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. Author manuscript; available in PMC: 2023 Oct 1.
Published in final edited form as: Cancer Epidemiol. 2022 Aug 18;80:102237. doi: 10.1016/j.canep.2022.102237

Systematic Review of Smoking Relapse Rates Among Cancer Survivors Who Quit Time of Cancer Diagnosis

Zachary Feuer 1, Jamie Michael 2, Elizabeth Morton 3, Richard S Matulewicz 4, Paschal Sheeran 5,6, Kimberly Shoenbill 6,7,8, Adam Goldstein 6,7, Scott Sherman 9, Marc A Bjurlin 6,10,*
PMCID: PMC10363369  NIHMSID: NIHMS1915272  PMID: 35988307

Abstract

Background:

Tobacco cessation, at the time of cancer diagnosis, has been associated with better oncologic outcomes. Cancer diagnosis has been shown to serves as a “teachable moment,” inspiring tobacco cessation. However, the sustainability of abstinence from smoking is understudied. Similarly, there is a paucity of data regarding the utility of behavioral/pharmacologic intervention to support continued smoking cessation.

Methods:

A systematic literature review was conducted in August 2021 with no date limits. Relevant studies that reported tobacco smoking relapse rates for patients who quit at the time of cancer diagnosis were included. Our literature search identified 1,620 articles and 29 met inclusion criteria. The primary endpoint of the study was smoking relapse rate. Secondary outcome was a descriptive assessment of behavioral and pharmacologic interventions to promote continued cessation. Exploratory outcomes included a regression analysis to examine associations between study factors and relapse rates.

Results:

There were 3,021 smokers who quit at the time of cancer diagnosis. Weighted overall relapse rate for the study population was 44% (range 5–57%). Interventions to support smoking cessation were employed in 17 of the 29 included studies and protocols were heterogenous, including behavioral, pharmacologic, or mixed intervention strategies. Exploratory analysis demonstrated no association between relapse rates and publication year, gender, or study type. Relapse rates were indirectly associated with age (p=0.003), suggesting that younger patients were more likely to relapse.

Conclusion:

The sustainability of smoking cessation after a cancer diagnosis is understudied, and existing literature is difficult to interpret due to heterogeneity. Relapse rates remain significant and, although many studies have included the employment of an intervention to promote continued cessation, few studies have measured the effect of a protocolized intervention to support abstinence.

Introduction

Tobacco use is associated with increased risk of many cancers. Smoking cessation after cancer diagnosis has the potential to lower risk of recurrence, progression, surgical complications, and disease-specific mortality [1–4]. The diagnosis of cancer serves as a ‘teachable moment’ at which time patients are more likely to quit [5, 6]. For patients with a newly diagnosed smoking-related cancer, tobacco cessation rates range from 48% to 86% [6–10]. This is substantially higher than rates reported in the general population, which range from 2% to 10% [6, 11]. Furthermore, studies have shown that tobacco cessation can be more successful with interventions such as counseling and nicotine replacement treatment, and for those with substantial social support [12].

Although cancer diagnosis can provide additional motivation for smoking cessation, tobacco dependence is a chronic illness that often requires repeated cessation attempts and sustained smoking cessation is challenging. As a result, patients frequently relapse [12]. Previous studies have demonstrated that despite initial cessation after initial cancer diagnosis, many patients relapse, implying that this initial event is not a sustainable motivator [13–16]. However, these studies are often small, single-institution studies with heterogenous methodology, and therefore, difficult to interpret in the context of the general population. Factors such as negative mood, cravings, and withdrawal symptoms have been reported as contributors to relapse in the general population [17]. Patients harboring a new cancer diagnosis may be more prone to smoking relapse secondary to cancer-associated stressors such as depression and anxiety attributed to cancer recurrence [15].

