Surgical aspects in therapy of primary ovarian cancer

Einleitung: Die qualitative primäre zytoreduktive Chirurgie (CRS) mit dem Ziel, eine makroskopische Tumorfreiheit zu erreichen, ist die wichtigste Voraussetzung, um prognostisch günstige Langzeitergebnisse bei Patientinnen mit primärem Ovarialkarzinom zu erzielen. Zunächst wurde die Prognose von Patientinnen nach inkompletter primärer CRS, sogenannte Komplettierungsoperation, sowie inadäquatem Staging untersucht. Weiterhin wurden die prognostische Bedeutung von Peritonealkarzinose (PC) und Lymphknotenbefall in FIGO Stadium III sowie Voraussagemöglichkeiten für Tumorresektabilität in fortgeschrittenen Stadien evaluiert. Methodik: Patientenbezogene Daten, Gewebe- und Blutproben wurden im Rahmen des Tumorbank Ovarian Cancer (TOC) Projektes gesammelt. Die Überlebenszeiten für die Studien wurden anhand der Kaplan-Meier Methode und der CoxRegressionsanalyse berechnet. Für die Auswertung der Peritonealkarzinose wurde der von Sugarbaker et al. entwickelte PCI-Score und der seit 2003 in unserer Institution eingeführte systematische IMO-Score (Intraoperative Mapping of Ovarian cancer) angewandt. Ergebnisse: Von insgesamt 111 Patienten in fortgeschrittenen FIGO Stadien konnten 74 (66,6%) trotz extern durchgeführter inkompletter CRS makroskopisch tumorfrei operiert werden. Die Gesamtüberlebenszeit von Patienten ohne Resttumor betrug 70 Monate (95% CI, 61,3-81,5) beziehungsweise 24,7 Monate mit Resttumor (95% CI, 7,1- 42,4; p<0.0001). Nach der Komplettierungsoperation konnten 47 (28,6%) und 12 (6,7%) Patientinnen in FIGO Stadium IIIC und IV eingestuft werden. In der Subgruppe der Patientinnen mit Lymphknotenbefall (LK-Befall) in FIGO Stadium III war die Gesamtüberlebensrate (OS) signifikant besser im Vergleich zur Subgruppe mit PC oder mit PC und gleichzeitigem LK-Befall (p<0.01). Das mediane progressionsfreie Überleben (PFS) war in der Subgruppe mit paraaortalen Lymphknoten (LK) Metastasen signifikant länger als beim Befall von pelvinen LK (28 und 18 Monate; p=0.02). In den ersten 3 Jahren hatten 90% der Patientinnen im FIGO IIIA1(i) Stadium und 62,6% im FIGO IIIA1(ii) Stadium kein Rezidiv (HR 2.30, 95% CI 0.45–11.58). Mithilfe der ROC-Kurve stellten wir die Grenzwerte von CA 125, PCI- und IMO-Score und prädikative Bedeutung dieser Faktoren für die Tumorresektabilität fest. 2 Schussfolgerung: Die Komplettierungsoperation zeigte, dass eine makroskopische Tumorfreiheit selbst bei primär inkomplett operierten Patienten nach der angemessenen, stadiengerechten Chirurgie erreichbar ist. Weiterhin hatten die Patientinnen mit alleinigem LK-Befall ohne PC im FIGO IIIC-Stadium eine signifikant bessere Prognose. Zudem war der Befall von paraaortalen LK prognostisch günstiger. Betrachtet man die Prognose von Patientinnen innerhalb von Stadium IIIA, so zeigt sich, dass die Patientinnen mit LK Metastasen <10 mm zu einem besseren klinischen Resultat tendieren. Ferner konnten wir nachweisen, dass präoperative CA 125 Werte >600 U/mL, PCI-Score >20 und IMO-Score >6 eine Tumorresektabilität in fortgeschrittenen FIGO Stadien vorhersagen.Introduction: Optimal and qualitative CRS, following previous appropriate staging, is the main and most powerful requirement to achieve the best outcome in patients with primary ovarian cancer. First, we evaluated the outcome of patients who underwent incomplete primary CRS so-called completion surgery. Furthermore, we analyzed the predictive value of peritoneal carcinomatosis and lymph node involvement pattern in FIGO Stadium III, as well as instruments to predict tumor resectability in advanced disease. Methods: All clinical-pathological data, tissue and blood samples were collected as part of the project „Tumor Bank Ovarian Cancer“ (TOC). Survival analyses were performed using Kaplan-Meier curves and Cox proportional hazards models. For the evaluation of peritoneal carcinomatosis the PCI-Score by Sugarbaker and IMO-Score (Intraoperative Mapping of Ovarian cancer) was used, which was developed in 2003 in our institution as a systematic surgical documentation tool. Results: Out of 111 advanced EOC patients, 74 (66.6%) could be operated macroscopically tumor free. Mean overall survival for patients without versus those with any tumor residual was 70 months (95% CI, 61.3-81.5) versus 24.7 months (95% CI, 7.1-42.4; P < 0.0001). After applying completion surgery, 47 (28.6%) and 12 (6.7%) patients were upstaged in FIGO IIIC and IV stages, respectively. The median OS differed significantly between patients with para-aortic lymph node involvement only 3 versus patients with both pelvic and para-aortic involvement (68.5 vs. 46.7 months; p = 0.02). Three-year PFS was 90 % in FIGO IIIA1(i) and 62.6 % in FIGO IIIA1(ii) (HR 2.30, 95 % CI 0.45–11.58). Using a receiver operating characteristic analysis, cut-off values for CA125, PCI and IMO scores could be defined for tumor resectability. Conclusion: Completion surgery maintained that after applying appropriate surgery techniques macroscopically, a disease-free situation is achievable and outcomes are comparable with the results of primary debulking surgery. The patients with FIGO stage IIIC with lymph node involvement only had the best clinical outcome compared with patients in the same stage with peritoneal involvement only. Involvement of only paraaortic lymph nodes in this stage resulted in a better chance of survival. Considering the prognosis in FIGO Stadium IIIA, the patients with lymph node metastasis < 10 mm tend to have better clinical outcome. Furthermore, we found that pre-operative CA125 >600 U/mL, PCI-Score >20, and IMOScore >6 could be used as predictors of complete tumor resection

