Impact of Previous Gynecologic Surgical Procedures on Outcomes of Non-Gynecologic Peritoneal Malignancies Mimicking Ovarian Cancer: Less Is More?

BACKGROUND: Non-gynecologic rare peritoneal surface malignancies (PSMs) often are misdiagnosed as disseminated ovarian cancer and initially treated by gynecologic surgeons. This study aimed to assess whether these previous maneuvers (i.e., full surgical staging and/or cytoreductive attempts) affect outcomes after the definitive surgery performed in a tertiary center. METHODS: The study reviewed 298 women affected by non-gynecologic PSM who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after previous gynecologic surgery. Prior surgery was categorized as limited surgery (pLS: abdominal exploration with biopsy plus adnexectomy and/or appendectomy) or extended surgery (pES: full surgical staging or cytoreductive attempts including hysterectomy with bilateral salpingo-oophorectomy). RESULTS: Of the 298 patients, 143 had pLS and 153 had pES. Morbidity was similar between the groups (P = 0.143), but the pES group had more severe urinary tract injuries (19 vs. 3; P < 0.001), longer operating time (585.9 vs. 506.7; P = 0.027), and more patients needing more than two anastomoses (41 vs. 26; P = 0.033). Age older than 55 years (odds ratio [OR] 2.42; P = 0.009) and number of anastomoses (OR 3.17; P = 0.002) correlated with severe morbidity; pES correlated with urinary tract grades 3 and 4 injuries (OR 7.9; P = 0.001). The 5-year cumulative incidence of locoregional relapse was significantly higher in the pES group (0.41 vs. 0.27; P = 0.012; median follow-up period, 69 months). The multivariate analysis identified a Peritoneal Carcinomatosis Index (PCI) higher than 20 and pES as independent risk factors. CONCLUSION: For women undergoing CRS±HIPEC for non-gynecologic PSM, the risk for locoregional relapse and severe postsurgical urinary tract complications is increased by pES. Therefore, prior full surgical staging or cytoreductive attempts without definitive gynecologic histology should be avoided. Prophylactic ureteral stenting and stricter oncologic follow-up assessment must be considered in this scenario.

Comparative study of mucinous and non-mucinous appendiceal neoplasms with peritoneal dissemination treated by cyoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Appendiceal non-mucinous neoplasms (AnMN) are rare and poorly understood malignancies with no standard treatment. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is largely used to treat peritoneal disseminations from appendiceal mucinous neoplasms (AMN), but its role with AnMN is unclear. METHODS: A prospective database of 315 patients with advanced appendiceal primaries undergoing CRS/HIPEC during 1996-2020 was reviewed. Baseline characteristics, operative and long-term outcomes of AnMN were compared with those of AMN. AMN were categorized according to PSOGI classification into high-grade, low-grade, and acellular mucin (AC), based on peritoneal disease histology. RESULTS: Twenty-three patients (7.3%) with goblet cell carcinoma (GCC; n = 9), intestinal-type adenocarcinoma (ITAC; n = 12), and mixed adeno-neuroendocrine carcinoma (MANEC; n = 2) were identified. AnMN patients were more likely to be males (P = 0.006), have preoperative systemic chemotherapy (P = 0.001), grossly incomplete CRS (P = 0.001), and nodal metastases (P = 0.001), but not systemic relapse after CRS/HIPEC (P = 0.133). Median follow-up was 25.1 months (range 0.8-77.3) for AnMN, and 80.9 months (range 0.1-279.2) for AMN. Median overall survival was 24.0 months for AnMN, 66.2 months for high-grade AMN (P = 0.015), 160.0 months for low-grade ANM (P = 0.001), and not reached for AC (P = 0.001). Among AnMN patients, median survival was 23.4 months for GCC, 38.7 months for ITAC, 20.3 months for MANEC (P = 0.855). In the overall series, histological subtype (P = 0.001), incomplete cytoreduction (P = 0.001), and positive lymph-nodes (P = 0.003) correlated with poorer survival at multivariate analysis. CONCLUSIONS: AnMN share with AMN a predominant local-regional dissemination pattern, but prognosis after CRS/HIPEC is worse. This strategy needs to be carefully considered for AnMN.

Prognostic Impact of Primary Side and RAS/RAF Mutations in a Surgical Series of Colorectal Cancer with Peritoneal Metastases.

BACKGROUND: Selecting patients with colorectal cancer peritoneal metastases (CRC-PMs) for surgery is still a concern. Biological features have the potential to improve prognostic stratification, but their significance in this clinical setting is still unclear. We assessed the prognostic impact of primary side and KRAS/NRAS/BRAF/PIK3CA mutations in patients treated with either cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) or CRS alone. METHODS: We reviewed a prospective database of 152 CRC-PM patients selected to undergo perioperative systemic chemotherapy and CRS with or without HIPEC. Extensive mutational analysis of KRAS, NRAS, BRAF, and PIK3CA was performed by polymerase chain reaction (PCR). In 68 patients, Ion Torrent next-generation sequencing technology was used to characterize the hotspot regions of 50 genes. RESULTS: The primary tumor was right-sided in 61 patients (40.1%) and left-sided in 91 patients (59.9%). Right-sided primaries were associated with mutated KRAS (p = 0.01) and normal carcinoembryonic antigen (CEA; p = 0.03). KRAS was mutated in 71/152 patients (46.7%), NRAS in 7/152 patients (4.6%), BRAF in 10/152 patients (6.6%), PIK3CA in 17/78 patients (25.0%), TP53 in 37/68 patients (54.4%), APC in 25/68 patients (36.7%), SMAD4 in 13/68 patients (19.1%), and FBXW7 in 5/68 patients (7.4%). Median follow-up was 54.9 months and median survival from PM diagnosis was 45.1 months. The right-sided primary (hazard ratio [HR] 1.62, 95% confidence interval [CI] 0.43-0.89; p = 0.011), BRAF mutations (HR 2.21, 95% CI 1.05-4.63; p = 0.038), and Peritoneal Cancer Index (HR 1.47, 95% CI 1.03-2.10; p = 0.036) independently correlated with poorer survival, while APC mutations univariately correlated with better survival (p = 0.03). CONCLUSIONS: BRAF mutations and right-sided primary are adverse prognostic factors that may be used to optimize therapeutic strategies. APC may be involved in CRC-PM development and progression.