Study: NLR, PLR May Be Early Prognostic Markers for Patients With Ovarian Cancer

A high neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are both associated with worse progression-free survival (PFS) and 5-year overall survival (OS) in patients with ovarian cancer, according to a review published in the Asian Pacific Journal of Cancer Prevention.¹

The researchers explained that there are approximately 200,000 new ovarian cancer cases annually; that number is expected to increase to 371,000 new annual cases by 2035. Also, ovarian cancer has a mortality rate of 6.3 per 100,000 women annually, making it one of the deadliest, most challenging cancers to treat.

They explained that ovarian cancer is called the “silent killer” because patients frequently do not show symptoms until reaching an advanced stage; roughly 80% of ovarian cancer cases are detected in later stages when it has spread beyond the ovaries.² Therefore, the researchers noted that earlier diagnoses are crucial for patients with ovarian cancer.

With the help of standard parameters, clinicians can identify the disease and start treatment earlier. Past studies found that ovarian cancer cells trigger systemic inflammatory activation, which precedes tumor development by promoting cancer cell proliferation and metastasis or aiding angiogenesis; this inflammatory response is linked to the initiation, progression, and spread of cancer.^3,4 Because of this, the researchers systemically searched data on inflammatory markers, namely the NLR and PLR, to investigate their association with the OS and PFS of patients with ovarian cancer.¹

High neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are associated with worse progression-free survival (PFS) and 5-year overall survival (OS) in patients with ovarian cancer (OC). | Image Credit: Orawan - stock.adobe.com

The researchers searched for eligible studies in the Science Direct, PubMed, Cochrane Library, and Google Scholar databases from 2002 to 2023 using various keywords, including “ovarian cancer,” “platelets lymphocyte ratio,” and “neutrophil lymphocyte ratio.” Afterward, they performed a manual search by reviewing the references of all eligible studies.

For studies to be included in the review, they had to align with the researchers’ inclusion criteria. For example, they needed to be English, full-text studies that examined the significance of pre-treatment NLR or PLR parameters as ovarian cancer prognostic markers.

From each eligible study, the researchers extracted various information, like the design, methodology, NLR and PLR values, and OS and PFS values; in cases of unclear or missing data, the researchers contacted the original publication authors via email for clarification.

Their initial search yielded 1255 relevant studies. However, after examining them more closely, the researchers only included 16 studies. Most were retrospective, observational studies that analyzed Asian patients; the researchers analyzed 3862 patients across the 16 studies, and 2793 were of Asian descent. The mean patient age was 50.6 years, with a mean follow-up of 45.8 months.

By analyzing 7 multivariate studies, the researchers determined that patients with higher NLR had worse PFS (HR, 1.35; 95% CI, 1.05-1.74; I² = 74%). As for the relationship between PLR and PFS in patients with ovarian cancer, 6 multivariate studies showed that patients with high PLR have significantly worse PFS (HR, 1.62; 95% CI, 1.56-3.09; I² = 87%).

Additionally, across 9 multivariate studies, a correlation was identified between higher NLR and worsening OS (HR, 1.46; 95% CI, 1.42-4.35; I² = 90%). Lastly, through 7 multivariate studies, the researchers discovered that higher PLR correlated with worse OS (HR, 1.66; 95% CI, 1.12-2.46; I² = 88%). Therefore, among patients with ovarian cancer, both high NLR and PLR are associated with worse PFS and 5-year OS.

The researchers acknowledged their limitations, one being that the studies included are retrospective and have relatively small sample sizes. Also, most patients analyzed were Asian, meaning these results may not be generalizable to other populations. Despite these limitations, the researchers expressed confidence in their findings and suggested areas for future research.

“Our analysis suggests that NLR/PLR could be utilized as an early prognostic marker for ovarian cancer patients,” the authors concluded. “However, a more extensive study which included a greater number of publications, as well as studies with a prospective design, are needed to obtain more conclusive results.”

References

1. Winata IGS, Pradnyana IWAS, Yusrika MU, Pradnyaandara IGBMA, Pradnyadevi PAS. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as an early prognostic marker in patients with ovarian cancer: a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2024;25(6):1921-1927. Published 2024 Jun 1. doi:10.31557/APJCP.2024.25.6.1921
2. Nersesian S, Glazebrook H, Toulany J, Grantham SR, Boudreau JE. Naturally killing the silent killer: NK cell-based immunotherapy for ovarian cancer. Front Immunol. 2019;10:1782. Published 2019 Aug 9. doi:10.3389/fimmu.2019.01782
3. Chon S, Lee S, Jeong D, Lim S, Lee K, Shin J. Elevated platelet lymphocyte ratio is a poor prognostic factor in advanced epithelial ovarian cancer. J Gynecol Obstet Hum Reprod. 2021;50(6):101849. doi:10.1016/j.jogoh.2020.101849
4. Hainaut P, Plymoth A. Targeting the hallmarks of cancer: towards a rational approach to next-generation cancer therapy. Curr Opin Oncol. 2013;25(1):50-51. doi:10.1097/CCO.0b013e32835b651e