Diagnostic capabilities of [ 18 F]FDG PET/CT in cases of endometrial cancer: comparison with the results of morphological examination

E. E. Komlichenko; Комличенко Э. Э.; E. V. Lanskaya; Ланская Е. В.; E. L. Dikareva; Дикарева Е. Л.; E. V. Komlichenko; Комличенко Э. В.; E. G. Koshevaya; Кошевая Е. Г.; L. B. Mitrofanova; Митрофанова Л. Б.; G. A. Raskin; Раскин Г. А.; E. A. Ulrikh; Ульрих Е. А.; D. V. Ryzhkova; Рыжкова Д. В.

doi:10.35693/SIM707679

Diagnostic capabilities of [¹⁸F]FDG PET/CT in cases of endometrial cancer: comparison with the results of morphological examination

Authors: Komlichenko E.E.¹, Lanskaya E.V.¹, Dikareva E.L.¹, Komlichenko E.V.¹, Koshevaya E.G.¹, Mitrofanova L.B.¹, Raskin G.A.², Ulrikh E.A.¹, Ryzhkova D.V.¹
Affiliations:
1. Almazov National Medical Research Centre
2. Diagnostic and Treatment Center of the International Institute of Biological Systems named after Sergey Berezin
Issue: Vol 11, No 3 (2026)
Pages: 227-232
Section: Oncology and radiotherapy
Published: 09.06.2026
URL: https://innoscience.ru/2500-1388/article/view/707679
DOI: https://doi.org/10.35693/SIM707679
ID: 707679

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Abstract

Background. Endometrial cancer is a common oncological disease of the female reproductive system. Treatment is based on a comprehensive analysis of FIGO staging, degree of differentiation, invasion, and molecular genetic profile of the tumor.

Aim: comparative analysis of the metabolic characteristics of the primary tumor based on PET/CT results with [¹⁸F]FDG and key prognostic factors of endometrial cancer according to morphological and immunohistochemical studies.

Material and methods. A retrospective analysis of 34 patients with morphologically verified endometrial cancer who underwent PET/CT prior to surgical treatment with [¹⁸F]FDG. The relationship between the quantitative metabolic characteristics of the primary tumor: the standardized accumulation level (SUVmax), the metabolic volume of the tumor (MTV) and the total glycolytic index (TLG) of the primary tumor with the histological type, degree of differentiation (Grade), the depth of invasion into the myometrium, the presence of lymphovascular invasion and damage to the lymph nodes was investigated.

Results. A statistically significant strong positive correlation was found between SUVmax and the degree of neoplasm anaplasia (ρ = 0.68, p < 0.001). The SUVmax values significantly differed between the Grade groups: Grade 1, 7.25, Grade 2, 7.22 and Grade 3, 12.80 (p < 0.001). Non-endometrioid histological types and the presence of LVI were also associated with higher values of SUVmax, MTV, and TLG. A moderate positive correlation of SUVmax with the depth of tumor invasion into the myometrium was found (ρ = 0.58, p = 0.001).

Conclusion: quantitative metabolic characteristics of the primary tumor obtained by PET/CT scans with [¹⁸F]FDG can be used for predictive risk stratification as part of a personalized approach to endometrial cancer treatment, as they are closely related to the main histopathological prognostic factors of biological tumor aggressiveness.

Keywords

endometrial cancer, PET/CT scan with [18F]FDG, metabolic volume of the tumor, degree of differentiation, depth of invasion into the myometrium, lymphovascular invasion

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INTRODUCTION

Endometrial cancer (EC) leads in the structure of oncological diseases of the female reproductive system [1–3]. In the era of personalized medicine, the choice of treatment tactics is based on a complex integration of classic clinical and morphological prognostic factors (FIGO stage, histological type, degree of differentiation, depth of invasion in the myometrium, lymph-vascular invasion) and molecular genetic profile of the tumor [4, 5].

Traditionally, the principal method of radiological diagnosis of EC has been magnetic resonance imaging (MRI) with its high soft-tissue contrast resolution, enables accurate evaluation of the depth of myometrial invasion. Positron emission tomography combined with computed tomography (PET/CT) enhanced with radiopharmaceutical ¹⁸F-fluorodesoxyglucose ([¹⁸F]FDG) is widely used in the advanced stages of the disease to evaluate the volume of the total tumor burden, identification of extrauterine extension and metastases, as well as for risk stratification. PET/CT is a highly informative method of preoperative staging making it possible to evaluate the metabolic activity not only of the primary tumor but also of possible metastases [6–9].

