Peritoneal metastases from rare ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Objectives: There are limited treatment options and no consensus on the management of advanced rare ovarian malignancies. Rare ovarian malignancies can present with peritoneal metastases (PM), featuring a similar presentation to more common ovarian subtypes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for PM of non-gynecologic origin and, recently, epithelial ovarian cancer. We evaluated the feasibility of CRS/HIPEC in the management of PM from rare ovarian malignancies and report postoperative outcomes on these patients. Methods: A retrospective review of a single center, prospective database (1994-2021) was performed to identify patients with rare ovarian malignancies treated with CRS/HIPEC. Clavien-Dindo 90-day morbidity/mortality and Kaplan-Meier overall (OS) and progression-free survival (PFS) were analyzed. Results: Of 44 patients identified, 28 underwent CRS/HIPEC. Six were aborted due to extensive disease. Histologic subtypes included: clear cell (5/28, 17.9 %), endometrioid (5/28, 17.9 %), granulosa cell (3/28, 10.7 %), low-grade serous (6/28, 21.4 %), mesonephric (1/28, 3.6 %), mucinous (6/28, 21.4 %), and small cell (2/28, 7.1 %) carcinomas. Eight (28.6 %) patients had primary and 20 (71.4 %) had recurrent disease. Median peritoneal cancer index (PCI) was 21 (IQR: 6-29). Complete cytoreduction (<2.5 mm residual disease) was achieved in 27/28 (96.4 %). Grade III/IV complications occurred in 9/28 (32.1 %) with one (3.6 %) mortality. After a median follow-up of 65.8 months, 20 patients were alive. Five-year OS and PFS were 68.5 and 52.6 %, respectively. Conclusions: In patients with PM from rare ovarian malignancies, CRS/HIPEC is feasible and has an acceptable safety profile. Longer follow-up and multicenter trials are needed.

Collaborative expertise of gynecological and surgical oncologists in managing advanced epithelial ovarian cancer.

BACKGROUND: Most patients with epithelial ovarian cancer (EOC) present with significant peritoneal spread. We assessed collaborative efforts of surgical and gynecological oncologists with expertise in cytoreductive surgery (CRS) in the management of advanced EOC. METHODS: Using a prospective single-center database (2014-2022), we described the operative and oncologic outcomes of stage IIIC-IVA primary and recurrent EOC perioperatively managed jointly by gynecological and surgical oncologists both specializing in CRS and presented components of this collaboration. RESULTS: Of 199 identified patients, 132 (66 %) had primary and 53 (27 %) had recurrent EOC. Due to inoperable disease, 14 (7 %) cases were aborted and excluded from analysis. Median peritoneal cancer index (PCI) in primary and recurrent patients was 21 (IQR: 11-28) and 21 (IQR: 6-31). Upper abdominal surgery was required in 95 % (n = 125) of primary and 89 % (n = 47) of recurrent patients. Bowel resections were performed in 83 % (n = 110) and 72 % (n = 38), respectively. Complete cytoreduction (CC-0/1) with no disease or residual lesions <2.5 mm was achieved in 95 % (n = 125) of primary and 91 % (n = 48) of recurrent patients. Ninety-day Clavien-Dindo grade III-IV morbidity was 12 % (n = 16) and 21 % (n = 11), respectively. Median follow-up was 44 (95%CI: 33-55) months. Median overall survival in primary and recurrent EOC was 68 (95%CI: 45-91) and 50 (95%CI: 16-84) months. Median progression-free survival was 26 (95%CI: 22-30) and 14 (95%CI: 7-21) months, respectively. CONCLUSIONS: Perioperative collaboration between surgical and gynecological oncologists specializing in CRS allows safe performance of complete cytoreduction in the majority of patients with primary and recurrent EOC, despite high tumor burden.

Sufficient Regional Lymph Node Examination for Staging Adenocarcinoma of the Appendix.

