Introduction

The introduction of cervical cancer screening and HPV vaccination has led to a remarkable reduction in cervical cancer rates in developed countries.1 Despite this progress, cervical cancer continues to be a major concern, claiming its place as the fourth most common cancer among women worldwide. In 2020alone, there were a staggering 604,127 new cases and 341,831 deaths attributed to this disease.2 Metastatic disease typically indicates a poor prognosis from diagnosis. Predicting prognosis is essential for effective treatment strategies. However, current prognostic factors are not accurate in predicting outcomes. Obesity increases the likelihood of developing and dying from several types of cancer, such as endometrial, breast, colon, ovarian, and pancreatic cancers.3 Likewise, obesity is also a well-known risk factor for cervical cancer, but the relationship between disease characteristics, outcomes, and obesity remains controversial.4 The nutritional status of cancer patients is a crucial component that significantly affects their quality of life. Although the issues of cachexia and unintentional weight loss in cancer have been widely acknowledged, the rising rates of obesity among adults in the United States complicate our understanding of how body weight impacts cancer outcomes. Understanding this relationship is essential for improving cancer patient care.5 Research shows that a higher body mass index (BMI) is associated with elevated cancer death rates, yet the relationship between BMI and survival rates in cervical cancer is still unclear.3,4 Obesity has been associated with worse survival outcomes in patients with non-metastatic cervical cancer in some studies. In another trial, BMI was not predictive of PFS in this endometrial cancer population although morbidly obese patients had decreased OS in primary Stage III/IV patients.6 In the literature, in patients with metastatic cervical cancer, limited data are available regarding the impact of BMI on patients’ outcome, although treatment strategies and prognostic factors have recently been reviewed.7

Obesity may influence cancer progression through several biological mechanisms, including chronic systemic inflammation, insulin resistance, altered adipokine secretion, and increased insulin-like growth factor-1 (IGF-1) signaling. However, the relationship between BMI and survival outcomes in cervical cancer remains controversial. Some studies have reported worse outcomes among obese patients, whereas others have suggested a potential “obesity paradox”, in which overweight patients experience more favorable survival outcomes. Furthermore, evidence specifically addressing patients with metastatic cervical cancer remains limited. It should also be noted that BMI is an imperfect surrogate of nutritional status because it does not distinguish adipose tissue from skeletal muscle mass or account for body composition differences.

The primary objective of our study was to evaluate the effect of BMI on survival outcomes in women with metastatic cervical cancer.

Materials and Methods

This retrospective study was conducted at the Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey. This study included 60 women with histologically confirmed metastatic cervical cancer between February 2014 and January 2024. This study was approved by the Ethics Committee of Bakirkoy Dr. Sadi Konuk Training and Research Hospital (2025/63) by the precepts established by the Declaration of Helsinki; Due to the retrospective nature of the study, the requirement for written informed consent was waived by the ethics committee. Patient characteristics, demographics, clinical, pathological data, and BMI were abstracted from electronic medical records at the time of treatment start. Inclusion criteria were: female patients aged ≥18 years, histologically confirmed cervical cancer, radiologically or pathologically confirmed metastatic disease, receipt of systemic treatment at our institution, and availability of baseline height and weight measurements for BMI calculation. Exclusion criteria were: missing BMI data at treatment initiation, incomplete clinical records, concurrent malignancies, and participation in ongoing clinical trials during the study period. Patients with missing baseline BMI data were excluded from the study. No imputation methods were applied, and all analyses were performed using complete-case data. First-line treatment consisted primarily of paclitaxel-platinum chemotherapy with or without bevacizumab.

BMI values at treatment initiation start were calculated for all patients using the formula BMI = weight (kg) / height (m2), and classified according to the World Health Organization categories of underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5 to <25 kg/m2), overweight (BMI 25 to <30 kg/m2), and obese (BMI ≥30 kg/m2). Additionally, patients were divided into two groups: high BMI (≥25) and low BMI (<25). Tumor response was assessed clinically by conventional imaging every 3 months after treatment. According to RECIST 1.1, PFS was defined as the time from starting treatment until disease progression. OS was defined as the time from starting treatment until death; patients who were still alive or lost to follow-up at the data cutoff were censored at the date of the last follow-up. The final follow-up was conducted in January 2025.

