Demographics and patient treatment

A total of 205 patients with endometrial cancer were enrolled in the current study between January 2018 to December 2021. All patients were treated according to the NCCN guidelines for endometrial cancer. The patients’ demographic characteristics are shown in Table 1. Mean (range) follow-up time for survivors was 51.05 ± 5.00 (23–61) months and date of last follow-up was June 2023. The mean age was 58 years (35–87 years), and the mean BMI was 24.69 kg/m2 (range, 18.20–30.00 kg/m2). According to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria, 4 additional IVB patients underwent diagnostic curettage due to widespread liver, lung and bone metastasis. The histological diagnoses of these four patients were based on uterine biopsies and recorded FIGO stage on findings from diagnostic imaging. Apart from 6 IVA patients, including 5 with bladder mucosa metastasis, 2 patients with bowel mucosa metastasis underwent TH/BSO, and the remaining 195 (95.12%) patients underwent primary surgical resection with TH/BSO plus sentinel/pelvic/para-aortic lymphadenectomy. Regarding the surgical approach, a total of 185 patients (90.24%) underwent minimally invasive surgery—laparoscopy in 73.66% (151/205) and robotic in 16.59% (34/205)—and 16 patients (7.80%) underwent open surgery. Retroperitoneal para-aortic lymph node dissection was performed either via a laparoscopic approach and robotics platform or open surgery. Adjuvant therapy was given in 50.73% (104/205) of the patients, including radiation in 50.73% (104/205), chemotherapy in 40.98% (84/205), and hormonal treatment in 5.85% (12/205) of the patients.

Table 1 Patient characteristics and surgicopathological findings in 205 endometrial cancer patientsSurgico-pathological features

On final pathology, 105 patients (49.75%) were diagnosed with early stage IA, and the remaining 100 patients were diagnosed with stage IB, 21 (10.24%) and higher: stage II: 13 (6.34%), stage III: 59 (28.78%), and stage IV: 10 (4.88%). LVSI was depicted in 36.59% of patients (75/205). The percentages of tumor differentiation divided into grade 1, 2, and 3 tumors were 43.90% (90/205), 25.37% (52/205), and 30.73% (63/205), respectively. The most common histological type was endometrioid (172, 88.78%), followed by serous (15/205, 7.32%) and clear cell carcinoma (8/205, 3.90%). MI was detected in 29.76% (61/205) or 33.66% (69/205) of patients. ESI was observed in 12.68% (26/205) of patients. Pelvic lymph node dissection (PLND) was performed in 131 patients (95%, 131/205) and revealed LNM in 49.62% (65/131) of the patients, while paraaortic lymph node dissection (PALND) was conducted in 39 patients (19.02%) and revealed paraaortic LNM in 17.95% (7/39). Another 25 patients (12.20%) underwent sentinel lymphadenectomy (SLN). (Table 1).

Re-categorized according to 2023 FIGO staging

In 2023, the new FIGO staging system incorporates comprehensive clinical, surgical, histopathological, TNM (Tumor, Lymph Node, Metastasis), prognostic high-risk factors, and molecular subtyping for staging EC [21]. We re-categorized patient previously staged according to the 2009 FIGO system according to 2023 FIGO staging system. Since 2023 FIGO EC Staging, non-aggressive histological types are only composed of low-grade (grade 1 and 2) EECs, other types like high-grade EECs (grade 3), serous or clear cell were all defined as aggressive histological types. Furthermore, LVSI were also distinguished with no/focal or extensive/substantial. Thus, the adjustment of the EC Staging from 2009 to 2023 were: IA-IA1(N = 48), IA-IA2 (N = 42), IA-IC (N = 2), IA-IIB (N = 3), IA-IIC (N = 6), IB-IIC (N = 11). (Table 1) (Supplementary Table 1).

OS and DFS

Kaplan-Meier estimated 4-year OS (HR) for Stage IA, IB, II, III and IV according to 2009 FIGO was 98.00% (0.22), 95.20% (0.04), 83.90% (0.18), 90.50% (0.09) and 60% (0.51). Accordingly, estimated 4-year DFS (HR) for the stage IA-III was 98% (0.02), 95.20% (0.05), 76.90% (0.27) and 76.30% (0.35), all the patients in stage IV occurred recurrence and progression (Fig. 1).

Fig. 1

OS and DFS according to 2009 EC FIGO Staging. (A) Cumulative survival analysis of OS; (B) Cumulative Risk of HR for OS; (C) Cumulative survival analysis of PFS; (D) Cumulative Risk of HR for PFS.