Prior studies have assessed the utility of interventions to promote smoking cessation amongst cancer survivors [18]. However, a paucity of data exists that quantifies the sustainability of smoking cessation in the initial period after a cancer diagnosis. The primary objective of this review is to investigate current literature to determine the rates of smoking relapse among patients who have quit smoking following a cancer diagnosis. Secondarily, we sought to investigate the use of various interventions to aid patients in the goal of smoking cessation.

Methods

A systematic review of literature was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search was intended to identify literature assessing the rate of tobacco smoking relapse amongst patients who attempted cessation after a cancer diagnosis. Our search was conducted on August 2nd, 2021. The protocol for this systematic review was registered to PROSPERO on March 20th, 2022.

Search Strategy

Literature searches were performed by a medical librarian in the PubMed (pubmed.ncbi.nlm.nih.gov), Embase (Embase.com), PsycInfo (EBSCO), Cochrane Database of Systematic Reviews (cochranelibrary.com), and Cochrane CENTRAL (cochranelibrary.com) for English language articles. Key words including various terms for “cancer” (neoplasia, tumor, etc), “tobacco/smoking cessation” (quit, stop, etc) and “relapse” (recurrence, sustainability of cessation) to perform literature review. The complete search terms are provided in Supplemental Table 1.

Eligibility criteria

All studies that included 1) tobacco smoking cessation at the time of cancer diagnosis and 2) time to tobacco smoking relapse were included in this study. The rate of tobacco smoking relapse had to either be calculable or provided for inclusion. Studies in which smoking cessation occurred prior to cancer diagnosis were excluded. Further, included publications were required to be primary studies, written in English. Review articles, abstracts and case reports were excluded. Studies related to e-cigarette use were excluded. Studies were not excluded on the basis of publication date.

Data Extraction

Data extraction was performed in three steps using the Covidence systematic review software package (Covidence.org). First, titles and abstracts were assessed for inclusion by two authors (JM, ZF). Second, full text evaluation of each study deemed eligible after initial screening was performed by two authors (JM, ZF). Studies agreed upon by both authors were included in the final analysis, while those studies which received only one vote for inclusion were highlighted. In these cases, consensus was determined by a third author (MB). Finally, data extraction was performed by two authors (JM, ZF) and reviewed by all co-authors for accuracy. Disagreements were arbitrated by discussion.

Quality Appraisal

Quality of included observational studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) tool. This tool provides an outline for determining the risk of bias in each subsection of an observational study (i.e. abstract, introduction, methods, etc) using checklist items. In total, the STROBE tool includes 22 criteria, thus studies were scored from 0 to 22 on the basis of meeting each criteria. Studies receiving ≥20 points were considered “low risk”, 18–21 points “moderate risk”, 10–18 points “high risk” and <10 points “very high risk.”

For randomized control trials, the Cochrane Collaboration Risk-of-Bias tool, version 2, was employed. This tool assesses randomization, deviation from intervention, missing data, outcome measurement and selection of reported results as subcategories for determining risk of bias. Studies considered low-risk in all five domains were considered “good”, those not meeting 1 domain were considered “fair,” those not meeting 1 domain criteria with concern for effect on the outcome were considered “poor,” and those not meeting 2 or more of the domain criteria were considered “very poor.” All bias assessments were conducted by two authors (JM, ZF) and co-verified.

Evidence Synthesis

Study demographic data and results were summarized. Primary cancer site, percentage of patients quitting tobacco at time of diagnosis, relapse rate and time to relapse were collected. These data were collected in tabular format. Descriptive statistics were generated for patient demographics, including number of patients in the study cohort, patient age, and percentage female. Cigarette use was reported as per day with average and percentage relapsed. Quit rate assessment time point for each study was presented either by the study-defined timepoint, or average follow-up time. Smoking cessation aids were assessed qualitatively and categorized into behavioral, pharmacotherapy-based intervention, or both.

Study Selection

A total of 1,317 studies were screened in Covidence after removal of duplicates (Figure 1). There were 1,156 items excluded in the initial titles/abstracts review, with 157 articles subsequently undergoing full text review. In all, 29 studies were included in the final analysis after excluding 128 publications (Figure 1).

