Postoperative leukopenia after cytoreductive surgery and hypertherm intraperitoneal chemotherapy for colorectal carcinomatosis- causes and implication on outcomes in a population-based study.

BACKGROUND

Leukocytes have been reported to have tumor stimulating effects in colorectal cancer, among other malignancies. In line with this, earlier research has shown improved disease-free survival in patients with postoperative neutropenia compared to non-neutropenic patients following cytoreductive surgery (CRS) and hypertherm intraperitoneal chemotherapy (HIPEC).

AIM: To evaluate the impact of postoperative leukopenia after CRS and HIPEC on recurrence rate, survival, and risk of complications.

METHODS

All CRS and HIPEC-procedures for colorectal adenocarcinoma in the national Swedish HIPEC-registry since 2015 and local registries in Uppsala and Malmö since 2003 until December 31st, 2021, were included (n = 921). Patients who did not complete a full CRS and HIPEC procedure (n = 99), had incomplete macroscopic cytoreduction (n = 25) or a lack of information on leukocyte count (n = 213) were excluded, resulting in 584 analyzed cases. Primary outcome was overall recurrence rate. Secondary outcomes were overall survival, recurrence-free survival, and perioperative complications.

RESULTS

Postoperative leukopenia was observed in 54 (9.2%) cases of which 32 (5.5%) developed severe leukopenia. No differences in patient characteristics were noted between those with or without leukopenia. There were no differences in 3-year recurrence rate, overall survival or 3-year recurrence-free survival, between the groups. Neoadjuvant chemotherapy treatment, HR 1.32 (95% CI: 1.02-1.71), higher PCI-score, HR 1.50 (95% CI: 1.09-2.05) and higher pN-stage HR 2.52 (95% CI: 1.74-3.65) were associated with higher 3-year recurrence rate. 3-year mortality was associated with neoadjuvant chemotherapy treatment, HR 1.82 (95% CI: 1.06-3.11), severe postoperative complication, HR 2.39 (95% CI: 1.39-4.13) and high PCI-score, HR 2.60 (95% CI: 1.31-5.14). Treatment with combined oxaliplatin/irinotecan, HR 12.34 (95% CI: 4.51-33.74) was associated with developing postoperative leukopenia. Longer operation time, HR 2.30 (95% CI: 1.55-3.42), and severe leukopenia, HR 3.50 (95% CI: 1.25-9.77) were associated with postoperative complication.

CONCLUSIONS

Postoperative leukopenia did not impact recurrence rate or long-term survival in a statistically significant manner. Neoadjuvant chemotherapy and high PCI-score were associated with both recurrent disease and mortality within 3 years.