Association between PET/CT Tumor parameters and surgico-pathological features

Upon comprehensive PET/CT analysis of and review of the 205 patients’ histopathological results, 83 patients (40.49%) had LNM, 28 patients (13.66%) had ESI, and 122 patients (59.51%) had MI, among SMI was detected in 32.20% (66/205) and 27.32% (56/205) of patients. There was a significant difference between DMI, ESI and pelvic LNM and SUVmax, SUVmean, MTV and TLG (P < 0.01). Additionally, a significant association between SUVmax vs. MTV and SUVmax vs. TLG in DMI (R = 0.2896, P = 0.0304; R = 0.4611, P = 0.0003), ESI (R = 0.4441, P < 0.0001, R = 0.4793, P < 0.0001) and LNM (R = 0.6352, P < 0.0001, R = 0.7734, P < 0.0001) was observed (Table 2).

Table 2 Parameters of diagnostic performance on a per-patient basisDifference of metabolic parameters in PET/CT between EC and EAH patients

Next, we compared metabolic parameters in PET/CT between EC and EAH patients’ myometrium, SUVmax (7.04 vs. 1.81), SUVmean (3.32 vs. 1.22), MTV (27.74 vs. 14.67), TLG (106.60 vs. 17.92), endocervical stroma: SUVmax (4.04 vs. 1.29), SUVmean (2.07 vs. 0.77), MTV (16.29 vs. 11.52), TLG (47.01 vs. 8.88), and lymph node SUVmax (4.85 vs. 1.06), SUVmean (2.68 vs. 0.72), MTV (23.22 vs. 6.95), TLG (77.03 vs. 5.05). There was a significant difference in metabolic parameters in PET/CT on myometrium, endocervical stroma and lymph node between EC and EAH patients (P < 0.01) (Table 3).

Table 3 Difference in metabolic parameters in PET/CT on myometrium, endocervical stroma and lymph node between EC and EAH patientsPrediction of myometrial and endocervical stromal invasion and regional lymph node metastasis by preoperative imaging parametersMI detection

The mean SUVmax and SUVmean of MI patients were significantly higher than those of patients who did not have MI (SUVmax value 10.75 vs. 1.58, SUVmean value 4.59 vs. 1.46, P < 0.01). The mean SUVmax and SUVmean of DMI patients were significantly higher than SMI patients (SUVmax value 11.29 vs. 10.29, SUVmean value 5.20 vs. 4.08, P < 0.01). The mean MTV and TLG values of patients who had myometrial invasion and did not have invasion were 34.68 vs. 17.55 ml and 161.60 vs. 25.71 g, respectively. The MTV and TLG cutoff values for MI were calculated to be 25.51 ml and 70.74 g, respectively, with a sensitivity and specificity yield of 100% (AUC = 1, P < 0.01). The mean MTV and TLG values of patients who had SMI and DMI 50% were 31.73 vs. 38.15 ml and 199.30 vs. 129.60 g, respectively. ROC curve analysis calculated an MTV cutoff value of 19.6 ml for identifying SMI and DMI (AUC = 0.8643, sensitivity = 43.94%, specificity = 100%, 95% CI 0.8025–0.9261, P < 0.01). The TLG cutoff value was 126.3 g for SMI and DMI (AUC = 0.9099, sensitivity = 45.45%, specificity = 100%, 95% CI 0.8605–0.9593, P < 0.01) (Fig. 2) (Table 4) (Supplementary Table 2).

Fig. 2

Lymph node metastasis (LNM) positivity and negativity calculated by PET/CT based on ROC curve analysis in 205 patients with endometrial cancer (A). MTV (B). TLG, myometrial invasion ≥ 50% and < 50% (C). MTV, (D). TLG, cervical interstitial invasion (E). MTV, (F). Best cutoff point of TLG; ordinate, sensitivity, abscissa, specificity;

Table 4 18 F-FDG PET/CT tumor markers in relation to surgical and histological tumor characteristics in 205 endometrial cancer patients

PET/CT understaged MI in 8 patients and DMI in 13 patients, and it over-staged SMI in 5 patients. Parameters of diagnostic performance including true positive (TP), true negative (TN), false-positive (FP), false negative (FN), sensitivity [(TP/TP + FN)*100%], specificity [(TN/FP + TN)*100%], accuracy [(TP + TN)/N*100%], positive predictive value (PPV) [(TP/TP + FP)*100%], and negative predictive value (NPV) [(TN/FN + TN)*100%] of PET/CT on a per-patient basis are shown in Table 4. The sensitivity of PET/CT to detect MI was 93.85%, and the specificity was 100%, with an accuracy of 96.10% with a PPV of 100% and an NPV of 90.36%. The sensitivity of PET/CT to detect SMI and DMI was 100% vs. 81.16%, and the specificity was 96.53% vs. 100%, accuracy 97.56% vs. 93.66%. The PPV and NPV were 92.42% vs. 100% and 100% vs. 91.28%, respectively (Fig. 2) (Table 4) (Supplementary Table 2).