Figure 1:

Figure 1:

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Study PRISMA Diagram

Study Sources

Amongst the 29 studies included in the final analysis, there were 8,240 total patients included. Of the included studies, 24 (83%) were observational [7,8,13,15,16,19–25,27,29–30,33,34–36,38–42] and 5 (17%) were interventional randomized controlled trials (RCTs) [26,28,31,32,37]. Amongst the observational studies, study designs included 6 longitudinal [15,16,19,25,33,34], 8 prospective [7,20–24,27,36], and 3 cross -sectional [8,29,30]. There were 19 (66%) studies completed in North America, 5 (17%) in Europe, 3 (10%) in Australia, 1 in the Middle East (3%), and 1 in Asia (3%). Two (7%) studies utilized population-based datasets, while 20 (69%) studies were conducted at a single institution and 7 (24%) were multi-institutional. There were 17 (59%) studies representing patients with a single primary cancer site, which included 8 (28%) lung cancer, 8 (28%) head and neck cancer, and 1 (3%) genitourinary cancer cohorts. The remaining 12 (41%) of studies included patients with various primary cancer sites. Eighteen (62%) studies featured an intervention comprised of mixed protocols including behavioral therapy, pharmacotherapy (nicotine replacement), or both. Many studies featured non-standardized intervention protocols, based upon provider and/or patient preference, in which patients received different combinations of no intervention, behavioral therapy and pharmacotherapy.

Statistical Analysis

Statistical analyses were performed using SPSS v28 (IBM, Chicago, IL). Weighted least squares regression was employed to determine the strength of association between study factors and smoking relapse rates.

Results

Study Characteristics

Of the 8,240 patients included, participants average age ranged from 54–69 years (mean 60 years) and percent female ranged from 8.6%−100% (mean 44%). A majority of studies were performed using questionnaires and were conducted out of a single institution (Table 1).

Table 1:

Characteristics of Included Studies

Authors / Year Study Years Study Type and Instrument Average age % Female Data Source Countries
Chen 2014 2007–2013 Longitudinal study 58 42 Institutional databases USA
Cooley 2007 2002–2006 Prospective survey 65 100 Patients, 5 centers USA
Cooley 2009 2002–2006 Prospective survey 63 57.5 Patients, 4 centers USA
deBruin-Visser 2012 2003–2005 Prospective 55.7 46 Patients, 1 center Netherlands
Farley 2016 2010–2011 Prospective survey 69 45 Patients, 1 center UK
Guimond 2017 NR Prospective cohort 54 48 Patients, 1 center Canada
Humphris 2004 1996–1998 Longitudinal design 58.3 30 Patients, 1 center Scotland & UK
Krebs 2019 NR RCT 57.1 71 Patients, 1 center USA
Maher 2003 NR Prospective survey 59 39 Patients, 1 center USA
Martinez 2018 2012–2018 RCT 54.9 51 Patients, 1 center USA
Matulewicz 2021 2014–2018 Cross-sectional NR NR National Health Interview Survey USA
Naresh 2020 NR Cross-sectional NR 8.6 Patients, 1 center India
Ostroff 2013 NR RCT 55.9 53 Patients, 1 center USA
Ostroff 1995 1991–1992 Cross-sectional 61.5 33 Patients, 1 center USA
Park 2020 2013–2017 RCT 58.3 56 Patients, 2 centers USA
Paul 2019 2006 Longitudinal study NR NR Patients, 1 center Australia
SandersonCox 2002 1994–1999 Prospective study 62.7 37 North Central Cancer Treatment Group Trial, Patients USA
Schnoll 2003 NR Longitudinal study 57 49 Patients, 1 center USA
Schnoll 2002 NR Cross-sectional 57 49 Patients, 1 center USA
Sheikh 2021 2007–2020 Prospective cohort 61.3 11.4 Patients, 2 centers Russia
Simmons 2013 2008–2009 Longitudinal study 58.3 43 Patients, 1 center USA
Simmons 2020 2012–2020 2-arm, parallel design 55 51.8 Patients, 1 center USA
Smailey 2021 2016–2019 RCT 60 34 Patients, 3 centers Lebanon
Smith 2020 2018–2020 Explanatory sequential mixed methods design 60 15 5-year prospective single institution cohort study Australia
Smith 2021 2018–2020 Explanatory sequential mixed methods design 60 15 5-year prospective single institution cohort study Australia
Tomek 2003 1985–2000 Retrospective study NR NR Institutional Database, 1 center USA
Vitzthum 2015 2011–2013 Retrospective study 68.7 36.6 Patients, 1 center Germany
Walker 2004 2000 Retrospective study 65 42 Cancer Registry, Patients, 1 center USA
Walker 2006 2001–2005 Longitudinal study 58.5 52 Patients, 2 centers USA
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NR=not reported, USA=United States of America, UK=United Kingdom, RCT=randomized controlled trial

