Why does ovarian cancer have a poor prognosis

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Moreover, we failed to analyze the efficacy of radiotherapy and chemotherapy for patients with specific stage due to the unavailability of information from the SEER database. The impact of cycle and regimen of chemotherapy was not taken in consideration either. Although the patients with ovarian SCC may benefit from the current treatment, little improvement has been made in recent years, so it is vital to investigate novel agents and therapy.

The sequencing experiment that covered cancer-associated genes revealed that MCT-SCC had high mutation burden and shared similar mutation profile of lung SCC [ 17 ]. Considering the poor prognosis of this disease, early detection is of importance. In the present study, serum CA in prior to treatment was elevated in more than two thirds of the patients, which was in line with the previous reports [ 7 , 8 , 9 , 19 ].

Since ovarian SCC is often accidentally found at surgery, pretreatment measure of serum tumor markers may be useful for the early detection of this malignancy. These tumor markers are promising for preoperative diagnosis of ovarian SCC.

Regarding prognosis prediction, elevated CA was not a risk factor for worse outcome in the present study. Interestingly, the two large-scale reviews [ 7 , 8 ] demonstrated CA as a prognostic factor for MCT-SCC in univariate model, but did not examine its efficacy in Cox regression model.

For other ovarian cancers, it has been indicated that CA was a valuable predictor in univariate model but lost its significance when FIGO stage was considered in multivariate model [ 24 , 25 ]. So it is still controversial whether preoperative serum CA is an independent predictor for ovarian SCC outcome. The data is limited to America, information from the rest of the world are needed.

For example, there is no cohort for this specific rarity in China mainland, and such cases are sporadically documented in case report or case series [ 9 , 16 , 26 , 27 , 28 ].

Due to the low incidence of the disease, widespread collaboration across multiple centers may establish a cohort study with a relatively larger sample size. So there is still a long way to go before a national cohort of ovarian SCC is established. We hope this study could contribute to our current knowledge about this rarity by using the latest population database. Older age at diagnosis, advanced disease stage, larger tumor size and bilateral tumor are the independent risk factors for poor survival of ovarian SCC.

There are few information to provide guidance on the optimal therapy strategy. The behavior ICD-O-3 code was 3 malignant. Cases who were diagnosed from to were included. No other restrictions were imposed. The following variables were obtained from the database: patient ID, race, age at diagnosis, vital status, cause-specific death, survival months, laterality, grade, TNM stage based on 7th edition , SEER stage, surgical treatment, radiotherapy, chemotherapy, lymphadenectomy, tumor size and serum carbohydrate antigen CA prior to treatment.

Serum CA was recorded as elevated positive , within normal limits negative prior to treatment or test undone blank value. A total of 19, cases were selected. The flow diagram was shown in Fig. The detailed baseline information was shown in Table 3. Briefly for demographic features, more patients with SCC were not white, diagnosed at younger age and before than patients with SC were. For clinical characteristics, patients with SCC were more likely to be diagnosed with unilateral, lower FIGO stage, well-differentiated and localized malignancies than patients with SC were.

The optimum cut-off value for transformation of continuous variable into categorical variable was determined using X-tile software version 3. Univariate associations were analyzed using chi-square test for categorical variables or using Kruskal-Wallis test for ordinal variables. The Mann-Whitney U test was performed to identify significant difference in quantitative variable. Univariate and multivariate Cox regression analyses were used to evaluate the impact of variables on the OS and cause-specific survival of patients.

OS or cause-specific survival were defined as the time in months from diagnosis to death of any cause or specifically of ovarian SCC, respectively. The survival plot was made using Kaplan-Meier method and compared using breslow or log-rank test. All statistical analyses were performed with Rstudio version 1.

A p-value less than 0. Since the data was from national cancer registry project, no control over serous and SCC patients was assigned. Therefore, large differences on observed covariates in the two groups might exist.

Besides, since ovarian SCC is rare, there were a limited number of such patients and a much larger number of serous patients. Both of the two issues could lead to biased estimates. Matching is a common technique used to select control subjects and balance the covariates in the two groups.

In the present study, the propensity score for an individual, which considered many background covariates, was used for matching as a single scalar variable.

Here this score was defined as the likelihood of being ovarian SC predicted by a logistic regression model. The background covariates it considered were as follows: race, year of diagnosis, age at diagnosis, tumor size, laterality, FIGO stage, SEER stage and histological grade. Since the number of controls SC patients was huge, individuals were matched into SCC and SC groups, thus obtaining a larger sample size and a relatively more robust and powerful result.

The method was the nearest neighbor matching with a caliper of 0. No replacement was allowed, and patients were matched only once. Cancer statistics, CA Cancer J Clin. Article Google Scholar.

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We analyzed a database of patients presenting with advanced-stage ovarian, tubal or peritoneal epithelial carcinoma FIGO IIIC and IV with pleural invasion only treated in 7 French gynecologic oncology units from January to December [ 11 ]. All patients received optimal first line treatment involving a combination of platinium and taxane-based chemotherapy and curative debulking surgery.