BACKGROUND: The presence of lymph node (LN) metastasis is a known negative prognostic factor in appendix cancer (AC) patients. However, currently the minimum number of LNs required to adequately determine LN negativity is extrapolated from colorectal studies and data specific to AC is lacking. We aimed to define the lowest number of LNs required to adequately stage AC and assess its impact on oncologic outcomes. METHODS: Patients with stage II-III AC from the National Cancer Database (NCDB 2004-2019) undergoing surgical resection with complete information about LN examination were included. Multivariable logistic regression assessed the odds of LN positive (LNP) disease for different numbers of LNs examined. Multivariable Cox regressions were performed by LN status subgroups, adjusted by prognostic factors, including grade, histologic subtype, surgical approach, and documented adjuvant systemic chemotherapy. RESULTS: Overall, 3,602 patients were included, from which 1,026 (28.5%) were LNP. Harvesting ten LNs was the minimum number required without decreased odds of LNP compared with the reference category (≥ 20 LNs). Total LNs examined were < 10 in 466 (12.9%) patients. Median follow-up from diagnosis was 75.4 months. Failing to evaluate at least ten LNs was an independent negative prognostic factor for overall survival (adjusted hazard ratio 1.39, p < 0.01). CONCLUSIONS: In appendix adenocarcinoma, examining a minimum of ten LNs was necessary to minimize the risk of missing LNP disease and was associated with improved overall survival rates. To mitigate the risk of misclassification, an adequate number of regional LNs must be assessed to determine LN status.

Patterns of Recurrence in Appendix Cancer After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: It is thought that low-grade (LG) appendiceal cancer (AC) demonstrates predominantly intraperitoneal recurrence (IPR) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), whereas high-grade (HG) tumors progress both intra- and extraperitoneally (EPR). However, evidence supporting this conception is lacking; therefore, we assessed recurrence in various AC histologies. METHODS: A retrospective, cohort study was conducted by using a single-center database (1998-2022). Recurrence patterns (IPR, EPR, combined) were identified for LG, HG, high-grade with signet ring cells (SRC), and goblet cell carcinoma (GCC). RESULTS: We included 432 complete (CC-0/1) CRS/HIPECs: 200 LG, 114 HG, 72 SRC, and 46 GCC. Median follow-up was 78 (95% confidence interval [CI] 70-86) months. Overall, 34% (n = 148) of patients recurred. IPR was the most common (LG 16%, HG 27%, SRC 36%, GCC 26%) with median time to recurrence (MTR) of 21 (IQR: 12-40) months. EPR (liver, lung, pleura, lymph nodes, or bones) occurred in LG 3%, HG 9%, SRC 22%, and GCC 7%. MTR was 11 (IQR: 4-16) months. Combined pattern occurred in LG 0%, HG 8%, SRC 7%, and GCC 0%. MTR was 13 (IQR: 7-18) months. Iterative surgery was performed in 53% IPR, 18% EPR, and 51% combined. Median post-recurrence survival was longer after IPR compared with EPR and combined recurrence: 36 (95% CI 25-47) versus 13 (95% CI 7-19) and 18 (95% CI 6-30) months (p < 0.01). CONCLUSIONS: After complete CRS/HIPEC, IPR was the predominant pattern in all AC histologies and occurred later. Post-recurrence survival after IPR was longer. Knowing AC recurrence patterns can help to understand its biology and plan follow-up and post-relapse management.

Achieving Intraperitoneal Disease Control Using Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Two Cases of Metastatic Breast Cancer.

Peritoneal metastases from breast cancer (PMBC) tend to occur late in the disease course and are challenging to manage. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) provide peritoneal disease control in other malignancies and may achieve similar results in PMBC. We assessed intraperitoneal disease control and outcomes in two PMBC patients after CRS/HIPEC. Patient 1, diagnosed at age 64, had hormone-positive/human epidermal growth factor receptor 2 (HER2)-negative lobular carcinoma treated with mastectomy. Prior to salvage CRS/HIPEC at age 72, five cycles of intraperitoneal chemotherapy via an indwelling catheter failed to control recurrent peritoneal disease. Patient 2, diagnosed at age 52, had hormone-positive/HER2-negative ductal-lobular carcinoma and received lumpectomy, hormonal therapy, and target therapy. Prior to salvage CRS/HIPEC at age 59, she had recurring ascites that was resistant to hormonal therapy and required multiple paracenteses. Both underwent complete CRS/HIPEC with melphalan. The only major complication was anemia, which required a transfusion in both patients. They were discharged on postoperative days 8 and 13, respectively. Patient 1 had peritoneal recurrence 26 months post-CRS/HIPEC and died of disease at 49 months. Patient 2 never had peritoneal recurrence and died of extraperitoneal progression at 38 months. In conclusion, CRS/HIPEC is safe and can provide intraperitoneal disease and symptom control in select patients with PMBC. Thus, CRS/HIPEC can be offered to these rare patients who have failed standard treatments.

Outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal dissemination from ovarian carcinosarcoma.

BACKGROUND: Ovarian carcinosarcoma (OCS) is an uncommon and aggressive malignancy, with poor response to current treatment approaches and no clear guidelines. Our aim is to evaluate the outcomes of an OCS cohort after cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A descriptive cohort study was performed. Patients who underwent CRS/HIPEC for peritoneal dissemination from tubo-ovarian malignancies (1999-2021) were retrospectively reviewed. Patients with confirmed histopathologic diagnosis of FIGO stage III/IV OCS were included. Overall (OS) and progression-free survival (PFS) were determined with the Kaplan-Meier method. RESULTS: Of 267 patients with tubo-ovarian malignancies reviewed, 7.5% (20/267) had OCS. Of these, 16 underwent CRS/HIPEC, including 9 for a new diagnosis and 7 for disease recurrence. Median age at surgery was 66.5 (IQR: 54.5-74.5) years. Nine (56.2%) patients were FIGO stage IV. Median peritoneal cancer index was 22 (IQR: 14-28). Complete cytoreduction was achieved in 15/16 (93.7%) cases. HIPEC agents included carboplatin (n = 7), cisplatin+doxorubicin (n = 4), and melphalan (n = 5). Major complications occurred in 4/16 (25%), with no 90-day mortality. Median follow-up was 41.8 months. Median PFS was 11.7 (95%CI: 10.5-17.1) months. Malignant bowel obstruction occurred in 3/16 (18.7%). Median OS from CRS/HIPEC was 21.3 (95%CI: 16.3-31.6) months, not reached for newly diagnosed vs 19.7 months for recurrent patients (p = 0.23). CONCLUSIONS: CRS/HIPEC showed promising survival and abdominal disease control with low rates of malignant obstruction in patients with advanced stage OCS. Collaborative studies with larger cohorts and longer follow-up may further elucidate the role of CRS/HIPEC in OCS.

Peritoneal metastasis of advanced epithelial ovarian carcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective international multicentric data analysis.

INTRODUCTION: The purpose of our study was to evaluate outcome data after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis originating from advanced epithelial ovarian carcinoma (PMOC). PATIENTS AND METHODS: A retrospective international multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group. RESULTS: One thousand four hundred and ninety-one patients from 11 specialized units underwent CRS and HIPEC that of those 326 (21.9%) upfront surgeries, 504 (33.8%) interval surgery, and 661(44.3%) recurrent cases. Complete Cytoreduction(CC0/1) was achieved in 1213 patients (81.3%). Treatment -related mortality was 0.8%, major operative complications (Grades 3-5) was 25.1%. Factors associated with major operative complications include prior surgical score (PSS for recurrent cases; RC) PSS>2,p = 0.000), PCI(≤15, >15 cut-off level; p ≤ 0.000), completeness of cytoreduction (CC, p=0.000), high CA125 levels (>25 mg/dl), presence of ascites, high CRP (>5 mg/dl) levels and low albumin levels (below to 2.5 mg/dl) (p ≤ 0.05). The median survival was 58 months in upfront surgery(UFS), 60 months in interval surgery(IS), and 42 months in RC. The overall survival for five years was 45% for UFS, 37% for IS, 28% for RC cases. CCscore (p = 0.000), CA125, CRP and albumin levels (p ≤ 0.05) were predictors for progression free survival. PCI(p ≤ 0.000), major postoperative complications (p = 0.004), incomplete CRS(CC2/3)(p < 0.001), prior chemotherapy (hazard ratio [HR], 3-8; p < 0.001) and PSS>2 for RC were independent predictors of poor overall survival. CONCLUSION: The combined treatment strategy for PMOC may be performed safely with acceptable morbidity and mortality in the specialized units.

