CT-to-surgery interval and occult nodal metastasis in cN0 oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck, and its management hinges on a deceptively simple question: has the cancer already spread to the lymph nodes of the neck? For patients whose necks appear clean on clinical examination and imaging — the so-called clinically node-negative, or cN0, neck — surgeons must decide whether to perform an elective neck dissection or wait. Computed tomography (CT) is a mainstay of this staging process, but its sensitivity for detecting small nodal deposits is limited, and occult nodal metastasis remains a persistent clinical challenge. Now, a new retrospective study from Technical University of Munich has examined whether the interval between CT staging and surgery influences the likelihood of finding hidden cancer in the lymph nodes, offering some reassurance that routine delays are not strongly linked to occult spread — while flagging a small subgroup of patients whose substantially prolonged intervals warrant closer scrutiny.

The study, published in the Journal of Cancer Research and Clinical Oncology, analyzed 329 patients with primary cN0 OSCC who underwent CT staging and neck dissection between 2011 and 2024. The researchers, led by Jannik Ketschau and Lucas M. Ritschl of the Department of Oral and Maxillofacial Surgery at TUM University Hospital Klinikum Rechts der Isar, set out to determine whether the time elapsed between the diagnostic CT scan and the operation had any measurable effect on pathological nodal outcome. The question is clinically important because staging CT scans are typically performed days or weeks before surgery, and if tumor cells were seeding new lymph node deposits during that window, one might expect longer intervals to correlate with higher rates of nodal positivity. The team also examined whether the interval influenced the total number of lymph nodes removed and the presence of extranodal extension (ENE), a feature in which cancer cells breach the lymph node capsule and which carries significant prognostic weight.

The median CT-to-surgery interval in the cohort was 9.0 days, with an interquartile range of 5.0 to 15.0 days — meaning most patients underwent surgery within roughly two weeks of their scan. Overall, 53 patients, or 16.1 percent of the cohort, had lymph node metastasis on final pathology. In the initial univariable analysis, the interval was associated with lymph node positivity, with an odds ratio of 1.031 per additional day (p = 0.035). On the surface, this suggested that each extra day between CT and surgery modestly increased the odds of finding occult nodal disease. However, when the researchers adjusted for age and smoking status — two well-established confounders in head and neck oncology — the association weakened and lost statistical significance (OR 1.027, p = 0.065). A similar pattern emerged for lymph node count, which showed a comparable but non-significant association (incidence rate ratio 1.027, p = 0.068).

The team then deployed a battery of sensitivity analyses to test whether the initially significant finding was robust. They stratified patients into quartiles of CT-to-surgery interval, excluded extreme intervals, and adjusted for lymph node yield — the total number of lymph nodes retrieved during neck dissection, which itself reflects surgical technique and can influence the apparent rate of nodal detection. The association with nodal positivity failed every test. Across interval quartiles, the relationship was essentially flat (p = 0.969). After excluding intervals longer than 30 days, the odds ratio dropped to 0.995 (p = 0.824), indicating no meaningful effect among patients operated on within a month of their scan. After adjustment for lymph node yield, the association was similarly non-significant (OR 1.015, p = 0.334). In other words, the initially significant unadjusted result was not a stable signal but a fragile one that dissolved under closer statistical scrutiny.

Yet the data contained one notable exception. Among the 13 patients whose CT-to-surgery interval exceeded 30 days, the rate of nodal positivity was dramatically higher than in those with shorter intervals — 53.8 percent versus 14.6 percent. This finding, while striking, comes with important caveats. The subgroup is small, and the retrospective design cannot determine whether the prolonged interval itself contributed to nodal spread or whether these patients’ delays reflected other factors — such as more complex clinical presentations, comorbidities requiring optimization, or logistical barriers — that independently correlated with more aggressive disease biology. The researchers were careful to note that this observation warrants further investigation rather than serving as definitive evidence that delayed surgery causes occult metastasis.

The interval was not associated with extranodal extension (p = 0.740), suggesting that even among patients who did have nodal disease, the time elapsed between CT and surgery did not appear to influence whether cancer cells had breached the lymph node capsule. Tumor localization within the oral cavity was likewise not associated with nodal positivity (p = 0.175), indicating that the site of the primary tumor did not systematically alter the relationship between interval and occult spread. These null findings add to the overall reassurance offered by the study: within the range of intervals typically encountered in clinical practice, the CT-to-surgery window does not appear to be a major driver of occult nodal disease or its most concerning features.

The technical approach underlying the study reflects contemporary standards in surgical oncology research. By using logistic regression for binary outcomes such as nodal positivity and negative binomial regression for count outcomes such as lymph node number, the researchers applied statistical models appropriate to the data structure. The inclusion of sensitivity analyses — quartile stratification, exclusion of extreme intervals, and lymph node yield adjustment — demonstrates the kind of methodological rigor increasingly expected in retrospective surgical studies, where unadjusted associations can easily mislead. The fact that the initially significant unadjusted result was confined to a small subgroup with substantially prolonged intervals, rather than being a consistent gradient across the full range of intervals, is a key interpretive point: it suggests that routine clinical delays of days to a couple of weeks are not strongly linked to occult nodal metastasis, while substantially delayed surgery remains an open question.

For clinicians managing cN0 OSCC, the study offers practical reassurance. The decision to perform an elective neck dissection in a clinically node-negative neck is already contentious, balancing the morbidity of the procedure against the risk of leaving hidden disease untreated. If the CT-to-surgery interval were strongly associated with occult metastasis, it would add urgency to surgical scheduling and potentially influence staging protocols. The Munich data suggest that, within typical intervals, this concern is not strongly supported — the interval is not a major independent risk factor for occult nodal disease. However, the finding that patients with intervals exceeding 30 days had substantially higher rates of nodal positivity — albeit in a very small subgroup — suggests that substantially delayed surgery may warrant closer attention, whether through repeat imaging, expedited scheduling, or heightened clinical vigilance.

The study also highlights the persistent limitations of CT-based staging in the cN0 neck. Despite advances in imaging technology, CT sensitivity for detecting small nodal deposits remains limited, and occult metastasis rates in cN0 OSCC continue to be clinically significant. The 16.1 percent rate of nodal positivity in this cohort — despite all patients having been staged as node-negative on CT — underscores this diagnostic gap. As imaging modalities evolve and molecular diagnostics advance, the hope is that the detection of occult disease will improve, reducing the reliance on elective neck dissection for patients whose nodal status remains uncertain. Until then, studies like this one provide valuable evidence about which clinical variables do — and do not — meaningfully influence the risk of hidden spread, helping surgeons and oncologists refine their approach to one of head and neck oncology’s most enduring challenges.

Subject of Research: CT-to-surgery interval and occult nodal metastasis in cN0 oral squamous cell carcinoma

Article Title: CT-to-surgery interval and occult nodal metastasis in cN0 oral squamous cell carcinoma

Article References: Ketschau, J., Mohr, J., Grabenhorst, A., Singer, H., Richter, H., Krautkremer, N., Niu, M., Pippich, K., Stimmer, H., Graf, M., Wolff, K.-D., & Ritschl, L. M. (2026). CT-to-surgery interval and occult nodal metastasis in cN0 oral squamous cell carcinoma. Journal of Cancer Research and Clinical Oncology. https://doi.org/10.1007/s00432-026-06642-2

Image Credits: AI Generated

DOI: 10.1007/s00432-026-06642-2

Keywords: CT-to-surgery, interval, occult, nodal, metastasis, oral, squamous, cell, carcinoma, scientific research