Statistical analyses were performed using IBM SPSS Statistics version 25 running on Microsoft Windows 10. Cox regression modeling explored associations between BMI and time-to-event outcomes, including PFS and OS. The Kaplan–Meier method was used to estimate PFS and OS curves. The Log rank test was used to test for differences between curve estimates. Parametric modeling obtained BMI hazard ratios with 95% confidence intervals while controlling for age, stage, and histology. A chi-squared test, with Fisher’s exact test as appropriate, was used to test two-group and/or nominal categorical variable comparisons. Multivariable Cox proportional hazards models were adjusted for clinically relevant covariates including age, histological subtype, ECOG performance status, and metastatic burden. And a p-value of <0.05 was considered statistically significant.

Results Patient Characteristics

A total of 65 patients with cervical cancer were identified during the study timeframe. Five (7.6%) patients did not have data available for BMI calculation at the time of initial presentation (diagnosis) and thus were excluded from the analysis.

The baseline characteristics of the patients are described in Table 1. The median age of the remaining60 patients was 61.5 (range 32–84). Histological features were squamous carcinoma in 80.0% and adenocarcinoma in 20.0% of biopsies. Surgery was performed in 16.6% of the patients, and de novo metastasis was present in 55%. ECOG-PS was 0 in 75.0% and 1 in 25.0% of the patients. Soft tissue metastasis was 63.3%, lung 28.3%, liver 18.3%, and bone metastasis 11.6% in the patients.BMI classified patients as obese (30.0%), overweight (31.7%), and normal weight or underweight (38.3%). 30.0% of the cohort were classified as having low BMI (<25), and 70.0% of the cohort had high BMI (≥25).

Table 1 Patient Characteristics

Progression-Free Survival

Median follow-up duration was 13.0 months (1–105 months). There were no statistically differences in 2-year and 5-year PFS according to age (p=0.659), histological type (p = 0.807), surgical history (p = 0.367), presence of de novo metastases (p = 0.452), and metastasis site of the patients (p = 0.265).PFS was better in patients with ECOG-PS 0 (p = 0.041) (Table 2).

Table 2 Univariate and Multivariate Analysis for Progression Free Survival

The Log rank test was significant, suggesting a survival advantage for normal-weight patients at treatment start, compared to overweight and obese patients. The 2-year and 5-year PFS were 10.2%, 10.0% in obese patients, 9.2%, 9.2% in overweight, 35.9%, 33.4% in normal or underweight (p = 0.048).The 2-year and 5-year PFS rates, respectively, were 9.0%, 4.5% (95% CI) for patients with high BMI (≥25) vs 35.9%, 34.4% (95% CI) for patients with low BMI (<25) (p = 0.037) (Figure 1). In multivariable analysis, high BMI remained independently associated with worse PFS (HR=1.87, 95% CI=1.01–3.66, p=0.045).

Figure 1 Kaplan–Meier curve for progression-free survival according to BMI group (<25 vs ≥25 kg/m2).

Overall Survival

There were no statistically differences in 2-year and 5-year OS according to age (p = 0.243), histological type (p = 0.131), surgical history (p = 0.108), presence of denovo metastases (p =0.256), ECOG-PS (p =0.157), metastasis site of the patients (p = 0.116) (Table 3).

Table 3 Univariate and Multivariate Analysis for Overall Survival

The Log rank test was significant (p <0.001), suggesting a survival advantage for normal-weight patients at treatment start, compared to overweight and obese patients. The 2-year and 5-year OS was 34.7%, 24.6% in obese patients, 13.8%, 13.8% in overweight, 55.0%, 44.0% in normal or underweight (p =0.032). The 2-year and 5-year OS rates, respectively, were 22.2%, 17.8% (95% CI) for patients with high BMI (≥25) vs 55.0%, 44.0% (95% CI) for patients with low BMI (<25) (p = 0.024) (Figure 2). In multivariate regression analyses, high BMI was independently associated with poorer OS (HR=2.55, 95% CI=1.18–5.50, p=0.017).

Figure 2 Kaplan–Meier curve for overall survival according to BMI group (<25 vs ≥25 kg/m2).