Adjuvant chemotherapy for high-grade appendiceal cancer after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: There are no available data on the efficacy of adjuvant chemotherapy (ACT) in stage IVA/B high-grade mucinous appendiceal cancer treated with CRS/HIPEC. We evaluated the association between ACT and survival in this cohort. MATERIALS AND METHODS: A single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade mucinous appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1 were included. Survival was compared between ACT and no chemotherapy (NoCT) patients. Subgroup analysis was performed with adjustment for confounding variables. RESULTS: We identified 180 patients: 77 ACT and 103 NoCT. ACT regimens included 5-FU/capecitabine (13%), oxaliplatin-based (63%), and irinotecan-based (21%), combined with bevacizumab in 27% of cases. Median number of cycles was 9 (IQR: 6-12). Median overall survival (OS) did not significantly differ between ACT and NoCT (53 vs 75 months, p = 0.566). Multivariable Cox regression showed no OS benefit for ACT vs NoCT in patients with neoadjuvant chemotherapy (HR 1.14; 95%CI: 0.38-3.39) or without it (HR 1.33; 95%CI: 0.69-2.57), with signet ring cell (HR 0.89; 95%CI: 0.38-2.06) or other histologies (HR 1.11; 95%CI: 0.50-2.46), positive lymph nodes (HR 1.60; 95%CI: 0.74-3.49), or peritoneal cancer index ≥20 (HR 1.08; 95%CI: 0.55-2.11) after adjusting for other factors. CONCLUSIONS: In our cohort, colon-type ACT was not associated with better OS in stage IVA/B mucinous appendiceal cancer after CRS/HIPEC, even after adjusting for confounders. This may be due to different tumor biology than colon cancer or small sample size. Prospective collaborative studies are needed.

Safety of Nephrectomy Performed During CRS/HIPEC: A Propensity Score-Matched Study.

BACKGROUND: Surgeons may hesitate to perform nephrectomy (NE) during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) due to a potential increase in morbidity. However, no data are available regarding the impact of NE on outcomes, so the authors decided to assess its safety during CRS/HIPEC. METHODS: A single-center propensity score-matched study was conducted using a prospective database (1994-2021). The study included patients who underwent NE during CRS/HIPEC with completeness of cytoreduction (CC) of 0, 1, or 2. Control subjects (no-NE) were selected in a 1:3 ratio using propensity score-matching weighted by age, histology, peritoneal cancer index (PCI), CC-0 or CC-1 rate, and length of surgery. RESULTS: Among 828 patients, 13 NE and 39 no-NE control subjects were identified. The indications for NE included tumor involvement of the ureter, hilum, and/or kidney with preserved (n = 8), decreased (n = 2), or absent (n = 3) function. NE patients received more intraoperative intravenous (IV) fluids (16,000 vs 11,500 mL; p = 0.045) and had a greater urine output (3200 vs 1913 mL; p = 0.008). NE patients received mitomycin C (40 mg for 90 min) or melphalan (50 mg/m2 for 90 min) without reduction of dose or time. Major morbidity (p = 0.435) and mortality (p = 1.000) were comparable between the two groups. No postoperative acute kidney injury was seen in either group. Adjuvant chemotherapy was administered to 46.2% of the NE and 35.9% of the no-NE patients (p = 0.553), with similar starting times (p = 0.903) between the groups. CONCLUSIONS: Nephrectomy performed during CRS/HIPEC does not seem to increase postoperative morbidity or to delay adjuvant chemotherapy, and NE can be performed if required for complete cytoreduction. The NE patients in our cohort did not have a reduction of mitomycin C or melphalan dose or perfusion time.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

The Role of Microorganisms in Appendiceal Pseudomyxoma Peritonei: A Review.

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. It originates from neoplasms of the appendix and leads to the formation of peritoneal implants and the accumulation of mucinous ascites. PMP represents a spectrum of low to high-grade disease. Despite aggressive management, many PMP patients recur, leading to debilitating symptoms and few treatment options. Therefore, scientists have continued to look for ways to improve treatment and further understand disease pathogenesis. Microorganisms were previously hypothesized to play a role in PMP progression and development. Hence, antibacterial treatment was suggested by some authors, but the data were limited. In this paper, we review the current data on the role of bacteria in PMP, discuss the significance, and suggest possible solutions to the inherent challenges in these studies. Given the limitations of the discussed studies, we remain skeptical about introducing novel antibacterial treatment into clinical practice at this time; however, the available data are valuable and indicate that more research into the molecular mechanisms of PMP is needed.

