Clinicopathological Characteristics And Analysis For Prognosis Of Patients With Endometriosis Associated Ovarian Cancer

BackgroundEndometriosis(EMT)is a common and serious threat to a woman’s quality of life and fertility function in reproductive-age women.It is usually considered a benign disease but has characteristics similar to malignant tumors,such as invasion,adhesion,and metastasis.More studies have shown that EMT have some malignant potential,with approximately 0.7%-1%of patients at risk of malignancy.Epidemiological and molecular genetic studies continue to show that endometriosis is closely related to epithelial ovarian cancer(EOC),especially ovarian clear cell carcinoma(OCCC)and ovarian endometrioid carcinoma(OEC).Therefore,a group of epithelial ovarian cancers that are histologically closely related to endometriosis and may arise malignantly from endometriosis,with ovarian clear cell carcinoma and ovarian endometrioid carcinoma as the main pathological types,is called endometriosis-associated ovarian cancer(EAOC).It is considered a special type of ovarian cancer and EMT have been regarded as a precancerous lesion of OCCC and OEC due to different clinical characteristics and prognostic manifestations.Considering the large patient base of EMT and their long time window for malignant transformation,EAOC should draw our attention enough.In clinical practice,it is often the case that clinical history is not collected,a strict follow-up plan is not established for patients at high risk of EMT malignancy,and pathologists miss EMT lesions coexisting with ovarian cancer because they are not sufficiently alert to EAOC,thus affecting the early detection,stratified management and precise treatment of patients.Many clinical studies currently have less stringent diagnostic criteria for EAOC,using category C of the Van Gorp classification,or even using ovarian cancer with a history of self-reported EMT as diagnostic criteria.This results in highly biased,subjectively influenced studies,and considerable variability between studies.Meanwhile,EAOC lacks clear exclusion criteria,i.e.,non-endometriosis associated ovarian cancer(n-EAOC)diagnostic criteria.Due to the growth,infiltration,and destruction of cancer lesions,their originally malignantly derived EMT lesions may not be visible in pathological sections,so even if no EMT lesions are seen in the sections,the possibility of EAOC cannot be completely excluded.The pathogenesis of EAOC is still unclear and there is a lack of reliable biological markers for diagnosis,so there is no basis and target for stratified management and precise treatment.Whether EAOC is a specific ovarian cancer entity or just an intermediate link in the progression of ovarian cancer needs to be further investigated,and whether the origin of EMT is a better prognostic factor for ovarian cancer is controversial.These problems pose a great challenge for the management and treatment of EMT malignancy and EAOC.ObjectivesTo investigate the clinicopathological and prognostic characteristics of EAOC patients.To analyze the factors affecting their prognosis and the predictive value of related factors for death or recurrence in patients with OCCC and OEC.MethodsA total of 250 patients with primary ovarian cancer,hospitalized for surgical treatment and with postoperative pathology confirmed as OCCC or OEC,who visited the Department of Gynecology,Qilu Hospital,Shandong University from January 2005 to December 2021,were included in the study.Two senior pathologists reviewed the pathological sections of the patients and divided them into 71 cases in the EAOC group and 179 cases in the n-EAOC group according to the criteria of cancerous tissue co-existing with EMT in the ipsilateral ovary(i.e.category A and B in the Van Gorp classification).To retrospective analysis and compare the clinicopathological and prognostic characteristics of the two groups and their subgroups in different pathological types.Cox univariate and multifactorial risk regression analyses were performed to clarify the factors affecting