The following are the special features of the 2023 FIGO staging of cancer of the endometrium: division into the non-aggressive histological type (Low-grade), including Grade 1 and 2 endometrial adenocarcinoma and mucinous adenocarcinoma, and the aggressive type (High-grade): Grade 3 endometrial adenocarcinoma, serous, clear cell, undifferentiated, mixed, mesonephric-like, gastrointestinal-type carcinomas, and carcinosarcomas; evaluation of the myometrial invasion; evaluation of lymph-vascular invasion, identification of molecular genetic tumor subtypes [10]. These factors collectively determine and characterize the biological nature of endometrial tumors, affecting disease stage, clinical course, long-term outcomes, and development of therapeutic strategy. To date, no comprehensive studies comparing PET/CT data with all of the above-mentioned endometrial cancer characteristics according to the updated FIGO classification are available in either Russian or international literature.

AIM

Comparative analysis of the metabolic characteristics of the primary tumor based on PET/CT results with [¹⁸F]FDG and key prognostic factors of endometrial cancer according to morphological and immunohistochemical studies.

MATERIAL AND METHODS

A retrospective single-center study was conducted, enrolling 34 patients with morphologically confirmed endometrial cancer who underwent radical surgical treatment. The cohort comprised 34 patients aged 43 to 86 years (median 63 years). All patients underwent morphological and immunohistochemical examination of the surgical specimens.

[18F]FDG PET/CT was performed strictly on an empty stomach. The calculated activity of the radiopharmaceutical was 3–5 MBq/kg body weight (mean 300–550 MBq). PET/CT data acquisition was initiated 60 minutes after radiopharmaceutical injection and was carried out according to the standard whole-body protocol on a Discovery 710 PET/CT scanner (General Electric, USA). The iterative reconstruction of the image was performed automatically using the ordered subset expectation maximization (OSEM) algorithm. Post-processing of the obtained results included a visual analysis of PET and X-ray computed tomograms and stacked images using the software of the AW Volume Share 6 (AW4.6) workstation. Uptake of the radiopharmaceutical in the primary neoplasms and metastases was considered PET-positive if its intensity exceeded background values in the surrounding tissues or contralateral regions.

To obtain quantitative metabolic characteristics of the primary tumor, areas of interest were outlined automatically on PET images in the axial plane under visual control with subsequent manual correction in order to exclude from the target volume any areas with physiological uptake of the radiopharmaceutical. The maximum standardized uptake volume of the radiopharmaceutical (SUVmax), total tumor lesion glycolysis (ТLG) and metabolic tumor volume (MTV) with cutoff threshold at SUV > 41% from SUVmax were automatically calculated on the workstation and used for the quantitative assessment of [18F]FDG uptake intensity in the primary tumor nidus.

All the patients underwent surgeries whose volume included hysterectomy and, in most cases, systemic pelvic and/or paraaortic lymphadenectomy or biopsy of sentinel lymph nodes.

The surgical specimens obtained after the radical operation was investigated using standard histological and immunohistochemical methods of morphological examination. The following parameters were investigated: histological type of the uterine neoplasm (endometrioid, serous, clear cell, mixed); FIGO degree of tumor differentiation (grade): G1, G2, G3; depth of tumor invasion into myometrium (% of the total uterine wall thickness); invasion into the stroma of the cervix and presence of lymph-vascular invasion (LVI). Besides, the status of regional lymph nodes was assessed. For seventeen (17) patients, additional immunohistochemical, molecular and genetic examination of surgical specimens was performed to find POLE-mutations, identify markers of the mismatch repair system (MMR): MLH1, PMS2, MSH2, MSH6, expression of the p53 protein, estrogen (ER) and progesterone (PR) receptors. Based on these data, the molecular subtype of the tumor was identified: POLE-mutated (not found in this study), dMMR/MSI-H (repair deficit), p53abn (abnormal expression of p53), NSMP (non-specific ER-positive molecular profile), NSMP (non-specific ER-negative molecular profile).