Systemic Chemotherapy for High-Grade Mucinous Appendiceal Cancer with Peritoneal Spread After Unsuccessful CRS/HIPEC.

BACKGROUND: The best management of patients who have unresectable mucinous appendiceal cancer (MAC) with peritoneal spread after a failed attempt at cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is unclear. This study aimed to assess outcomes after systemic chemotherapy (SCT) for patients with unresectable peritoneal metastases from high-grade MAC. METHODS: A single-center retrospective cohort study was conducted using a prospective CRS/HIPEC database. The study included high-grade MAC patients with peritoneal carcinomatosis who were deemed surgical candidates, but had an aborted CRS/HIPEC or only palliative HIPEC due to unresectable disease. Overall survival (OS) was compared. RESULTS: Of 72 identified patients, 20 received SCT and 52 did not (NoCT). The groups were balanced by age (p = 0.299), sex (p = 0.930), histopathologic subtype (p = 0.096), preoperative chemotherapy (p = 0.981), and postoperative major complication rates (p = 0.338). Both groups had extensive disease (median peritoneal cancer index at exploration, 39 vs 39). The median number of cycles was 12 (interquartile range [IQR], 6-15), and the median time between the procedure and SCT was 7 weeks (IQR, 5-10 weeks). The median follow-up period was 65 months. The median OS was significantly higher for the SCT group (26 months; 95 % confidence interval [CI], 10.8-41.5 months) than for the NoCT group (12 months; 95 % CI, 9.6-14.4 months) (p < 0.001), with hazard ratio (HR) of 0.22 (95 % CI, 0.08-0.66; p = 0.007) after adjustment for other factors. CONCLUSION: Systemic chemotherapy is associated with improved OS for high-grade MAC patients with unresectable peritoneal metastases who are deemed surgical candidates but underwent an unsuccessful CRS/HIPEC attempt. Further prospective studies with a larger sample are required to identify patient subgroups who benefit the most from SCT.

Iterative Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Recurrence after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal tumors (AT) with mucinous carcinomatosis peritonei (MCP) is common. The evidence favoring iterative procedures (iCRS/HIPEC) is limited, and its benefit is not clear for all patients. METHODS: Retrospective (1998-2020) cohorts of AT patients with MCP recurrence after the first CRS/HIPEC were analyzed. Outcomes were compared within tumor grades between iCRS/HIPEC patients and matched control patients without iCRS/HIPEC using propensity score matching (1:1). Post-recurrence survival (PRS) was measured from the date of recurrence after the first CRS/HIPEC to death or last contact. RESULTS: Overall, 55 iCRS/HIPEC patients were identified: 36 low-grade (LGMCP) patients, 13 high-grade (HGMCP) patients, and 6 HGMCP patients with signet-ring features (HGMCP-S). Nine patients had a third CRS/HIPEC. The median peritoneal cancer index (PCI) scores were 33, 19 and 10, with CC-0/1 achieved for 94.4%, 78.2% and 88.9% of the patients after the first, second, and third CRS/HIPEC, respectively. No 90-day postoperative mortality occurred. The median progression-free survival from the first CRS/HIPEC was 19.7 months for the iCRS/HIPEC patients versus 14.2 months for the matched control patients (p = 0.43). The median PRS was 80.2 months for iCRS/HIPEC versus 36.2 for the control patients (p < 0.001). For the iCRS/HIPEC versus the matched control patients, the median PRS by tumor grade was 174.1 versus 51.9 (p < 0.001) for the LGMCP, 42.0 versus 12.4 (p = 0.02) for the HGMCP, and 15.4 versus 8.1 months (p = 0.61) for the HGMCP-S patients, respectively. CONCLUSIONS: Selected low- and high-grade appendiceal cancer patients with MCP recurrence able to undergo iterative CRS/HIPEC procedures showed favorable outcomes and such patients should be considered for surgery when feasible. This survival benefit with iCRS/HIPEC is not evidenced in recurrent MCP with signet ring cell morphology.