Increased Survival of Patients with Synchronous Colorectal Peritoneal Metastases Receiving Preoperative Chemotherapy Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) can result in long-term survival for selected patients with colorectal peritoneal metastases (PM). Most patients are additionally treated with systemic chemotherapy, but timing (adjuvant vs. preoperative) varies between treatment centers. This study aimed to compare short- and long-term outcomes for patients with synchronous colorectal PM undergoing CRS + HIPEC who received preoperative or adjuvant chemotherapy. METHODS: This study enrolled patients with synchronous colorectal PM who underwent macroscopically complete or near complete CRS + HIPEC. Data were collected from a prospective database containing all patients between 2007 and 2014. Perioperative outcome and survival were compared between patients who underwent adjuvant chemotherapy (adjuvant strategy [AS]) and those who had preoperative chemotherapy followed by adjuvant systemic chemotherapy if possible (preoperative strategy [PS]). RESULTS: The study enrolled 91 patients, 25 (28 %) of whom received preoperative chemotherapy. The peritoneal cancer index (PCI) score was lower and the operation length shorter for the patients receiving preoperative chemotherapy (both p = 0.02). The complication rates were comparable between the two groups. The median survival after diagnosis was 38.6 months in the AS group, whereas median survival was not reached in the PS group (p < 0.01). The 3-year overall survival rates were 50 and 89 %, respectively. After correction for other significant prognostic factors, preoperative chemotherapy was independently associated with improved survival (HR 0.23; 95 % confidence interval, 0.07-0.75; p = 0.01). CONCLUSION: Treatment with preoperative chemotherapy was associated with improved long-term survival after CRS + HIPEC compared with adjuvant chemotherapy. Ideally, a randomized controlled trial should be performed to investigate the optimal timing of systemic chemotherapy for colorectal PM patients.

Incidence and treatment of recurrent disease after cytoreductive surgery and intraperitoneal chemotherapy for peritoneally metastasized colorectal cancer: A systematic review.

INTRODUCTION: The optimal treatment for peritoneal carcinomatosis (PC) of colorectal origin is a combination of cytoreductive surgery and intraperitoneal chemotherapy (CRS + IPC). Although 5-year survival rates of up to 40% have been reported, recurrent disease remains common and is estimated to be a strong negative prognostic factor for survival. This systematic review elaborates on the incidence of recurrent disease and the possibilities to prevent and treat recurrence. METHODS: Two searches were performed. To identify the magnitude of recurrent the disease, a search was performed in Pubmed and EMBASE until September 2014. A second search was performed in Pubmed to identify treatment of recurrent disease with secondary CRS + IPC. RESULTS: The first search resulted in 139 and 94 articles in Pubmed and EMBASE respectively. Among those, 28 were included. Overall recurrence rates ranged from 22.5 to 82%. Local, systemic and combined local-systemic recurrence ranged from 6 to 42.5%, 10.4-43% and 5.8-21.5%. Median time to recurrence varied from 9 to 23 months, three-year disease free survival ranged from 14 to 41.5%. The second search resulted in 140 articles among which 17 met the inclusion criteria. A total of 190 patients underwent secondary CRS. Median survival after the second procedure ranged from 18 to 55.7 months. One, two and three-year survival ranged between 66 and 94, 44-50 and 0-66%. CONCLUSION: Recurrence is very common after cytoreductive surgery and intraperitoneal chemotherapy for PC of colorectal origin. Repeat cytoreductive surgery suggests a potential survival benefit for a highly selected group. Therefore, strategies to prevent recurrence are of the utmost importance.

Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology.

BACKGROUND: Signet ring cell cancer (SRCC) patients have a poor oncologic outcome. The aim of this study was to determine whether the potential drawbacks of hyperthermic intraperitoneal chemotherapy (HIPEC) outweigh the benefits in patients with peritoneally metastasized SRCC. METHODS: Patients with peritoneal carcinomatosis (PC) of colorectal origin referred to two tertiary centers between April 2005 and December 2013 were identified and retrospectively analyzed. Data were compared between SRCC histology and other differentiations. RESULTS: Three-hundred-fifty-one patients were referred for CRS+HIPEC among which 20 (5.7%) patients were identified with SRCC histology. CRS + HIPEC was performed in 16 of these 20 (80%) and 252 out of the 331 remaining patients (76.1%). A higher proportion of patients in the SRCC-group were diagnosed with N2 stage (62.5% vs. 36.1%, P=0.04). A macroscopic complete resection was achieved in 87.5% and 97.2% respectively (P=0.04). Median survival was 14.1 months compared to 35.1 months (P<0.01). Recurrence occurred in 68.8% of the SRCC patients and in 43.7% of the other histology patients (P=0.05). CONCLUSION: Patients with SRCC and PC treated with CRS+HIPEC have a poor median survival only slightly reaching over 1 year. In the presence of other relative contraindications, SRCC histology should refrain a surgeon from performing CRS and HIPEC.

Peritoneal cancer patients not suitable for cytoreductive surgery and HIPEC during explorative surgery: risk factors, treatment options, and prognosis.

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the only curative option for patients with peritoneal carcinomatosis of colorectal origin. Despite meticulous preoperative assessment, CRS and HIPEC appear to be impossible in a subset of patients at the time of surgery. This study investigated which clinical factors may identify these patients before surgery and reported on factors influencing survival. METHODS: All patients with PC of colorectal origin between April 2005 and November 2013 who underwent exploratory surgery to determine whether cytoreduction and HIPEC was feasible were included in this study. Details concerning preoperative patient characteristics, perioperative outcomes, treatment and survival were compared. RESULTS: In total, 350 patients with PC were referred to evaluate the possibility of CRS + HIPEC of which 268 (76.6 %) underwent CRS and HIPEC and 82 (23.4 %) had an open-close procedure. The main reason for discontinuing surgery was widespread peritoneal disease (50 %). A preoperative ostomy and an ASA score of 3 were associated with an increased risk for "open and close" (O&C). Median survival was 11.2 months in patients treated with palliative chemotherapy (75 %) compared with 2.7 months with palliative care only. CONCLUSIONS: CRS and HIPEC were deemed unsuitable in almost a quarter of all patients undergoing surgery. No strong clinical predictors for O&C were found, stressing the need for better preoperative imaging modalities. Survival in these patients is limited, but the majority could be treated with palliative chemotherapy resulting in survival of almost 1 year.