Smoking characteristics and Relapse rates

A majority of studies analyzed focused on tobacco-related tumors including head and neck, lung, breast, and bladder cancer. Baseline cigarette use per day prior to smoking cessation ranged from an 10 – 31.5 cigarettes per day, with an overall mean of 21.4 cigarettes per day. Quit rate assessment time points were conducted between 2 months and 7 years after cancer diagnosis. After examining the 29 included studies, we found that relapse rates at various time points ranged from 5.1% to 57% (average 32%), representing a wide range of findings. One study conducted by Walker et al found that in a study period of 12 months, 57% (53/93) of participants who quit at diagnosis had relapsed to smoking. In contrast, Sheikh et al examined 157 participants for an average of 7 years and found that only 8 participants relapsed (5.1%). (Table 2). These studies did not employ significant interventions to encourage sustained smoking cessation, and the former study, demonstrating a higher relapse rate, incorporated a shorter observation period. The major differences between these studies included the location and time period in which each were conducted, as the former study was published using data collected in the United States in 2004, while the latter was published using data collected in a Russian cohort in 2021.

Table 2:

Smoking, Cancer Characteristics, and Relapse Rates

Author / Year Cancer Type n Baseline cigarettes/day % relapse Quit rate assessment time point
Chen 2014 Head & Neck 49 20 53% (23/49) end of RT
Cooley 2007 NSCLC 70 22.7 30% (21/70) Average 2.5 years
Cooley 2009 NSCLC 21 17 52% (11/21) 4 months
deBruin-Visser 2012 Lung, Head & Neck, Breast, Sarcoma, GU, others 58 20 17% (10/58) 12 months
Farley 2016 Lung cancer 6 NR 50% (3/6) 3 months
Gulmond 2014 Breast, GU, GI, Gyn, Head & Neck 55 16 49.1% (27/55) 4 months
Humphris 2004 Oral 53 17 13% (7/53) 15 months
Krebs 2019 Lung, GI, others 20 NR 70% (14/20) 1 month
Maher 2003 Lung, Head & Neck 93 31.5 12% (12/93) 3 months
Martinez 2018 Lung, Head & Neck, AML, GU, Gyn, GI, Liver, Pancreas, others 357 20.8 25% (91/357) 2 months
Matulewicz 2021 GU 2664 NR Unable to assess
Naresh 2020 Head & Neck 500 NR 15% (75/500) 2 years
Ostroff 2013 Thoracic, Head & Neck, Breast, GYN, GU, others 83 19.5 30% (25/83) 6 months
Ostroff 1995 Head & Neck 74 27.76 35% (26/74) Mean: 217 days
Park 2020 Breast, GI, GU, Gyn, Head & Neck, Lung, Lymphoma, Melanoma 74 10 29.7% (22/74) 6 months
Paul 2019 GU, GI, Breast, Lung, Melanoma, Heme, Head & Neck 91 NR 22% (20/91) 3.5 years
SandersonCox 2002 NSCLC 20 20 10% (2/20) Mean: 14.9 months
Schnoll 2003 Head & Neck, Lung 30 NR 23% (7/30) 3 months
Schnoll 2002 Head & Neck, Lung 30 NR 23% (7/30) 3 months
Sheikh 2021 NSCLC 157 NR 5.1% (8/157) average 7 year
Simmons 2013 Head & Neck, Thoracic 52 24.1 13% (7/52) 12 months
Simmons 2020 Thoracic, Head & Neck, GI, Breast, GU, Gyn, Heme, Cutaneous, others 182 21.6 33% (60/182) 12 months
Smailey 2021 Head & Neck SCC 56 42 30% (17/56) 12 months
Smith 2020 Head & Neck SCC 18 50 pack years 48% (8/18) 3 months
Smith 2021 Head & Neck 21 42 pack years 57% (12/21) 3 months
Tomek 2003 Second Head & Neck tumor 91 NR Unable to assess 6 months
Vitzthum 2015 Lung 131 NR 22% (29/131) End of therapy
Walker 2004 NSCLC 43 NR 44% (19/43) Mean: 33 months
Walker 2006 NSCLC 93 24.6 57% (53/93) 12 months
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RT=Radiation Therapy, NSCLC=non-small cell Lung Cancer, GU=Genitourinary, GI=Gastrointestinal, Gyn=Gynecological, AML=Acute Myeloid Leukemia, SCC=Squamous Cell Carcinoma