Statistical processing of data. All statistical analyses were performed using R software (version 4.3.1) and Python (SciPy, Statsmodels, scikit-learn, seaborn libraries). The level of statistical significance was set at p < 0.05. For quantitative variables with a distribution that deviated from normal (assessed by the Shapiro–Wilk test), data are presented as medians and quartiles (Q1–Q3). Categorical variables are expressed as absolute and relative frequencies. For comparisons between two independent groups, the Mann–Whitney U test was used; for three or more groups, the Kruskal–Wallis test followed by Dunn's post hoc test was applied. The strength and direction of associations between quantitative/ordinal variables were evaluated using Spearman's rank correlation coefficient (ρ).

RESULTS

The complex statistical analysis of 34 patients with EC revealed sustainable statistically significant patterns of correlation between the PET/Ct metabolic parameters and key histopathologic characteristics of the tumors.

The most marked and statistically significant correlation was found between the value of [¹⁸F]FDG uptake intensity in the primary lesion (SUV max) and the tumor malignity degree (Grade). Spearman's rank correlation coefficient was ρ = 0.68 (p < 0.001), indicating a strong positive correlation. The analysis of distribution of SUVmax value across groups revealed a clear shift of metabolic parameters towards higher values as the differentiation decreased (Fig. 1). Median SUVmax for highly differentiated (Grade 1) tumors was 7.25 (6.10–8.95), for moderately differentiated (Grade 2), 7.2 (6.00–9.05) (p = 0.854), while for the poorly differentiated tumors (Grade 3) the value was significantly higher: 12.80 (10.40–15.70) (p < 0.01). Critically important is the result of the post hoc analysis that showed that the statistically significant differences (p < 0.01) exist exactly between the cumulative low-grade (Grade 1-2) group and the high-grade (Grade 3) group, while within the low-grade group the differences between Grade 1 and Grade 2 were not significant (p = 0.854). This allows regarding SUVmaxm in the first place, as the indicator discriminating between fundamentally different biological categories of tumors.

Figure 1. The distribution of the SUVmax index by the degree of tumor malignancy (Grade).

Рисунок 1. Распределение показателя SUVmax по степени злокачественности опухоли (Grade).

A statistically significant moderate positive correlation between the SUVmax value and depth of invasion into myometrium was found (ρ = 0.58, p = 0.001). In the comparison of groups of patients with superficial invasion (pT1a, ≤ 50% of myometrium thickness) and deep invasion (> pT1a, > 50%), median SUVmax in the latter group was reliably higher: 8.66 (7.10–11.20) vs. 6.40 (5.50–7.80); p = 0.012. This pattern confirms the hypothesis of tumors with elevated glycolysis having greater local invasion potential.

The analysis found a significant connection of SUVmax values with other adverse prognostic signs. Tumors of non-endometrioid histological types (serous, clear cell, mixed) manifested higher SUVmax values vs. typical endometrioid adenocarcinomas: median 11.02 (9.40–14.10) vs. 7.45 (6.20–9.00); p = 0.038). The highest SUVmax values, 13.33 and 16.86 were found in patients with aggressive histological types: Grade 3 mixed endometrioid and serous adenocarcinoma, Grade 3 endometrioid carcinoma with dMMR and metastatic lesions (Fig. 2). In the patient with a clear serous carcinoma (associated with p53 mutation), the SUVmax was only 7.5, at the same time, there were found multiple metastases to regional lymph nodes.

Figure 2. A combined PET/CT image in the coronal plane shows a metabolically active formation emanating from the posterior wall of the uterine body with high metabolic activity (white arrow). Physiological accumulation of RP in the right ureter and bladder (yellow arrows). Histological examination revealed a serous carcinoma of the uterine body with lesions of the right appendages. SUVmax = 9.95, MTV = 13.73, TLG = 81.6.

Рисунок 2. На совмещенном ПЭТ/КТ изображении в корональной плоскости определяется метаболически активное образование, исходящее из задней стенки тела матки с высокой метаболической активностью (белая стрелка). Физиологическое накопление РФЛП в правом мочеточнике и мочевом пузыре (желтые стрелки). При гистологическом исследовании обнаружена серозная карцинома тела матки с поражением правых придатков. SUVmax = 9,95, MTV = 13,73, TLG = 81,6.