Can a morphological description of the peritoneal carcinomatosis in advanced ovarian cancer add prognostic information? Analysis of 1686 patients of the tumor bank ovarian cancer

BackgroundPeritoneal carcinomatosis in ovarian cancer is frequent and generally associated with higher stage and poorer outcome. The clinical features of peritoneal carcinomatosis are diverse and their relevance for surgical and long-term outcome remains unclear. We conducted this prospective study to describe intraoperatively the different features of peritoneal carcinomatosis(PC) and correlate them with clinicopathological features, progression-free(PFS) and overall survival (OS),.MethodsWe performed a systematic analysis of all patients with documented intraoperative PC and a primary diagnosis of epithelial ovarian, tubal, or peritoneal cancer from January 2001 to September 2018. All data were evaluated by using the systematic tumor bank tool. Specific PC features included texture(soft-hard), consistency(coarse-fine or both), wet vs dry(PC with ascites vs. PC without ascites), and localization(diffuse-local). PC characteristics were then evaluated for correlation with age, FIGO-stage, histology, lymph-node involvement, grade, and presence of residual tumor at primary surgery. Moreover, the influence of PC characteristics on OS and PFS was analyzed.ResultsA total of 1686 patients with PC and primary epithelial ovarian cancer were included. Majority of the patients were characterized by diffuse PC(73.9%). The majority of peritoneal nodules were fine in texture (55.3%) and hard in consistency (87.4%). Moreover, 27.6% of patients had dry PC. Diffuse PC localization was significantly associated with higher FIGO-stage (pConclusionDiffuse localization of peritoneal carcinomatosis was significant predictor of recurrence. Lower OS and PFS were associated with diffuse peritoneal localization, wet PC, and additional lymph node involvement. Further prospective trials are warranted with the inclusion of translational research aspects to better understand the different peritoneal carcinomatosis patterns