Many studies (14/29, 49%) assessed factors associated with smoking relapse in patients who quit smoking after receiving a cancer diagnosis. Depression was demonstrated to be associated with higher relapse rates in 43% (6/14) of studies addressing predictors of relapse. Similarly younger age, high addication levels and male gender were each associated with higher relapse rates in 21% of studies. Finally, lower education levels and lower readiness to quit were associated with higher relapse rates in 35% of studies.

Smoking Cessation Interventions

Of the 29 included studies, 17 reported which type of smoking cessation interventions were used by participants [8,13,15,19–22,26,28,29,31,32,37,39,41,42]. A majority of these described various behavioral interventions, including cognitive behavioral therapy, acupuncture, hypnosis, social support, and physician recommendation. The pharmacological interventions used included bupropion, varenicline, and various forms of nicotine replacement therapy (NRT). One study conducted by Vitzhum et al specifically reported 9.8% of ex-smokers using NRT, 2.2% of ex-smokers using varenicline and 0% of ex-smokers using bupropion [41]. (Table 3)

Table 3:

Summary of Smoking Cessation Interventions

Author/Year Interventions
Chen/2014 Brief counseling, Telephone interview, Buproprion 150mg orally
Cooley 2007 19% received counseling, 31% received education, and 89% used nicotine replacement treatment
Cooley 2009 46% of those who were smoking at diagnosis received cessation assistance with pharmacotherapy being the most common strategy: Bupropion only 24%, NRT only 24%, Bupropion + NRT 6%, Bupropion + information 6%, Information + NRT 18%, Counseling + pharmacotherapy 6%
deBruin-Visser 2012 Counseling, patch (26%), lozenges (12%), Buproprion (2%), combination lozenges and patch (21%), combination patches and buproprion (1%)
Farley 2016 NR
Gulmond 2014 NR
Humphris 2004 NR
Krebs 2019 Behavioral, NRT in 37.5%
Maher 2003 NR
Martinez 2018 Behavioral
Matulewicz 2021 Behavioral (advised to quit smoking by health professional)
Naresh 2020 NR
Ostroff 2013 Behavioral + NRT
Ostroff 1995 Physician recommendations (39%), Support from family and friends (35%), NRT (31%)
Park 2020 Behavioral + pharmacologic (NRT, Buproprion, Varenicline)
Paul 2019 NR
SandersonCox 2002 NR
Schnoll 2003 NR
Schnoll 2002 NR
Sheikh 2021 NR
Simmons 2013 NR
Simmons 2020 Behavioral
Smailey 2021 Behavioral and NRT
Smith 2020 Behavioral and option of NRT
Smith 2021 Behavioral and option of NRT
Tomek 2003 NR
Vitzthum 2015 behavioral (CBT, acupuncture, hypnosis, books, etc) and pharmacologic: NRT (9.8% ex-smokers, 24.1% smokers), varenicline (2.2% ex-smokers, 0% smokers), bupropion (0% ex-smokers, 3.4% smokers)
Walker 2004 NRT (26%)
Walker 2006 NRT (13.1%)
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NR=Not Recorded, NRT=Nicotine Replacement Therapy, CBT=cognitive behavioral therapy