The presence of lymph-vascular invasion (LVI), a key predictor of lymphatic metastatic spread, was also associated with a considerable increase of metabolic activity (median SUVmax 11.10 (9.20–13.80) in the presence of LVI vs. 7.22 (6.00–9.10)). Differences of SUVmax depending on the involvement of the cervical stroma (p = 0.084) and histologically confirmed metastasis to lymph nodes (p = 0.092) were observed as a trend but did not reach the level of statistical significance, which is likely related to the lower number of events in these subgroups. The metabolic activity in lymph nodes is a highly specific sign of their involvement, but the negative result on the PET does not exclude presence of micro-metastases (Fig. 3).

Figure 3. A combined PET/CT image in the axial plane in the left parts of the uterine body shows a metabolically active formation with high glycolytic activity (yellow arrow). Single non-exaggerated metabolically active pelvic lymph nodes are visualized (light green arrow. SUVmax = 2.08; SUVmax = 1.67). Physiological accumulation of RP in the colon (yellow arrows). Morphological examination revealed endometrioid adenocarcinoma of the uterine body, and regional lymph nodes contain structures of endometrioid adenocarcinoma. SUVmax = 5.59, MTV = 26.77, TLG = 82.

Рисунок 3. На совмещенном ПЭТ/КТ изображении в аксиальной плоскости в левых отделах тела матки определяется метаболически активное образование с высокой гликолитической активностью (желтая стрелка). Визуализируются единичные неувеличенные метаболически активные тазовые лимфоузлы (светло-зеленая стрелка. SUVmax = 2,08; SUVmax = 1,67). Физиологическое накопление РФЛП в толстой кишке (желтые стрелки). При морфологическом исследовании диагностирована эндометриоидная аденокарцинома тела матки, регионарные лимфоузлы содержат структуры эндометриоидной аденокарциномы. SUVmax = 5,59, MTV = 26,77, TLG = 82.

The immunobiological subtype of the endometrial cancer dMMR (MSI-H) was found in three patients. The SUVmax values in this group varied broadly from 6.4 to 16.86, which shows the heterogeneity of the dMMR group, and the metabolic characteristics of the tumor likely being more dependent on the concomitant factors (Grade, staging), than on the MMR status itself.

The data analysis of the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) revealed an expected strong correlation between these two parameters (ρ = 0.91). Both indicators continued the general trend demonstrating the higher values in the Grade 3 group and in the presence of LVI (Fig. 4). Median TLG of Grade 3 tumors (176.9) was several times higher than that of Grade 1-2 (37.6–38.5) regardless of the metabolic tumor volume.

Figure 4. Relationship of average values of MTV and TLG with the degree of tumor differentiation (Grade).

Рисунок 4. Взаимосвязь средних значений MTV и TLG со степенью дифференцировки опухоли (Grade).

DISCUSSION

This study, based on the analysis of 34 cases of EC, presents convincing statistical proof of a significant correlation between the quantitative indicators of PET/CT reflecting glycolytic activity of tumor tissue and fundamental prognostic factors of the disease with a statistically significant strong correlation (ρ = 0.68, p < 0.001). Critically important is the fact that the significant differences are observed between the low-grade (G1-2) and high-grade (G3) tumor groups, while he differences within the low-grade group itself (G1 vs. G2) were not significant. This agrees with the biological 'behavior' of the tumor: the transition to a poorly differentiated phenotype comes with a qualitative leap of metabolic activity.

Moderate correlation of SUVmax with depth of invasion (ρ = 0.58) and the reliable difference between the pT1a and > pT1a groups confirms that endometrial cancer characterized with a high glycolytic activity also has a higher invasion potential. Thus, the SUVmax index may be regarded as a useful tool for non-invasive evaluation of risk of deep invasion.

Statistically significant differences in SUVmax between the groups with and without LVI, as well as between endometrioid and other histological types emphasize the role of PET/CT in the identification of tumors with especially adverse biological behavior.

