In this study, we analyzed SEER data to investigate the effect of gender on survival of patients who underwent primary surgical resection of RLPS. Our results revealed that men were associated with an increased risk of all-cause mortality, but not disease-specific mortality, after primary resection of RLPS in overall population. However, in patients with low-grade tumors, men were associated with increased risks of both all-cause mortality and disease-specific mortality after surgery. And these gender differences were more pronounced in patients who underwent non-radical surgery.
Given the rarity of the disease, no specific guideline for RLPS has been established yet. The most recent consensus was built by Trans-Atlantic RPS Working Group in 2015, focusing on the management of primary retroperitoneal sarcoma (RPS) in the adult. The consensus provided detailed perioperative management strategies of RPS, but did not cover the prognostic values of basic characteristics of the patients. Though increasing numbers of studies have suggested gender disparities may play important roles in cancer biology and prognosis, only few studies have examined the role of gender in the prognosis of RLPS. Moore Dalal et al built a nomogram to predict survival outcomes in 801 LPS patients, and gender was identified as a predicting factor for overall LPS4. However, the nomogram also suggested the primary site of LPS strongly affected the prognosis, and RLPS represented the worst subtypes4. Therefore, identification of the role of gender specifically in the prognosis of RLPS is necessary. The following studies only performed nomograms for patients with primarily resected or recurrent retroperitoneal sarcomas, and gender was not identified as one of the predictors of survival[12, 13]. The results of our study are clinically significant, for the sample size is the largest up to date and they fill the gap concerning the impact of gender disparities on the prognosis of RLPS.
In the overall population, we found men had a worse overall survival than women after primary resection of RLPS. Similar findings were also found in many other malignant tumors, for instance, melanoma, thyroid, non-small cell lung, gastric and hepatocellular cancers, etc.[14–18]. According to the SEER data, we found male LPS patients were generally older and had a higher proportion of high-grade tumors, which may lead to worse overall survival of male patients in the unadjusted analyses. However, we came to the same conclusion after we adjusted for age, histology, summary stages, tumor sizes, grade, and perioperative interventions. Regarding the potential reasons for survival benefits in women, a recent study found the age standardized rates for the majority of cancer types were greater in men than women in the 50 populations studied, which might suggest that at any given chronological age, the female tissues are physiologically younger than male tissues. Besides, other studies indicated that women’s benefits in overall survival may be attributed to women’s more responsive inflammatory functioning and men’s cardiovascular weakness[20, 21]. Future studies are necessary to further explore the underlying reason for the gender difference in the prognosis of RLPS.
In addition, several noteworthy findings emerged in subgroup analyses. First, as age is usually identified as an important predictor for survival, we tested whether the advantage of better overall survival still existed in elderly female RPLS patients. Our results revealed that the benefit of overall survival in women disappeared in the subgroup older than 70 years old, which might be explained by the equal susceptibility to surgical risks in the elderly patients. Second, surgical procedures seemed to be another interactive factor with gender in the prognosis of RLPS. We found the gender disparity of overall survival was more evident in the patients who underwent non-radical resection, while the survival benefit in women disappeared after radical surgery. This interaction effect may be caused by the strong effect of radical surgery on overall survival. Third, though no gender difference in disease-specific mortality was observed in overall population, subgroup analysis stratified by tumor grade indicated that men had a higher risk of disease-specific mortality than women in the subgroup of low-grade tumors with significant interactive effect. These findings may affect clinical practice by suggesting male RLPS patients with low-grade tumors should be treated and followed with a personalized strategy.
Some limitations existed in our study. First, our study was a retrospective study, subjective to information and selection biases. However, our study had a large sample size with long period of follow-up, which could provide sufficient information. Second, RLPS is characterized by high rate of local recurrence after primary resection, but the SEER database did not present details of recurrence during follow-up. As a potential substitute, the results of disease-specific death in this study might shed light on the tumor-related adverse outcomes. Third, SEER database did not report surgical margins, which prevented us from evaluating the potential confounding effect of resection completeness in survival outcomes. Fourth, French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading criteria for soft tissue sarcoma was not used due to lack of data, instead our study adopted histology grade of SEER database, which involved four categories: ‘Well differentiated; Grade I’, ‘Moderately differentiated; Grade II’, ‘Poorly differentiated; Grade III’, ‘Undifferentiated; anaplastic; Grade IV’. Though not as elaborate as FNCLCC grading criteria, our study could reveal an overall trend in the interaction between pathological information and gender on the prognosis of RLPS.