Amongst the studies that reported use of smoking cessation interventions, most of the included studies reported the number of patients that were exposed to each intervention without assessing the utility. Only two studies directly measured the effect of an intervention [13,32]. Park et al compared a cohort of 135 patients who received four weekly counseling phone calls and medication advice to a group of 148 patients who received an intensive therapy regimen, which included an additional four biweekly counseling phone calls, three monthly phone calls, and a cessation medication of their choice. The authors demonstrated an improved quit rate 34.5% versus 21.5% in favor of the cohort receiving intensive intervention [32]. However, this study aimed to assess quit rate, rather than relapse rate.

Simmons et al addressed the utility of a smoking relapse prevention program for patients with a cancer diagnosis who recently quit smoking. They compared patients who received a brief counseling session and pharmacotherapy medication as needed, to a group of patients who received additional relapse prevention material (DVD set and monthly booklets). The monthly booklets addressed topics associated with smoking cessation (i.e. “Smoking Urges” and “Life Without Cigarettes”) while the DVDs included patient testimonials and motivational messages. The authors demonstrated an overall relapse rate of 33%, with no difference between intervention and control groups [13].

Exploratory Analysis

We undertook exploratory analyses using Weighted Least Square (WLS) regression to examine moderators of relapse rates. There was sufficient data to test whether year of publication, demographic characteristics (age, gender), and study design (prospective/RCT = 1, cross-sectional/retrospective = 0) were associated with relapse rates. The sample size in each study was the weighting factor.

Findings showed no association between year of publication and relapse rates (B = 1.03, SE = .83, p = .23), suggesting that relapse rates did not change between 2003 and 2020. Gender was not associated with relapse rates (B = −.32, SE = .29, p = .27) but age showed a negative association (B = −3.47, SE = 1.03, p = .003). Greater mean age of the sample was related to lower relapse rates. Study design was not related to relapse rates (B = −18.73, SE = 11.59, p = .12).

Risk of Bias Analysis

Risk of methodological bias, as assessed by the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist for non-interventional studies and the Cochrane Risk of Bias Tool for randomized controlled trials, was variable among studies. Many of the non-interventional studies lacked descriptive study design terms in their title or abstract, inhibiting the reader from easily identifying the design that was used. Of included randomized controlled trials, many failed to detail their randomization and allocation concealment processes in the methods, leading to an overall assessment of fair, poor, or very poor (Table 4, Table 5). Notably, none of the studies received funding from the tobacco industry.

Table 4:

STROBE Checklist Risk of Bias Analysis

Authors Year Title and Abstract (n/1) Introduction (n/2) Methods (n/9) Results (n/5) Discussion (n/4) Other (n/1) Overall
Chen 2014 0/1 2/2 8/9 5/5 3/4 1/1 Fair
Cooley 2007 0/1 2/2 7/9 5/5 4/4 1/1 Fair
Cooley 2009 1/1 2/2 9/9 5/5 3/4 0/1 Good
deBruin-Visser 2012  0/1  2/2  5/9  5/5  3/4  0/1  Poor
Farley 2016 1/1 2/2 7/9 5/5 3/4 1/1 Fair
Guimond 2017 1/1 2/2 8/9 5/5 4/4 1/1 Good
Humphris 2004 0/1 2/2 8/9 5/5 3/4 1/1 Fair
Maher 2003 0/1 2/2 7/9 5/5 4/4 1/1 Fair
Martinez 2018 1/1 2/2 7/9 5/5 4/4 1/1 Good
Matulewicz 2021 1/1 2/2 8/9 3/5 4/4 1/1 Fair
Naresh 2020 1/1 2/2 7/9 4/5 3/4 1/1 Fair
Ostroff 1995 0/1 2/2 8/9 5/5 4/4 1/1 Good
Paul 2019 1/1 1/2 7/9 4/5 4/4 1/1 Fair
SandersonCox 2002 0/1 1/2 8/9 5/5 4/4 1/1 Fair
Schnoll 2003 1/1 2/2 8/9 5/5 4/4 1/1 Good
Schnoll 2002 0/1 2/2 7/9 4/5 4/4 1/1 Fair
Sheikh 2021 0/1 2/2 8/9 5/5 4/4 1/1 Good
Simmons 2013 1/1 1/2 8/9 5/5 4/4 1/1 Good
Smith 2020 1/1 1/2 6/9 5/5 4/4 1/1 Fair
Smith 2021 1/1 1/2 6/9 5/5 4/4 1/1 Fair
Tomek 2003 0/1 1/2 3/9 2/5 2/4 1/1 Very Poor
Vitzthum 2015 1/1 2/2 8/9 5/5 4/4 1/1 Good
Walker 2004 1/1 2/2 9/9 5/5 4/4 1/1 Good
Walker 2006 0/1 2/2 8/9 5/5 4/4 1/1 Good
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Table 5:

Cochrane Risk of Bias Analysis

Author Year D1 D2 D3 D4 D5 D6 D7 Overall
Park 2020 Low Low Low Low Low Low Low Good
Simmons 2020 Low Low Low Low Low Low Low Good
Smailey 2021 Unclear Unclear Low Low High Low Low Very poor
Krebs 2019 Unclear Unclear Low Low High Low Low Poor
Ostroff 2013 Low Low Low Low High Unclear Low Fair
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D1: Random sequence generation, D2: Allocation concealment, D3: Selective reporting,

D4: Other bias, D5: Blinding of participants, D6: Blinding of outcome assessment,

D7: Incomplete outcome data

Discussion

The primary objective of this study was to evaluate smoking relapse rates, after an initial period of cessation, following a cancer diagnosis. We found that relapse rates varied widely, from 5% to nearly 60% of patients returning to cigarette smoking during respective study periods. The wide range of relapse rates are not surprising given the heterogeneity amongst the included studies. First, very few studies included a primary endpoint aimed at determining sustainability of smoking cessation after cancer diagnosis. Instead, relapse rates were often a secondary or exploratory outcome. Second, methods for determining relapse were nonstandardized, as different studies included either subjective and/or objective measures of smoking cessation. Third, timepoints for the assessment of sustained cessation differed substantially. One of the included studies assessing continued abstinence rates amongst patients randomized to either a usual care or evidenced based smoking relapse prevention group demonstrated a 37% and 32% 12-month relapse rate, respectively [13]. Given the standardized methodology and inclusion of patients with multiple different primary cancer types, the control group in this study may represent a more accurate and generalizable relapse rate without intervention.

As a secondary outcome, we aimed to determine whether interventions, either behavioral or pharmacologic, were employed to aid with continued smoking cessation. Of the 29 included studies, 17 incorporated an intervention. Amongst those studies that included interventions, behavioral and/or pharmacologic interventions were employed, although utilization was inconsistent in many studies. Nevertheless, a significant proportion of patients relapsed after an initial period of cessation, highlighting the need to continue to readdress cessation throughout the period following cancer diagnosis. These findings suggest that, despite evidence that cancer diagnosis provides a “teachable moment” to promote smoking cessation,[43] continued counseling and/or pharmacologic intervention may be necessary for maintenance.[44] This is especially important in this population, given that stress associated with cancer diagnosis and treatment has been demonstrated to be an independent risk factor for relapse.[45] These assertions are supported by the findings in this study.

