"The impact of debulking surgery in patients with node-positive epithelial ovarian cancer: Analysis of prognostic factors related to overall survival and progression-free survival after an extended long-term follow-up period".

OBJECTIVE: to estimate the prognostic factors associated with survival and progression free survival (PFS) in patients with node-positive epithelial ovarian cancer (EOC) after an extended long-term follow-up period. METHODS: Data was provided by the Tumor Registry of the Mayo Clinic, Scottsdale, Arizona on 116 node-positive EOC patients who underwent primary cytoreductive surgery observed over the period 1996-2014. RESULTS: At censoring date, 21 patients were alive (18%), 95 dead (82%), 18 without evidence of disease (NED) (15 alive, 3 dead) and 76 with evidence of disease (ED) (2 alive, 74 dead). Twenty-nine ED patients (38.2%) experienced a recurrence within 2 years, 53 patients (69.7%) before 5 years. No recurrences were recorded after 10 years. The median follow-up in alive patients was 169.8 months (1.20-207.9 months), 34.9 months (0.30-196.2 months) in dead patients, 128.4 months for NED patients (72.8-202.5 months) and 34.6 months (0.1-106.9 months) in ED patients. Multivariate analysis showed an increased risk of dead in patients with age ≥ 60 years (HR: 3.20; p < 0.002), stage IVA/B (compared with stage IIIA1/2, HR: 4.31; p < 0.001 and stage IIIB/C, HR: 5.31; p < 0.010) and incomplete surgery (compared with complete surgery, HR: 3.10; 95% CI, 1.41-6.77; p < 0.003) and a decreased PFS in stage IVA/B (compared with stages IIIB/C; p = 0.003 and stage IIIA; p = 0.000) and residual volume after surgery >0.6 cm (compared with residual disease <0.5 cm; p < 0.023). CONCLUSIONS: prognostic factors for an extended long-term PFS are similar as those for survival, because after 17-year follow-up period, the majority of alive patients are NED patients.

Peritoneal carcinomatosis: A malignant disease with an embryological origin?

INTRODUCTION: In 1931, Simpson et al. coined the term "peritoneal carcinomatosis" to describe the regional spread of ovarian tumors as localized or extended with involvement of the peritoneal serous membrane and neighboring anatomical structures. Research into the origin of peritoneal carcinomatosis is based on two phases in a woman's life: EMBRYO DEVELOPMENT: During week 3, the bilaminar disc becomes a trilaminar disc called the mesoderm. Inside the lateral plate mesoderm, the coelomic cavity is divided into 2 layers: the parietal (somatic) mesoderm, which gives rise to the parietal peritoneum and pleural surfaces; and the visceral (splanchnic) mesoderm, which gives rise to the visceral peritoneum, visceral surface of the pleura, gonadal stroma, and the muscular layer of the hollow viscera and its mesenteries. TUMOR SPREAD: Transcoelomic metastasis and metaplasia of pluripotent stem cells in the peritoneum was involved in the pathogenesis of ovarian cancer. This involvement takes the form of a synchronous malignant transformation at multiple foci and may cause intraperitoneal field cancerization. Pluripotent stem cells play a role both in the development of the embryonic peritoneum and in the spread of transcoelomic tumors. Consequently, knowledge of the origin of these cells (embryonic or current) could be extremely useful. The many markers that act during the embryonic period can affect descendants, that is, cells are already marked before specification and differentiation are activated. Thus, programmed activation could be attributed to genetic and epigenetic changes.

International Federation of gynecology and obstetrics staging classification for cancer of the ovary, fallopian tube, and peritoneum: estimation of survival in patients with node-positive epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to determine the survival of patients with node-positive epithelial ovarian cancer according to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. MATERIALS AND METHODS: We performed a retrospective chart review. Data from all consecutive patients with node-positive epithelial ovarian cancer (stages IIIC and IV) who underwent cytoreductive surgery at the Mayo Clinic from 1996 to 2000 were reassessed to evaluate the prognostic significance of the new FIGO stages. Multivariate Cox regression was performed, and Kaplan-Meier survival curves constructed. RESULTS: The distribution of the restaged patients was as follows: IIIA1, 23 patients (IIIA1i, 9 patients; and IIIA1ii, 14 patients); IIIA2, 3 patients; IIIB, 4; IIIC, 67 patients; IVA, 4 patients; and IVB, 15 patients. In the univariate analysis, the relative risk for positive nodes greater than 10 mm on the longer axis was 2.57 and 3.00 for patients with microscopic peritoneal disease, compared with patients with microscopic positive nodes. However, the difference was not statistically significant. Moreover, the univariate analyses revealed statistically significant differences for 2014 FIGO stages (IIIA, IIIB, IIIC, and IVA-B), anatomical sites of peritoneal metastases, and disease staged at IIIC because of the presence of omental metastases. Multivariate analysis showed that survival was higher in patients restaged to IIIA-B than in those restaged to IIIC and IV (hazard ratios, 2.75 and 3.16, respectively; P = 0.002). The hazard ratio for patients with abdominal peritoneal metastases was 2.76 compared with patients with pelvic peritoneal metastases (P = 0.001). CONCLUSIONS: The current 2014 FIGO staging system for ovarian cancer successfully correlates survival, anatomical location of peritoneal metastases, and extra-abdominal lymph node metastases.

The impact of pelvic retroperitoneal invasion and distant nodal metastases in epithelial ovarian cancer.

BACKGROUND: The absence of disease after debulking surgery is the most important prognostic factor in the treatment of advanced epithelial ovarian cancer (EOC). Occasionally, the presence of extra-abdominal disease complicates the ability to obtain a complete surgery, considering some locations of the metastatic disease as unresectable. The objective of the study was to estimate the survival impact of pelvic retroperitoneal invasion and extrapelvic and aortic distant nodal metastases in EOC patients. The anatomical landmarks of primary cytoreductive surgery will be discussed. MATERIAL AND METHODS: We reviewed data from 116 consecutive Mayo Clinic patients with epithelial ovarian cancer (EOC) stage IIIC and IV, undergoing primary cytoreduction surgery between 1996 and 2000. Univariate and multivariate analysis for patients with positive distant nodes and pelvic retroperitoneal invasion was performed, including 57 patients with no residual disease after surgery. Kaplan-Meier curves were used to estimate the probability of survival. RESULTS: The median patient's age was 65 years (range 24-87 years). The 5 years overall survival was 44.8% (range 30.1-57.9 months) and the median length of survival was 39.9 months (range 0.13-60 months, 95% confidence interval: 30.1-57.9). Pelvic retroperitoneal invasion was present in 22 EOC patients (18.9%) and distant positive nodes were noted in 11 (9.5%): suprarenal/celiac (5.2%), inguinal (4.3%) and supraclavicular (0.9%). Univariate and multivariate Cox regression analysis, identified distant positive lymph nodes and pelvic retroperitoneal invasion as factors statistically associated with overall survival (p = 0.002 and p = 0.025, respectively). CONCLUSIONS: Metastatic distant nodes and pelvic retroperitoneal invasion are independent prognostic factors for survival in patients with advanced EOC.