Tumor Size Emerges as Key Prognostic Factor in FIGO 2018 Stage IIIC Cervical Cancer

A new retrospective study from Mersin University in Turkey adds fresh weight to a growing debate in gynecologic oncology: whether the 2018 revision of the FIGO staging system for cervical cancer has created a stage IIIC category so broad that it lumps together patients with dramatically different prognoses. The research, published in the Journal of Cancer Research and Clinical Oncology, followed 144 patients treated at a single center between 2015 and 2025 and found that tumor size, measured in millimeters, behaved as an independent predictor of survival, with every additional millimeter of tumor diameter corresponding to a 6.4 percent increase in the risk of death. The finding suggests that the 4-centimeter threshold long used to separate early from locally advanced disease may still carry decisive prognostic meaning even after lymph node status is folded into the stage designation.

The FIGO staging system is the international standard for classifying cervical cancer, and its 2018 revision marked the most substantial overhaul in two decades. Under the previous 2009 framework, stage III disease was defined primarily by tumor extension to the pelvic sidewall or lower vagina and by hydronephrosis, while lymph node involvement was recorded separately and did not alter the stage. The 2018 revision changed that logic fundamentally. Any patient with proven pelvic or para-aortic lymph node metastasis, regardless of tumor dimensions, is now assigned to stage IIIC, subdivided into IIIC1 for pelvic nodes and IIIC2 for para-aortic involvement. The intention was to acknowledge the strong adverse prognostic weight of nodal disease and to bring imaging and pathology into the staging process, which previously relied on clinical examination alone.

That change, however, produced an unintended consequence that clinicians have been discussing ever since. A small tumor confined to the cervix with a single positive pelvic node and a bulky tumor invading the pelvic sidewall now share the same stage IIIC label, despite representing biologically and therapeutically distinct situations. Critics of the revision argued that the new category might obscure meaningful differences in outcome, complicating both treatment planning and the interpretation of clinical trials. The Mersin team, led by Hatice Banu Atay of the Department of Gynecologic Oncology, set out to quantify exactly how much heterogeneity the new system introduced and to test whether simple, routinely measured variables such as tumor diameter could restore prognostic clarity within the stage IIIC group.

The investigators retrospectively re-staged 212 consecutive patients with cervical cancer treated at Mersin University and affiliated hospitals between 2015 and 2025. After exclusions, 144 patients formed the final cohort, with a mean age of 54.5 years and a mean tumor diameter of 42.5 millimeters. Squamous cell carcinoma, the histologic type most closely linked to persistent human papillomavirus infection, accounted for 110 cases, or 76.4 percent of the cohort. From this group, 109 patients with early-stage disease under the older 2009 system, specifically stages IB and IIA/B, were analyzed in multivariate Cox regression models, while survival differences between the 2009 and 2018 stage III definitions were assessed with Kaplan-Meier curves and log-rank tests.

The survival contrast between the two staging eras was striking. Median survival for patients classified as stage III under FIGO 2009 was 26 months, whereas under the 2018 system the median survival for the corresponding stage III group rose to 74 months. The nearly threefold difference illustrates how the reclassification diluted the stage III category: patients with relatively favorable features, such as small primary tumors with limited nodal spread, were pulled into a stage that had previously been reserved for locally advanced disease. In other words, the same Roman numeral now describes a much more heterogeneous population, and the average outcome attached to that numeral has improved accordingly, without any change in the underlying biology or treatment.

Within the early-stage subgroup, tumor size emerged as the variable that mattered most. In the Cox regression analysis, each 1-millimeter increase in tumor diameter carried a hazard ratio of 1.064, with a 95 percent confidence interval of 1.022 to 1.108 and a p-value of 0.003, confirming an independent effect on mortality. Lymph node positivity, by contrast, was significant in univariate analysis but lost its independent prognostic value once tumor size and other factors were accounted for in multivariate models. This inversion of the expected hierarchy is notable, because nodal status was the principal rationale for creating stage IIIC in the first place. The authors caution, however, that the modest sample size limits the statistical power available to detect all but the strongest effects.

When the investigators stratified outcomes at the conventional 4-centimeter cutoff, the pattern became clearer. Patients assigned to stage IIIC under the 2018 system whose tumors measured 4 centimeters or smaller showed survival comparable to that of patients with stage I to II disease, while tumors larger than 4 centimeters predicted substantially worse outcomes. This observation supports the idea that the 4-centimeter boundary, which FIGO retained in its definitions of stage IB2, IB3 and IIA2, continues to separate two prognostically distinct populations even within the redefined stage IIIC. A small tumor with nodal involvement may behave far more like early-stage disease than like classic locally advanced cancer, a distinction with potential implications for how intensively such patients are treated and how they are counseled.

The authors are careful to frame these findings as hypothesis-generating rather than practice-changing. The stage IIIC subgroup with tumors of 4 centimeters or smaller contained only 11 patients, and no deaths were recorded in that group during follow-up, which makes any conclusion about its favorable prognosis inherently fragile. The retrospective, single-center design introduces further limitations, including the possibility of selection bias and variability in treatment protocols across the decade covered by the study. The team emphasizes that validation in larger, multicenter cohorts with standardized treatment regimens will be essential before any modification to staging or treatment algorithms could be considered on the basis of these results.

Even with those caveats, the study makes a meaningful contribution to an international conversation about how cervical cancer should be classified in the era of high-quality imaging and molecular profiling. By quantifying the survival gap between the 2009 and 2018 stage III definitions and by demonstrating the independent prognostic weight of tumor size, the Mersin data provide empirical support for proposals to subdivide stage IIIC further, perhaps incorporating tumor diameter as a formal staging parameter. The authors also note that their results feed into a national dataset and offer comparability with international standards, laying groundwork for future staging revisions and collaborative research. For clinicians managing cervical cancer today, the practical message is that the stage IIIC label should not be read in isolation: within it, a 3-centimeter tumor and a 7-centimeter tumor may represent very different diseases, and treatment intensity, trial stratification and prognostic counseling should reflect that reality. As cervical cancer remains a leading cause of cancer death among women worldwide, particularly in regions with limited screening infrastructure, refining the tools used to predict individual outcomes is not an academic exercise but a matter of clinical urgency.

Subject of Research: Prognostic heterogeneity of FIGO 2018 stage IIIC cervical cancer and the role of tumor size as an independent survival predictor

Article Title: Stage IIIC heterogeneity in FIGO 2018 cervical cancer staging: a retrospective single-center study on tumor size as an ındependent prognostic factor

Article References: Atay, H. B., Gokulu, S. G., Kıllı, M. C., Karagun, S., Gokay, D. Z., & Yıldırım, Y. (2026). Stage IIIC heterogeneity in FIGO 2018 cervical cancer staging: a retrospective single-center study on tumor size as an ındependent prognostic factor. Journal of Cancer Research and Clinical Oncology. https://doi.org/10.1007/s00432-026-06602-w

Image Credits: AI Generated

DOI: 10.1007/s00432-026-06602-w

Keywords: cervical cancer, FIGO 2018 staging, stage IIIC, tumor size, prognosis, lymph node metastasis, survival analysis, gynecologic oncology, Cox regression, cancer staging, squamous cell carcinoma, retrospective study