It is important to note that a significant proportion of included studies did not employ an intervention, especially given that National Cancer Care Network (NCCN) guidelines recommend behavioral counseling and suggest considering nicotine replacement therapy/pharmacotherapies. [46] Although no specific intervention is considered superior, interventions are associated with lower relapse rates amongst patients with cancer.[47] However, importantly, interventions that are efficacious in the general population appear to be less effective for patients with cancer.[48] This may be secondary to the fact that patients who develop smoking-related cancers may be more heavily dependent on tobacco. Nevertheless, the omission of exploratory interventions in many of the included studies represents an opportunity for improvement in clinical practice.

Many of the included studies were performed in cancer site-specific cohorts, and relapse rates were infrequently reported by primary site. A prior study assessing patients’ causative association between smoking and bladder cancer demonstrated that smokers were more aware of this association than expected.[49] However, considering the substantial public health efforts to spread awareness regarding the relationship between certain cancer sites (i.e. lung, head and neck, etc.) and smoking,[50] cancer site may impact relapse rates. Future studies should aim to assess differences in relapse rates by primary cancer site to determine if a specific cohort requires more intensive intervention. To improve abstinence rates, tobacco cessation interventions must be employed regardless of primary cancer site. It has recently been suggested that guidelines for smoking related malignancies be more consistent in recommending tobacco cessation interventions throughout the cancer care continuum.[51] Others have suggested that interventions should target individuals that are at high-risk for relapse, if we can optimize identification of these patients.[52] Walker et al noted that amongst a lung cancer cohort, those patients who were younger, with lower educational attainment, or with greater nicotine dependence were at higher risk of relapse.[16] These factors, along with male gender, depression/anxiety, and lower readiness to quit were identified as predictors of relapse in many of the included studies. These factors represent demographics that should be further explored in future interventional trials.

Amongst the studies that utilized interventions, very few were protocolized and, as a result, the impact of the intervention was often difficult to ascertain. Only one study addressed the efficacy of an intervention to prevent smoking relapse in patients who recently quit smoking after a cancer diagnosis, and demonstrated the intervention to be ineffective [13]. No studies directly assessed the utility of individual pharmacotherapy options or the intensity of behavioral therapy in preventing smoking relapse after a cancer diagnosis. These findings support the need for intensive maintenance tobacco cessation programs in the setting of a cancer diagnosis to prevent relapse.

Intensive tobacco cessation programs need not be expensive, nor time consuming for the patient. Some studies have demonstrated utility in addressing cessation during inpatient visits in the post-operative period [53–55]. Meanwhile, outpatient surgical clinic visits may represent an opportunity to decrease relapse rates, as pharmacotherapy continues to be underutilized amongst surgical specialists. In one study, only 12.7% of patients received nicotine replacement therapy, bupropion, or varenicline [56]. Another opportune time to reinforce tobacco abstinence may be during chemotherapy infusion visits. Future studies should consider optimizing an interventional approach that can be integrated into routine post-diagnostic visits. The Cancer Center Cessation initiative (C3I) represents a government-funded support program aimed at developing systems-based strategies to promote tobacco screening, cessation, and effect measurement programs [57].

Conclusions

Cancer diagnosis may serve as a “teachable moment,” inspiring patients to quit. However, sustainability of cessation is poor, with many patients continuing to smoke within months of the initial quit attempt at the time of diagnosis. Interventions may serve to improve abstinence rates and more intensive programs may improve efficacy of an intervention. Future study should aim to optimize post-diagnosis smoking cessation programs given the association between continued smoking and worse oncologic outcomes.

Supplementary Material

1

TABLE 6:

Association of Study Factors with Smoking Relapse Rate

Study Factor R2 Coefficient p
Average Age* 0.34 −3.47 0.003
Publication Year 0.06 1.03 0.24
Study Type 0.10 −18.73 0.12
% Female 0.05 −0.32 0.28
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*

statistically significant association

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