Gender-Related Approach to Kidney Cancer Management: Moving Forward

Abstract

Men are more frequently diagnosed with kidney cancer than women, with a more aggressive histology, larger tumors, a higher grade and stage, and worse oncological outcomes. Smoking habits and sex steroid hormones seem to have a possible role in explaining these gender disparities. Moreover, the expression of genes involved in tumor growth and immune response in kidney cancer varies between men and women, having an impact on the gender-related response to oncological therapy, such as anti-angiogenic drugs and immunotherapy. Recent advances have been made in our understanding of the molecular and genetic mechanisms involved in kidney cancer, which could partially explain the gender differences, and they are summarized in this paper. However, other key mechanisms, which fully clarify the striking clinical gender-related differences observed in kidney cancer, are not completely understood at present. We reviewed and summarized the most relevant publications about the relationship between gender and kidney cancer. Efforts should be made to progress in bench and clinical research on gender-related signatures and disparities, and their impact on the clinical management of kidney cancer.

The Current Evidence for Factors that Influence Treatment Decision Making in Localized Kidney Cancer: A Mixed Methods Systematic Review

“…Being black and/or female has been found to be associated with higher use of RN 13 , despite the fact that this ethnic group is at higher risk of chronic kidney disease progressing to endstage renal disease 57 . In support of this finding, Mancini et al found that gender influences treatment option selection and identified that men were more likely to receive AS or NSS treatments 58 . This further supports the findings of our review that potential indirect barriers are linked to demographic factors including race and gender and due to the current observation design of the studies, we recommend that future studies need to further investigate how demographic factors like age and gender influence choice.…”

Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence

“…Surprisingly, in metastatic RCC patients, female sex had a significant independent association with death (HR 1.19) [137]. Mancini et al, reported that disease recurrence seems not to be different among males and females, with the latter showing a more favorable prognosis after recurrence [105]. Wood et al, showed that male sex, a solitary kidney at partial nephrectomy, positive surgical margins, multiple tumors and higher nephrometry score and pathological stage increased the risk of local tumor bed recurrence [161].…”

“…Namely, females tend to develop less likely pRCC while are more frequently diagnosed with chromophobe RCC than males. This difference may be clinically important, as it might partially explain the more favorable outcomes of RCC among females (considering the less aggressive behavior of chromophobe RCC) [12,105,116]. A recent Japanese retrospective study confirmed these findings [127].…”

“…More than 50% of RCC are detected incidentally by non-invasive imaging performed for a variety of nonspecific symptoms and/or other abdominal concerns. In this regard, previous studies have shown that male patients may be significantly younger than female patients at the time of diagnosis, raising the hypothesis of a potential protective role of female hormones at younger ages [40,105].…”

Sex and Gender Influences on Cancer Immunotherapy Response

“…Two studies showed a strong association between female gender and psychological distress linked to kidney cancer [ 141 , 142 , 143 ]. A link between psychological factors, stress and cancer is recognized, and recently Inderberg and Wälchli highlighted the influences on molecular mechanisms taking place during T lymphocytes priming and cancer vaccination of ourpsychological status [ 144 ].…”