disease free survival(DFS)and overall survival(OS)in patients with OCCC and OEC,and to analyze the predictive value of the corresponding factors for recurrence or death in patients with OCCC and OEC.ResultsCompared to patients in the n-EAOC group,patients in the EAOC group were younger(mean age of onset 47.49±9.42 years vs 53.46±11.08 years,P<0.001),most patients were premenopausal(61.97%vs 38.55%,P=0.001),most patients had a previous history of dysmenorrhea(55.74%vs 29.63%,P<0.001),fewer births(80.28%vs 59.55%for ≤1 birth,respectively,P=0.002),earlier age at menarche(42.19%vs 26.85%for age at menarche≤13 years,respectively,P=0.027),shorter menstrual cycles(median menstrual cycle 28 days vs 30 days,P=0.029),lower serum carbohydrate antigen 125(CA125)levels(median CA125 level 81.95U/mL vs 207.00U/mL,P=0.001),lower serum carbohydrate antigen153(CA153)level(median CA153 level 14.52U/mL vs 21.95U/mL,P=0.002),lower blood neutrophil to lymphocyte ratio(NLR)(median NLR level 2.18 vs 2.76,P=0.006),lower fibrinogen(FIB)level(median FIB level 3.27g/L vs 3.89g/L,P=0.003),lower D-Dimer(D-Di)level(median DDi level 0.18ug/mL vs 0.54ug/mL,P<0.001).Also,patients in the EAOC group had more unilateral distribution of tumors compared to patients in the n-EAOC group(87.32%vs.72.07%,P=0.010).Fewer patients with combined ascites in the EAOC group(22.54%vs 68.97%,P<0.001).The tumors in the EAOC group had earlier International Federation of Gynecology and Obstetrics(FIGO)staging(P<0.001),lower Ki-67(P=0.044)and WT-1(P=0.010)expression.More patients in the EAOC group achieved satisfactory tumor reduction with surgery(91.55%vs 76.97%for complete resection rate of all visually visible lesions,P=0.009),more patients with combined adenomyosis(28.36%vs 15.48%,P=0.023),and fewer tumors showed drug resistance(10.77%vs 27.04%,P=0.023).Most of them showed similar characteristics in OCCC and OEC subgroup analysis.Compared with n-EAOC group,patients in the EAOC group had lower recurrence(16.18%vs 33.11%,P=0.001),lower mortality(11.43%vs 27.49%,P=0.013),higher 2-year disease free survival(85.60%vs 70.30%,P=0.024),higher 2-year survival(94.70%vs 83.40%,P=0.011),longer DFS(P=0.017),and longer OS(P=0.049).Similar characteristics were shown in OCCC and OEC subgroups,but the differences lacked statistical significance in the OEC subgroup.Cox univariate and multifactorial analyses of DFS and OS in patients with OCCC and OEC show that pregnancy(P=0.002),FIGO stage(P=0.013),and chemotherapy resistance(P<0.001)are independent risk factors for DFS and chemotherapy resistance(P<0.001)is independent risk factor for OS in patients.Cox univariate and multifactorial analyses of DFS and OS in the OCCC subgroup of patients,respectively,showed that FIGO stage(P<0.001),outcome of decompression(P=0.036)and chemotherapy resistance(P<0.001)were independent risk factors for DFS,and combined adenomyosis(P=0.025)and chemotherapy resistance(P<0.001)were independent prognostic factors for OS.Originating from endometriosis had no significant effect on PFS and OS in OCCC and OEC patients(P>0.005).Conclusions1.Patients in the EAOC group are younger,more in premenopausal status,more with a history of dysmenorrhea,earlier age at menarche,shorter menstrual cycles,fewer births,lower serum CA125,CA153,and NLR levels,more combined adenomyosis,less combined ascites,more unilateral distribution of tumors,earlier FIGO stage of the tumor,more surgically achievable R0,and fewer chemotherapy-resistant than in the n-EAOC group.2.EAOC patients had a better prognosis than n-EAOC patients,but origin of endometriosis was not an independent prognostic factor for OCCC and OEC patients.3.In patients with OCCC and OEC,pregnancy,tumor FIGO stage,and chemotherapy resistance were independent risk factors for DFS,and chemotherapy resistance was an independent risk factor for OS.In patients with OCCC,FIGO staging,decompression results,and chemotherapy resistance are independent risk factors for DFS,and combined adenomyosis and chemotherapy resistance are independent prognostic factors for OS.