Discussion

When analyzing the impact of BMI on cervical cancer outcomes, it is crucial to acknowledge that both extremes of weight seem to have a detrimental influence on survival. The study conducted by Kizer et al examined patients who were undergoing definitive chemoradiation for early-stage cervical cancer. The authors discovered that the median 5-year survival rate was substantially lower in patients with a BMI<18.5 kg/m2 (33%) compared to normal weight (BMI 18.5–24.9 kg/m2) and overweight/obese patients (BMI≥25 kg/m2) at 60% and 68%, respectively.8 They initially concluded that a higher BMI could provide some protective benefits. However, compelling evidence from a recent large-scale study at MD Anderson has challenged this notion, revealing that morbidly obese patients (BMI>35 kg/m2) face the most detrimental disease-specific survival rates.4 A meta-analysis found that women with gynecological cancers and a BMI of ≥30 kg/m2 do not improve survival outcomes compared to those with a BMI of <30 kg/m2.9 It was discovered in another trial that morbid obesity was associated with a poorer disease-specific survival in women who had locally advanced cervical cancer.4 In the other trial; Clark et al showed that overweight and obesity were associated with worse survival in patients with locally advanced cervical cancer.10 Our data support the theory that high BMI is associated with poor prognosis and show that increasing weight is not protective. Rather, overweight and obese patients in our cohort did worse than their normal weight counterparts. These findings are also supported by more recent evidence demonstrating BMI as an independent prognostic factor in patients with cervical cancer.11

Chronic systemic inflammation is a potential hypothesis that interconnects poor cancer prognosis with extreme weight. Individuals who are overweight or obese are often in a state of increased inflammation, which can significantly raise cell proliferation while also suppressing the natural process of apoptosis.12 Chronic inflammation secondary to obesity can significantly disrupt the tissue microenvironment generating conditions that have pro-tumorigenic effects. The presence of insulin resistance, elevated insulin and insulin-like growth factor (IGF-1) levels, along with increased leptin and decreased adiponectin levels linked to excess body fat, creates a favorable environment for tumor development.13 It is probable that this is not the only reason for the unfavorable outcomes. Especially in morbid obese patients, the presence of co-morbid medical conditions significantly impacts survival rates. On the other hand, there may be a disparity in the medical care that overweight and obese patients receive compared to normal-weight patients.10 A substantial technical challenge may arise when performing radical surgery on obese patients with cervical cancer. Surgeons often approach the decision to perform a radical hysterectomy on obese patients with caution. This reluctance stems from valid concerns regarding higher risks of complications during surgery, the presence of additional health issues, and the inherent challenges of operating on individuals with obesity. This may have prevented some early-stage patients from receiving optimal treatment and thus worsened the prognosis. However, we did not find an association between surgical history and survival outcomes.

In addition, chemotherapy doses are calculated based on body surface area, not based on weight, and most clinicians also prefer not to exceed 2 m2. This condition can lead to undertreatment in obese patients, worsening the consequences.

Despite these limitations, this study shows that the extremes of weight are detrimental to survival in women with cervical cancer, and further investigation regarding the cause of poor prognosis is warranted. Interventions that target nutritional counseling and physical activity should be explored in these populations.

We acknowledge some limitations in our study. Firstly, the retrospective design of this cohort study brings with it inherent limitations and potential biases. The relatively small sample size may have limited statistical power and increased the risk of type II error. Therefore, some potentially relevant associations may not have been detected. Since all patients in this cohort are from a single institution, the results may not be widely generalizable. Furthermore, treatment approaches may have varied among patients during the study period, potentially contributing to outcome heterogeneity despite adjustment for major clinical covariates. Another limitation is the relatively short median follow-up duration. Although 5-year survival rates were estimated using Kaplan–Meier methods, these long-term estimates should be interpreted cautiously because of the limited follow-up available for a substantial proportion of patients. Additionally, using BMI alone does not effectively estimate muscle mass and adiposity in women, which prevents a direct interpretation of our findings in the underweight population.

Conclusion

This study suggests that higher BMI is associated with poorer survival outcomes in women with metastatic cervical cancer. Further research is needed to better understand the mechanisms underlying this association. BMI may represent a clinically relevant prognostic marker in this patient population. Given the retrospective observational design and relatively small sample size of this study, the observed associations should not be interpreted as causal relationships. Rather, these findings should be considered exploratory and hypothesis-generating and warrant validation in larger prospective multicenter studies.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request and with permission of the institutional ethics committee.

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Bakirkoy Dr. Sadi Konuk Training and Research Hospital (2025/63). All patient data were anonymized before analysis, and confidentiality was maintained throughout the study in accordance with institutional and ethical guidelines. Due to the retrospective nature of the study, the requirement for written informed consent was waived by the ethics committee.

Informed Consent Statement

Patient consent was waived due to the retrospective design of the study.

Author Contributions

MY and RC researched literature and conceived the study. CK and SYT wrote the first draft of the manuscript. ED revised it critically for important intellectual content. All authors reviewed and edited the manuscript and approved the final version of the manuscript. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Disclosure

The authors declare no conflicts of interest.

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