A group of experts from AIIMS Delhi, McMaster University in Canada and the International Agency for Research on Cancer (IARC) in France has stressed the need to record smoking status in cancer clinical trials, warning that continued tobacco use can reduce treatment efficacy and patient survival.
In a commentary published in the Lancet Oncology this month, the seven authors, including Dr Abhishek Shankar from AIIMS Delhi, said knowledge of smoking status during therapy could influence clinical decisions.
They argued that addressing barriers to tobacco-use assessment and embedding smoking cessation initiatives into oncology research protocols will improve trial outcomes, enhance therapeutic efficacy and save lives.
The researchers cited the 2014 US Surgeon General’s report ‘The Health Consequences of Smoking — 50 Years of Progress’, which for the first time concluded there was a causal link between cigarette smoking and adverse cancer-related outcomes, including higher all-cause and cancer-specific mortality.
This report underscores the need to systematically capture smoking status in clinical trials, to refine estimates of efficacy of novel therapies and to better understand the impact of continued tobacco use across treatment modalities and disease sites.
Since 2014, research has increasingly shown that continued tobacco use negatively impacts patients receiving surgery, radiotherapy or systemic therapies.
The mechanisms by which tobacco smoke worsens outcomes remain unclear but may include tumour hypoxia, altered drug metabolism, stimulation of signalling pathways by nicotine and changes to the immune system, including reduced natural killer cells, the authors noted.
“Little is known about how best to overcome the effects of tobacco smoke, apart from cessation of tobacco use. Knowledge of smoking status during cancer therapy could potentially influence clinical decisions,” the authors said in the commentary.
They cited how the dose of erlotinib has to be doubled (from 150 mg to 300 mg daily) to achieve therapeutic concentrations in patients who continue smoking.
“These findings highlight a large gap in our understanding of how continued tobacco use might influence drug metabolism, therapeutic response and long-term outcomes,” the experts said, adding that the issue is most pressing in low and middle-income countries with 80 per cent of tobacco users.
Meta-analyses of lung, head and neck, hormone-responsive and other cancers show that quitting smoking after diagnosis results in longer survival, with early quitting offering the greatest benefits. The authors stressed that the survival advantage of quitting could even exceed the impact of the therapy under investigation.
They also cautioned that failure to collect smoking data risks confounding trial results, especially if treatment groups are unbalanced for tobacco use.
The commentary pointed out that the 2020 US Surgeon General’s report recommended structured cessation efforts as standard cancer care, though it said more data was needed to confirm a causal link with improved survival.
The authors referred to a 2020 US FDA–AACR–IASLC workshop which addressed the importance of tobacco-use assessment in oncology trials. Despite such efforts and published evidence, clinical trials still rarely incorporate robust tobacco-use assessments, they said.
Absence of standardised tools and protocols for assessing tobacco use leads to inconsistencies in data collection, making it challenging to compare results across studies, authors added.
They further said that some researchers and clinicians might perceive tobacco use as having minimal impact on clinical outcomes, leading to its omission from data collection.
“However, evidence strongly suggests that continued tobacco use can have a substantial adverse effect on cancer treatment efficacy and patient survival,” the authors said.
They also said that opportunities to intervene with current users after diagnosis have been missed, and more research is needed on mechanisms by which tobacco worsens outcomes.
Collecting detailed smoking data requires time and resources, which might be limited in clinical trial settings, they pointed out. Electronic health record systems might not have integrated templates for recording smoking status information, leading to inconsistent documentation.
The absence of automated prompts or referral systems can further impede the collection of accurate tobacco use data, the doctors said, adding that pharmaceutical manufacturers might perceive smoking status assessments as a threat.
If smoking diminishes a drug’s efficacy or exacerbates side-effects, it could negatively impact regulatory approval and market size, they added.
Referring to a 2024 study by Cincirpini and colleagues, they said cessation support should ideally be provided within six months of diagnosis to observe the greatest survival benefit. With e-cigarette use rising globally, their use should also be captured in trials, though their impact is likely to be less severe than active smoking.
In the past decade, many cancer centres in Canada, Australia and the US have made smoking cessation discussions standard practice at the time of patient registration, with advice and referrals offered.
In 2023, the IASLC’s Tobacco Control and Smoking Cessation Committee also issued a position statement declaring smoking status capture as a key standard for clinical trial design.
“Capturing smoking status in clinical trials should no longer be considered optional; it should be regarded as an essential core element of cancer research,” the authors concluded.