Evidence
Alert

Women with cancer of the stomach or oesophagus are more likely to survive than men, but they have worse side effects from chemotherapy

Women treated for cancer of the stomach or oesophagus (the muscular tube which moves food from mouth to stomach) may survive longer than men. An analysis of over 3000 patients with these cancers also found that women experienced more nausea, vomiting, and diarrhoea during therapy.

Cancer-related survival was the same for older (70 or over) and younger patients.

The study set out to examine how a patient's age and sex influence their survival from these common cancers, and the side effects they experience. The findings could help tailor the management of individual patients' treatment. They highlight those more at risk from specific side effects and suggest ways to help minimise the impact.

What’s the issue?

Almost 16,000 people each year in the UK are diagnosed with cancer of the oesophagus and stomach. The standard treatment for localised tumours is chemotherapy followed by potentially curative surgery. But it is not clear how a patient’s age and sex influence the side-effects they experience and their survival post-operation.

Doses of standard chemotherapy drugs are based on data gathered from trials carried out mostly on men. But women may have a different response to chemotherapy which means that they experience worse side effects than men.

More data on how biological differences between patients influence their response to treatment would help doctors to tailor the most appropriate treatment to individual patients. This is part of a move to introduce personalised medicine. It would also help identify those who are more likely to experience side effects during chemotherapy, and allow them to be prepared as far as possible.

Some doctors are more reluctant to recommend chemotherapy and surgery for older patients, because they consider them frail and more vulnerable. But this belief had not been tested before this study.

What’s new?

This meta-analysis pooled and compared data from 3265 patients - 2668 men and 597 women – who received chemotherapy for cancer of the oesophagus and stomach, followed by surgery to remove the tumours. The researchers looked at how long patients survived and what side effects they experienced during chemotherapy.

The results showed:

  • women were significantly more likely to experience gastrointestinal symptoms such as nausea (10% versus 5% in men), vomiting (10% versus 4%) and diarrhoea (9% versus 4%)
  • other side effects occurred similarly in women and men. They included tinnitus (hearing noises from inside your body), loss of taste, fever and infections
  • women survived 28.6 months after surgery, an average of five months longer than men (23.7 months)
  • age (under or over 70) made no difference to cancer-related survival
  • older people were more likely to have reduced immunity (neutropenia) which makes them vulnerable to severe infections.

Younger patients (under 70) were more likely than older patients to complete the planned chemotherapy course than older patients; and men more likely than women. Despite this, all groups saw similar rates of tumour response. This suggests that women and older patients may be successfully treated with lower doses of chemotherapy.

Why is this important?

Cancers and cancer treatment can affect people in different ways, but it is difficult for doctors to tailor therapies because of a lack of data on the likely benefits. The new findings show that women tend to survive for longer after treatment. This adds to the growing evidence that sex differences can be significant in cancer.

The results also show the benefits of stratifying clinical trials - and of interpreting existing trial data – by sex. Men and women respond to the same treatment differently, and the results from a mixed sample could be misleading. Regulators could ask for data on sex differences in sensitivity to side effects when they assess possible new chemotherapies. At present, most data on appropriate chemotherapy dose comes from men.

The finding that over-70s do as well as younger patients when given combined treatment of chemotherapy and surgery show all ages should be offered the same options, depending on individual health and fitness. It’s important to note that the over-70s in this study, beyond their diagnosis of cancer, were relatively fit and healthy. The results might be different in older patients who also suffer from other medical conditions.

What’s next?

Because women experience more severe side effects from chemotherapy, the results suggest it would help to warn them in advance and offer education or counselling about what to expect. The disparity in survival rates and side-effects by sex (and the lack of difference by age) can help clinicians plan treatment and plan for likely outcomes.

The scientists plan to follow this study by analysing tissue samples taken from patients in the trials in the review. They will explore whether samples from men and women show differences at the molecular level (such as in the DNA and RNA). These differences could explain why women suffer from this type of cancer less often than men and why they do better after treatment.

This could help researchers better understand why different people react differently to the same cancers and the same treatments. It has been shown that patients who carry variants of one particular gene (called DPYD) may be particularly likely to have a bad reaction to a common chemotherapy drug called fluoropyrimidine. Some doctors already give different doses of this chemotherapy depending on a patient’s genetic makeup.

You may be interested to read

The full study: Athauda A, and others. Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03). European Journal of Cancer. 2020;137:45-56

A video illustrating the study findings

Funding

The study was funded by the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research London.

Commentaries

Study author

We tend to use a standard treatment approach for managing oesophageal and stomach cancers. But this research suggests significant differences between male and female patients. I don’t think that’s surprising because we know that women tend to do better in cancer in general.

The finding that older patients do as well as younger patients is very reassuring because it means we can treat them in the same way, as long as they are fit enough. I think that’s one immediate lesson for clinicians.

Avani Athauda, Clinical Research Fellow, The Royal Marsden NHS Foundation Trust

Member of the public

Oncologists and surgeons treating patients should be aware of differing toxicities and dose responses to chemotherapy experienced by men and women, and that women may benefit from more personalised intervention.

The study should also reassure clinicians that fit older patients can be safely managed with the same curative regime as younger ones.

The paper should promote further research into the delivery of personalised chemotherapy. It also demonstrates that sex is a readily available, cost-free, biological variable that should be incorporated into clinical trials of chemotherapy.

Ruth Hayes, London

Oncologist

The paper in itself will not change current clinical practice. Patients will continue to receive the same treatment in the same way but with the knowledge that women are more likely to have a better outcome.

There were no significant differences in outcomes between younger and older patients. This should encourage clinicians to treat the older population. Specialist input from geriatricians when making treatment decisions may improve uptake in this group.

A point to note was the imbalance of male and female patients recruited into these large trials. In the UK about 35% of patients with gastric cancer are female, compared to only 20% of patients in this pooled analysis. This should encourage national efforts to recruit women into clinical trials.

Asad Qureshi, Consultant Clinical Oncologist, Guy’s and St Thomas’ NHS Foundation Trust, London

Conflicts of Interest

Several study authors received funding from various pharmaceutical companies.