This is the first study to focus on the impact of pregnancy on the prognosis of UM patients treated with PBT and that based on Chinese population. Also, we were the first to discuss weather UM or PBT treatment has any effect on the physiology process of pregnancy and its outcome.
Above all, our results show that the survival and metastasis rates of these patients is similar to that of women of childbearing age who had no pregnancy after treatment. This result is consistent with the absence of estrogens and progestogens in UMs(11, 16–18). The only two previous clinical studies(13, 14) which focused on pregnancy occurred after the treatment of UM also supports our findings. Similar to our report, both studies treated most their patients with conservative treatment primarily such as proton beam irradiation or brachytherapy. Therefore, These findings of similar prognosis among patients who had or didn’t have children after PBT may also be the result of the cessation of mitotic activity and tumor cell necrosis in most patients after local radiotherapy(19).
However, there have been occasional cases of significantly increased UM during pregnancy over the past few decades(16, 17). Lee et.al reported a 31-year-old woman with a 29-week pregnancy was diagnosed with uveal melanoma(17). She refused any treatment for the remaining three months of her pregnancy and the tumor increased in size from 8×5 mm2 to 13×12 mm2. Recently, Yue et.al. reported the first Chinese case of accelerate growth of UM during pregnancy and the tumor showed a rapid growth rate and extended to the orbit with muscle invasion. Similar to the previous case, the patient did not receive any treatment before the end of pregnancy, also there was no detailed medical report but only the subjective feelings of the patient prior to pregnancy. Combining previous retrospective case-control studies and reports of these two cases, we suggest that UM patients treated with local radiation therapy is probably unaffected by hormonal and ocular physiological changes during pregnancy.
Also, similar to some previous studies, we demonstrated that UM had no significant impact on maternal fertility for there had been hundreds of cases reported of UM discovered during pregnant and UM patients getting pregnant(11, 14, 16, 20–22). Among all these reports, including our own, and the vast number of cases that they have reported, we found only one case report of placental metastasis attributed to choroidal melanoma(23), and none fetal metastasis. Therefore, we can draw a preliminary conclusion that it is extremely unlikely for choroidal melanoma to metastasize to fetus. Additionally, we also proved that the plaque brachytherapy with localized radiation also has neither significant effect on maternal fertility, nor teratogenic effect on the fetus.
Some limitations of this study should be also noted. First of all, like previous studies, the number of pregnant cases in this study was limited. UM is a rare disease with most patients presenting between the ages of 50 years and 70 years(1). It is estimated to have an incidence rate of four to eight per million, with a reported higher rate among men(2, 24). Therefore, few women of childbearing age have a history of uveal melanoma. Additionally, although survivors of non-reproductive organ cancer had similar birth rates as the background population(8), in clinical practice, many patients gave up the idea of having children upon diagnosis of malignant tumor. These factors have limited the number of cases in studies of pregnancy in UM patients after treatment. Secondly, according to follow-up, gross examination of the placenta did not show any evidence of metastatic disease, and since none of the pregnant patients gave birth in our hospital, none of the specimen underwent microscopic examination. We believe that pathological examination of the placenta should be performed as described by previous study(23) to accurately exclude placental metastases.
In the past 20 years, few articles have focused on this issue, and we hope to attract researchers' attention to women of reproductive age with malignant tumors. Further clinical and basic studies are needed to draw more definitive conclusions.