Pseudomyxoma peritonei (PMP) is a rare clinical syndrome that occurs with an incidence of 2 cases per 100 million individuals (1, 2). Most PMP arise from perforation of a primary appendiceal cancer and seeding of tumor cells within the peritoneal cavity (3). The gold standard curative treatment for PMP is complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CCRS/HIPEC) (4, 5).

The majority of women with PMP have involvement of the ovaries due to direct invasion from the adjacent appendix or redistribution of PMP within the peritoneal cavity (6, 7); therefore, ovariectomy is often recommended. However, surgical menopause occurs after bilateral ovariectomy. This can have a negative impact on patient quality of life, especially in young women who wish to have children. There remains an unmet clinical need for effective strategies that preserve fertility in young women with PMP of appendiceal origin and to build consensus on management in cases where the ovaries appear normal during CRS. The objective of this study was to determine prognosis for female patients with PMP of appendiceal origin and unilateral or bilateral ovaries preserved during complete cytoreductive surgery (CCRS). Findings will inform clinicians who manage women with PMP.

PMP is a clinical entity characterized by mucinous ascites, peritoneal soft-tissue implants, omental caking, and involvement of the gastrointestinal tract and ovaries. A distinguishing feature of PMP is its redistribution within the peritoneal cavity determined by normal flow of peritoneal fluid and gravity. In the present study, among the 963 patients with PMP who were treated at the Aerospace Center Hospital, Beijing between January, 2009, and December, 2019, 92% of patients had PMP of appendiceal origin. This rate is consistent with previously reported case series of patients with PMP treated with CRS/HIPEC, among which 89.6%–94% of patients with PMP had a primary appendiceal tumor (8–10). In other patients, PMP may originate from a tumor in the ovary, colon, small bowel, urachus, pancreas, bile duct, stomach, uterine cervix, fallopian tube, mesentery, kidney, extraovarian teratoma, or spleen.

In females, PMP of appendiceal origin usually metastasizes to the peritoneal surface of the ovaries and the uterus. At our center, the probability of ovarian involvement was 74.8% (119/159). A total hysterectomy with bilateral salpingo-oophorectomy may be recommended, regardless of pre-operative gynecologic organ involvement. However, young women may wish to avoid the associated iatrogenic surgical menopause and permanent infertility (11), which can have major psychosocial consequences and a negative impact on the quality of life of the patient and her family. In the present study, there was a significant difference in age between patients who chose to preserve their ovaries during CRS and those who underwent ovarian resection, with younger patients more likely to choose ovarian preservation.

Among the 19 patients with PMP of appendiceal origin and unilateral or bilateral ovaries preserved during CRS included in our study, 6 desired to have children. At the end of follow-up, only one patient was planning to undergo in vitro fertilization. Our findings showed that PMP recurrence rates rose rapidly two years post-CRS, implying that women who underwent CRS with/without HIPEC for PMP with ovarian preservation should attempt to conceive as soon as possible when the recommended waiting period following therapy is complete (12, 13).

In other literature, two small retrospective studies and 5 case reports have investigated the feasibility of ovarian preservation in patients with PMP of appendiceal origin (14–20). One study in four women aged 28–35 years with PMP who sought to maintain fertility adopted a strategy that involved laparoscopy for disease staging followed by appendicectomy, irrigation of the abdominal and pelvic cavity with water, and stripping of macroscopic disease from the peritoneal surface of the pelvis and the surface of the ovaries. All patients had a low-grade appendiceal mucinous neoplasm with acellular mucin or LG-MCP in the peritoneal cavity. After the procedure, all patients conceived and gave birth to healthy babies. After 12–29 months of follow-up, all women were well with no evidence of disease recurrence on radiology or laparoscopy (21). Other women have conceived following treatment with CCRS + HIPEC. In one study, women aged <41 years with peritoneal carcinomatosis of various origins who expressed a strong desire for future pregnancy were treated with CCRS + HIPEC. At least one ovary was preserved in 21 women. Of these, 4 women developed ovarian recurrence after a median follow-up of 32 months, and two women became pregnant (14). An international survey reported seven pregnancies in women with PMP, epithelial mesothelioma, or papillary mesothelioma who underwent genital organs-preserving CRS and HIPEC, with delivery of seven newborns. Bilateral ovaries were preserved in 5 women, the left ovary was preserved in one woman, and ovocytes were harvested and cryopreserved in one woman. All women were disease free at 42–106 months of follow-up (15). In a case study, a 28-year-old patient with PMP underwent CRS + HIPEC. Bilateral ovaries were preserved, and the woman spontaneously conceived 14 months after surgery. The pregnancy was uneventful (16).

