Table 3.

Recommendations on the theme ‘Host factors’ with relevance assessment

Recommendations from selected studies on ‘Host factors’ with relevance assessment.
Statement	Assessment
Smoking history should be equally reported in both male and female patients, because smoking status is an important potential confounder especially in lung cancer clinical trials.44	9
The gender-specific sensitivity of rectal cancer screening tests, gender differences in referrals, and clinical reasons for not prescribing preoperative radiotherapy in women should be further examined. If these gender differences are not clinically justifiable, their elimination might enhance survival.45	8
Further investigation of sex hormones and their association with the efficacy of cancer immunotherapy should be the focus of larger clinical trials to evaluate these parameters as possible prognostic markers.46	8
Subgroup analyses are important and should be conducted to provide evidence of sex-linked pharmacogenomic markers that should be further studied in larger cohorts of patients.47	7
Studies in a much larger sample of patients should be conducted to demonstrate more definitive trends in the clinical behaviour of oesophageal carcinoma between sexes.48	7
Further studies should be conducted to investigate the sex-dependent anti-tumour immune response to neoadjuvant chemoradiotherapy in patients with pancreatic ductal adenocarcinoma.49	7
The tumour microenvironment is closely associated with the clinical outcome of patients with ccRCC. Gender is one of the factors influencing the TII score. A high TII score seems to be more associated with the female sex.50	7

Recommendations promoted by the panel of experts on the theme ‘Host factors’ with relevance assessment.
Statement	Assessment
The number of lung carcinomas in nonsmoking women has increased in recent decades. In these cases, the aetiology should be clarified and the carcinogenicity of genetic factors, environmental exposures, and lifestyle should be investigated in a gender-specific manner, to change the study and management of lung cancer and to plan interventions to reduce the incidence of lung cancer in women.51	9
Genetic factors, some of which are sex related, and a number of modifiable environmental factors, including lifestyle, play an important role in the aetiology of colorectal cancer. Excessive body weight, poor nutrition, and physical inactivity are among the major risk factors for the development of this pathology, with a different impact in women and men. In primary prevention, protective diets and specific physical activity regimes for women and men should be considered.52	9
In women, the greater average length of the total and transverse colon, the more frequent occurrence of right colon cancer of flat type, and the narrower colon diameter than that of men can cause technical limitations of endoscopic examinations. Therefore a customisation of endoscopic devices for women should be carried out.53,54	9
In recent years, significant increases have been observed in the percentage of cases of NSCLC in males and patients >55 years of age. NSCLC pathogenesis research and prevention are urgently needed in these categories of patients.55	8,5
Young women with surgically treated NSCLC may have less comorbidity and have a lower percentage of postoperative complications. Despite the more advanced stage of the disease, survival is better than in older women. Therefore earlier and more effective diagnosis is needed in younger women who often have an advanced disease at the time of diagnosis.56	8
Gender behavioural differences in adherence to melanoma screening programmes and ultraviolet radiation skin protection have been demonstrated. These differences are also confirmed in patients who have already been diagnosed with melanoma: a greater percentage of women adopt behaviours that prevent the development of subsequent melanomas. More education and close follow-up examinations are therefore suggested, especially in male patients.57	8
After a diagnosis of melanoma women appear to have more favourable outcomes than men, as evidenced by longer free-time relapses and lower mortality rates. The skin of men and women differ in response to oestrogens and androgens. The first accelerate scar repair, increases the thickness of the epidermis, and exerts a protective action against so-called photoaging. Androgens, by contrast, can promote melanoma tumorigenesis. In addition, women have higher levels of immunoglobulins G (IgG) and M (IgM) antibodies and also so-called CD3+ T lymphocytes, a condition that makes them less vulnerable to the development of skin tumours. Men, by contrast, seem more susceptible to immunosuppression induced by ultraviolet radiation exposure. Gender is therefore an important prognostic factor for melanoma, for which specific primary prevention campaigns for women and men should be conducted and further studies should be carried out to include gender in the official melanoma staging system.58	8
Globally, the total incidence of skin melanoma is higher in men than in women, as well as differences in the anatomical localisation of melanoma. Studies recruiting a balanced number of men and women are needed to better understand gender differences and ensure gender-fair health care.59	8
Women with lung adenocarcinoma may have significantly better survival than men regardless of smoking habits. Other prognostic factors besides those known, such as access to treatments and therapeutic choices, should also be investigated.60	8
In addition to the scientific evidence regarding gender differences in skin melanoma, preliminary data suggest a different prognosis and a different clinical presentation between men and women also in uveal melanoma. However, they should be investigated through larger case series.61	8
In colorectal cancer hormonal factors seem to be responsible, at least in part, for the rate of incidence standardised by age which is higher in men than in women. Female sex hormones, in particular oestrogens, are protective factors, as evidenced by the increased risk found in postmenopausal women and the reduction of risk in postmenopausal women undergoing hormone replacement therapy. The possible protective role of oestrogen therapy in postmenopausal women with familiarity for colorectal cancer should be further investigated.62	7

ccRCC, clear renal cell carcinoma; TII, tumour immune infiltration; NSCLC, non-small-cell lung cancer.