The obtained data aligns with findings of other studies. Thus, Y. Yang et al. (2023) also demonstrated a significant connection of SUVmax and TLG with the high degree of malignity (Grade 3) and depth of myometrial invasion [6]. S. Pacella et al. (2024) showed that threshold values of SUVmax make it possible to segregate low and high risk groups [8]. In the Russian literature, there are a few papers confirming the role of PET/CT in the evaluation of aggressiveness of endometrial cancer, however, the majority of them is limited to small cohorts. Our study augments these data with a detailed analysis not only of the SUVmax, but also volumetric indices MTV and TLG, as well as their connection with LVI and non-endometrioid histological types. At the same time, unlike С. Bezzi et al. (2013) [11], we did not find a statistically significant correlation of metabolic parameters with the status of regional lymph nodes, which might depend on the low number of patients with histologically confirmed metastases.

An interesting finding is the variability of SUVmax within molecular subtypes. While the NSMP subtype demonstrated to foreseeably low values of this index, the dMMR subtype demonstrated its wide range.

CONCLUSION

Thus, quantitative metabolic characteristics of the primary lesion using [¹⁸F]FDG PET/CT data in the endometrial cancer reflect the biological 'behavior' of the tumor. The obtained data support the integration of quantitative assessment of the maximum standardized uptake value of [¹⁸F]FDG and the total glycolytic index into preoperative workup algorithms to improve risk stratification, surgical planning, and adjuvant therapy decisions within the framework of personalized medicine [11–13].

ADDITIONAL INFORMATION	ДОПОЛНИТЕЛЬНАЯ ИНФОРМАЦИЯ
*Ethics approval.* The study was conducted in accordance with the ethical standards of the Helsinki Declaration. Approved by the Ethics Committee of the Almazov Center (extract from the minutes of the Ethics Committee meeting No. 1001-24 dated January 29, 2024).	*Этическая экспертиза.* Исследование выполнено в соответствии с этическими стандартами Хельсинкской декларации. Одобрено этическим комитетом Центра Алмазова (выписка из протокола заседания ЛЭК Nº1001-24 от 29.01.2024).
*Study funding.* The study was the authors' initiative without external funding.	*Источник финансирования.* Работа выполнена по инициативе авторов без привлечения финансирования.
*Conflict of interest.* The authors declare that there are no obvious or potential conflicts of interest associated with the content of this article.	*Конфликт интересов.* Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи.
*Contribution of individual authors.* Komlichenko E.E., Lanskaya E.V.: data collection, analysis and interpretation, writing of the text. Komlichenko E.V., Dikareva E.L., Ulrikh E.A.: general guidance, editing of the text, performance of the surgical stage. Koshevaya E.G., Raskin G.A., Mitrofanova L.B.: performing histological studies, editing of the text. Ryzhkova D.V.: general guidance, performing PET/CT studies, editing of the text. All authors gave their final approval of the manuscript for submission, and agreed to be accountable for all aspects of the work, implying proper study and resolution of issues related to the accuracy or integrity of any part of the work.	*Участие авторов.* Комличенко Э.Э., Ланская Е.В.: сбор, анализ и интерпретация данных, написание текста. Комличенко Э.В., Дикарева Е.Л., Ульрих Е.А.: общее руководство, редактирование текста, проведение хирургического этапа. Кошевая Е.Г., Раскин Г.А., Митрофанова Л.Б.: выполнение гистологических исследований, редактирование текста. Рыжкова Д.В.: общее руководство, выполнение ПЭТ/КТ исследований, редактирование текста. Все авторы одобрили финальную версию статьи перед публикацией, выразили согласие нести ответственность за все аспекты работы, подразумевающую надлежащее изучение и решение вопросов, связанных с точностью или добросовестностью любой части работы.
*Statement of originality.* No previously published material (text, images, or data) was used in this work.	*Оригинальность.* При создании настоящей работы авторы не использовали ранее опубликованные сведения (текст, иллюстрации, данные).
*Data availability statement.* The editorial policy regarding data sharing does not apply to this work.	*Доступ к данным.* Редакционная политика в отношении совместного использования данных к настоящей работе не применима.
*Generative AI.* No generative artificial intelligence technologies were used to prepare this article.	*Генеративный искусственный интеллект.* При создании настоящей статьи технологии генеративного искусственного интеллекта не использовали.
*Provenance and peer review.* This paper was submitted unsolicited and reviewed following the standard procedure. The peer review process involved 4 external reviewers.	*Рассмотрение и рецензирование.* Настоящая работа подана в журнал в инициативном порядке и рассмотрена по обычной процедуре. В рецензировании участвовали 4 внешних рецензента.

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