In our study, among all patients, median OS was 71 months (range, 54–88 months), and the 5-year survival rate was 37.9%. In a previous retrospective study of 2,289 patients from 16 specialized units who underwent CRS for PMP, 10- and 15-year survival rates were 63% and 59%, respectively, treatment-related mortality rate was 2%, and major operative complications occurred in 24% of patients (22). In another study of 42 patients who underwent CRS + HIPEC, 5-year survival rates after first and second CRS were 75.5% and 67.7%, respectively (23). In the present study, the incidence of serious complications and mortality rate was acceptable, but 5-year survival rate was comparatively low, potentially due to the distribution of pathological types. In the ovarian preservation group, 47.4% of patients had HG-MCP, which is associated with a poor prognosis. The ovary is a reproductive and endocrine organ that has a rich blood supply, which may promote tumor growth and metastasis. Consequently, we recommend ovarian resection during CRS in patients with HG-MCP. Meanwhile, the limitations section of our study provides context around our patient population, stating that the majority of patients were transferred to our institution from a local hospital in poor general condition, which increased their risk of mortality. Patients in this study were treated with CRS with or without HIPEC, and patient’s care goals, personal values, and wishes were incorporated into HIPEC decision-making. We believe that this treatment pathway is representative of the clinical situation in the real world.

In our study, among all patients, median DFS was 22 months (range, 12–32 months), and the 5- year recurrence rate was 87.4%, which are higher than reported elsewhere (24). Disparate findings between the present study and previous findings may be explained by differences in the patient populations. We included patients with LG-MCP or HG-MCP, while the previous report focused on patients with LG-MCP. Median DFS among our patients with LG-MCP was 32 months (range, 15–49 months), and the 5-year recurrence rate was 75.0%, which were comparable to the previous report. The present study was conducted at a referral center for myxoma, which may have led to selection bias favoring patients with more severe disease. Most notably, PMP is a rare disease; therefore, small sample size may have affected our findings.

In our study, there was no significant difference in OS in patients with LG-MCP or HG-MCP, whether ovariectomy was performed or not; however, in patients with LG-MCP, median DFS was significantly longer in patients with ovarian resection compared to ovarian preservation This suggests that ovarian preservation may increase risk for disease progression, but has little effect on the final prognosis of the patient. On multivariate analysis, high-grade histopathologic subtype of PMP was an independent predictor of poor prognosis (OS and DFS). This may be related to the growth pattern of the tumor cells and ovarian retention. Ovarian involvement is correlated with the peritoneal extent of PMP and tumor grade. Previous studies showed higher rates of ovarian invasion in patients with grade 2–3 PMP (25); specifically, 62% of ovaries were invaded in patients with grade-1 PMP, and 87.5% of ovaries were invaded in patients with grade 2–3 PMP (26). Other studies confirm these findings (27–30). Interestingly, in our study, neither PCI nor the use of HIPEC were independent predictors of prognosis. This may indicate that radical resection is more important than tumor burden and HIPEC in influencing prognosis.

This study was associated with several limitations. First, this was a retrospective study, and several clinical and histopathological data were lacking, such as the histology of the resected ovaries and intravenous chemotherapy regimen. The two groups were not homogenous to some extent. Second, most patients were transferred to our institution from a local hospital in poor general condition, which increased their risk of mortality. Last, the follow-up time was not long enough, especially for patients with preserved ovaries. Further large-scale studies are needed to confirm our results.

In conclusion, histopathologic subtype of PMP represents an independent predictor of prognosis in female patients with PMP of appendiceal origin and unilateral or bilateral ovaries preserved during CRS. These findings imply that ovarian preservation is a more suitable option for young females with low-grade PMP compared to high-grade PMP. However, the reported data were very limited and further prospective studies should be done investigating the role of resection of uninvolved ovaries in PMP.