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. 2024 Mar 7;13(6):1546.
doi: 10.3390/jcm13061546.

Intraoperative Ketorolac and Outcomes after Ovarian Cancer Surgery

Mathieu Luyckx  1   2   3 , Céline Verougstraete  2 , Mathieu Jouret  4 , Kiswendsida Sawadogo  5 , Marc Waterkeyn  1   6 , Frédéric Grandjean  1   7 , Jean-Paul Van Gossum  1   8 , Nathanael Dubois  1   8 , Vincent Malvaux  1   9 , Lucie Verreth  1   9 , Pascale Grandjean  1   10 , Pascale Jadoul  2 , Charlotte Maillard  2 , Amandine Gerday  2 , Audrey Dieu  11 , Patrice Forget  12 , Jean-François Baurain  1   2   13 , Jean-Luc Squifflet  1   2
Affiliations

Intraoperative Ketorolac and Outcomes after Ovarian Cancer Surgery

Mathieu Luyckx et al. J Clin Med. .

Abstract

Introduction: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes.

Materials and methods: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020.

Results: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively.

Conclusion: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.

Keywords: NSAID; oncological surgery; ovarian cancer; peri operative inflammation.

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Conflict of interest statement

None of the authors had conflicts of interest to declare.

Figures

Figure 1
Figure 1
Comparison of the progression-free survival and overall survival between the patients receiving ketorolac during the surgery or not.
Figure 1
Figure 1
Comparison of the progression-free survival and overall survival between the patients receiving ketorolac during the surgery or not.
Figure 2
Figure 2
Progression-free survival in completely resected patients, according to the ketorolac administration or lack thereof (n = 150).
Figure 3
Figure 3
Progression-free survival in patients undergoing primary debulking surgery (without neoadjuvant chemotherapy) according to the ketorolac administration (A) and patients receiving neoadjuvant chemotherapy before surgery (B).
Figure 3
Figure 3
Progression-free survival in patients undergoing primary debulking surgery (without neoadjuvant chemotherapy) according to the ketorolac administration (A) and patients receiving neoadjuvant chemotherapy before surgery (B).
Figure 4
Figure 4
Progression-free survival of the patients younger the 69 years old according to the Ketorolac administration. (n = 109).
Figure 5
Figure 5
Progression-free survival according to the preoperative NLR and the influence of ketorolac administration during the surgery. (A) Disease-free survival in patients with NLR > 3,53 according to the administration of ketorolac (n = 31). (B) Progression-free survival in patients with NLR ≤ 3,53 according to the administration of ketorolac (n = 135).
Figure 5
Figure 5
Progression-free survival according to the preoperative NLR and the influence of ketorolac administration during the surgery. (A) Disease-free survival in patients with NLR > 3,53 according to the administration of ketorolac (n = 31). (B) Progression-free survival in patients with NLR ≤ 3,53 according to the administration of ketorolac (n = 135).
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