Toulouse, Paris, Villejuif, Bordeaux, Nantes, Lille and Clermont-Ferrand institutional review boards granted permission for this retrospective and observational study. No written consent was given by the patients for their inclusion in the study. We stratified the population according to disease-free survival DFS. Patients who relapsed within the first 12 months constituted the early relapse group ER ; patients relapsing after 12 months were included into the late relapse group LR.

No relapse group NR corresponded to patients showing no evidence of recurrence after at least 36 months of follow-up. We excluded all the patients without relapse whose follow-up was less than 36 months. Recurrence was systematically assessed by conventional imaging computed tomography , PET scan or laparoscopic exploration. Therefore, isolated subsequent increase in CA level was not defined as a relapse.

Peritoneal carcinomatosis was quantified using the peritoneal index cancer PCI [ 12 ] and the extent of upper abdominal disease. Surgical procedures were sorted into 3 categories, according to the extent of resection [ 11 ]. Group 1 included standard procedures with hysterectomy, salpingo-ophorectomy, rectosigmoid resection, infra-gastric omentectomy, pelvic and para-aortic lymph node dissection and appendicectomy. Group 2 comprised all radical debulking surgeries. Group 2A patients underwent standard surgery plus routine upper abdominal procedure stripping of diaphragmatic peritoneum, splenectomy.

Group 2B consisted in ultra-radical surgeries involving a combination of digestive tract resections, organ resection spleen, bladder, stomach , coeliac lymphadenectomy and total abdominal peritoneum stripping, in addition to standard surgery. Regarding residual disease, patients were classified into 2 groups: no visible residual disease, and visible residual disease.

OS and disease-free survival DFS were computed as previously described [ 11 ]. The first-event corresponded to death of any cause for OS and to relapse or cancer-related death for DFS.

The Cox proportional hazard regression model was used for multivariate analysis. This previously described database was consistent regarding demographics, therapeutic management and outcomes with previous studies focusing on advanced-stage ovarian cancer. The median follow up time was 49 months. Mean DFS was Among our study population, patients One hundred fourteen patients Comparative demographics are displayed in Table 1.

Patients with ER had more poor prognostic factors. PCI, residual disease and stage IV rate were significantly higher than in the other groups. Noteworthy, no difference was found between ER and LR regarding treatment schedule and extent of surgery standard or radical procedures.

We performed a Cox logistic regression to determine the prognostic factors in ER group Tables 2 and 3. On bivariate analysis, mucinous histological subtype and grade 1 were associated with decreased OS HR of 4. Patients with no residual disease had significantly improved OS compared to patients with residual disease They also displayed increased OS after recurrence Concordantly, Kaplan Meier analysis did not show any difference in DFS according to residual disease status 8.

Within the ER population, complete cytoreduction was achieved in 79 women There was no statistical difference in treatment schedule between ER patients with complete resection and those with residual disease after surgery: rates of neo-adjuvant chemotherapy were respectively We did not observe any significant difference in recurrence sites and types isolated or multiple according to residual disease status, whereas we were expecting more peritoneal relapses in patients with tumor residues.

To determine if therapeutic modalities impacted prognosis, we compared the survival outcomes associated with the following patterns of treatment: 1 upfront standard surgery, 2 upfront radical surgery, 3 neoadjuvant chemotherapy followed by standard surgery and 4 neoadjuvant chemotherapy followed by radical surgery. We did not observe any significant difference in OS between all subgroups Fig 2. Among the ER group, 73 patients died within the first year following their relapse and constituted the poor prognosis PPER group.

OS after recurrence was 5. There were no differences between the 2 groups regarding stage, PCI, histological type and patterns of treatment and recurrence Table 4. The relative risk of death within 12 months following recurrence in ER patients was 1. The matching hazard ratio was 1. Despite the identification of inter-patient heterogeneity in prognosis among ER patients, the overall survivals associated with GPER group did not overlap with those observed in the LR patients: overall survival and OS after recurrence were significantly shorter in the GPER group In all centers, treatment modalities and schedule were defined in tumor review board and based on French and International guidelines.

Maximal surgical effort was performed to achieve complete cytoreduction with no tumor residue whenever applicable. Survival outcomes were homogeneous between the centers, except for one department that displayed increased OS Overall disease recurred in patients along the study period. The global rate of ER was thus Our study demonstrates that early relapses in advanced-stage ovarian cancer are not all doomed to a poor prognosis, as we have identified 2 subgroups with distinct survival profiles.

Within the early relapse ER patients, the absence of residual disease after surgery is the most important clinical prognostic factor. In the era of personalized precision medicine it is quite important to determine major clinical prognostic factors that will leverage our use of biomarkers. Early recurrence is perceived as a major factor of poor prognosis and treatment regimen is at this point chosen based on the timing of relapse rather than other considerations. Early relapses are usually considered as those occurring within 6 months after completion of first line treatment.

However, we consider this definition to be restrictive, mainly because clinical and radiological diagnosis may be delayed relative to the pathologic reality of the recurrence. Our aim was to focus on spontaneous prognosis after recurrence, regardless of second line treatments, and our analysis revealed no significant difference in outcomes after recurrence occurring within the first 6 or 12 months.

Therefore, we considered as early every relapse arising in the first year of follow-up.