If confirmed by additional studies with larger cohorts, smoking history may need to be included into risk assessment models. The biologic basis for this finding remains unclear and warrants further investigation. Whether smoking cessation after surgery influences oncologic outcome or not is unknown.

References (28)

  • T.E. Rohan et al.

    Cigarette smoking and risk of prostate cancer: A population-based case-control study in Ontario and British Columbia, Canada

    Eur J Cancer Prev

    (1997)
  • E. Giovannucci et al.

    Smoking and risk of total and fatal prostate cancer in United States health professionals

    Cancer Epidemiol Biomarkers Prev

    (1999)
  • P.A. Lotufo et al.

    Cigarette smoking and risk of prostate cancer in the physicians' health study (United States)

    Int J Cancer

    (2000)
  • H.O. Adami et al.

    A prospective study of smoking and risk of prostate cancer

    Int J Cancer

    (1996)
  • Cited by (20)

    • Smoking history, intensity, and duration and risk of prostate cancer recurrence among men with prostate cancer who received definitive treatment

      2019, Annals of Epidemiology
      Citation Excerpt :

      Smoking can potentially promote adverse prostate cancer outcomes through multiple mechanisms, including inflammation, exposure to carcinogens, hormonal changes, increased tumor angiogenesis, and genetic mutations [8,11]. However, the evidence regarding the association of smoking status and biochemical recurrence is inconclusive, with some studies suggesting that smoking is positively associated with biochemical recurrence [12–17]; and others reporting no evidence of an association [18–21]. Nonetheless, a 2018 meta-analysis found that both current smoking (pooled hazard ratio [HR]: 1.40, 95% confidence interval [CI]: 1.18, 1.66) and former smoking (pooled HR: 1.19, 95% CI: 1.09, 1.30) were significantly associated with biochemical recurrence [22].

    • Latest Evidence on the Impact of Smoking, Sports, and Sexual Activity as Modifiable Lifestyle Risk Factors for Prostate Cancer Incidence, Recurrence, and Progression: A Systematic Review of the Literature by the European Association of Urology Section of Oncological Urology (ESOU)

      2019, European Urology Focus
      Citation Excerpt :

      In addition, Fowke et al [48] did not find significant differences in CSM in a summary of 18 Asian cohort studies. Overall 16 articles (referring to 14 studies) were identified reporting results of CCSs on mortality and/or treatment outcomes assessed by the end point recurrence or distant failure [50–63]. Fourteen articles reported a consistent association between smoking status and cancer-related death or treatment outcomes [50–61].

    • Smoking and Prostate Cancer: A Systematic Review

      2015, European Urology Focus
      Citation Excerpt :

      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 [45]. 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 [45]. 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).

    View all citing articles on Scopus
    View full text