Endocervical stroma invasion (ESI)

The mean SUVmax and SUVmean in patients who had ESI were significantly higher than those in patients who did not (SUVmax value 17.38 vs. 1.92, SUVmean value 6.12 vs. 1.43, P < 0.01). The mean MTV and TLG of patients who had ESI and did not have ESI were 36.28 vs. 13.13 ml and 225.10 vs. 18.84, respectively (P < 0.01). Using MTV cutoff values for predicting ESI, MTV > 20.54 ml yielded significantly higher specificity (100%) and specificity (92.86%). The TLG cutoff value was 84.80 g for ESI (AUC = 0.9895, sensitivity = 100.00%, specificity = 96.43%, 95% CI 0.9690-1.000, P < 0.01). PET/CT over-staged ESI in 2 patients. The sensitivity of PET/CT to detect ESI was 100%, the specificity was 98.89%, and the accuracy was 99.02%. The PPV and NPV were 92.85% and 100.0%, respectively (Fig. 2) (Table 4) (Supplementary Table 2).

Pelvic lymph node Metastasis (LNM)

For patients with negative and positive pelvic lymph nodes, the SUVmax and SUVmean were 1.72/1.44 vs. 9.47/4.49, respectively, and the mean MTV was 16.03 and 33.79, respectively. MTV yielded a cutoff value for pelvic lymph node positivity of 24 ml (AUC = 0.9705, sensitivity = 100%, specificity = 92.77%, 95% CI 0.9421–0.9989, P < 0.01). TLG was 23.02 and 156.40 between patients with negative and positive pelvic lymph nodes, respectively, and the TLG cutoff value was 49.38 g for lymph node positivity (AUC = 0.9642, sensitivity = 100.00%, specificity = 93.98%, 95% CI 0.9294–0.9989, P < 0.01). PET/CT over-staged the pelvic LNM in 18 patients. The sensitivity of PET/CT to detect pelvic LNM was 100%, the specificity was 87.14%, and the accuracy was 91.22%. The PPV and NPV were 78.31% and 100.0%, respectively (Figs. 2 and 3) (Table 4) (Supplementary Table 2).

Fig. 3

Survival of OS and DFS in MTV of MI and LNM.

OS in MTV of PET/CT; (B). DFS in MTV of PET/CT; (C). OS of PET- positive LN with MTV; (D). DFS of PET- positive LN with MTV.

Prediction of progression-free survival by preoperative imaging parameters

Patient follow-up was performed according to clinical examinations quarterly during the first 2 years and biannually until 5 years after primary diagnosis. The mean (range) follow-up time for survivors was 33 (20–44) months, and the date of last follow-up was 16 August 2021. In total, 14 out of the 205 (6.83%) patients experienced progression among patients primary staged as FIGO III–IV according to disease assessment adopts (Response Evaluation Criteria in Solid Tumor, RECIST, version 1.1). In total, 23 out of the 205 (11.22%) patients experienced progression, Among these patients’ metastatic lesions: bladder mucosa (n = 11), bowel mucosa (n = 4) 3, pelvic lymph nodes (n = 2), para-aortic lymph nodes (n = 3), liver (n = 1), lung (n = 7), bone (n = 3). (Table 1). A total of 5 patients suffered myocardial infarction and 2 died of pulmonary embolism. There was a relationship between cutoff of MTV and survival. When adjusting for preoperative high-risk status of MI, Patients with MTV > = 19.6 ml tended to predict poor OS and PFS with univariate hazard ratios (HRs) of 1.312 (p = 0.3766) and 2.210 (p = 0.0758), PET- positive LN with MTV cutoff > = 24 ml remained significantly associated with decreased DFS (HR = 2.178, p = 0.0065), and decreased OS (HR = 2.309, p = 0.0588), respectively (Fig. 4) (Supplementary Table 2).

Fig. 4

PET/CT images of endometrial cancer including trans-axial CT, fused PET/CT images of the lower abdomen revealed that intense 18 F-FDG uptake in the uterine and ovary cavity. A., A 54-year-old female patient with histologically confirmed endometrial adenocarcinoma in FIGO IA Stage, intrauterine lesions SUVmax 5.5; B. A 47-year-old female patient with histologically confirmed endometrial adenocarcinoma in Stage IA, intrauterine lesions range 4.1 × 1.7 cm2 with SUVmax 8.3. C. A 47-year-old female patient with histologically confirmed endometrial adenocarcinoma in Stage II, lesions on right ovary is range 6.8 × 4.6 cm2 with SUVmax 18.9 and intrauterine lesions SUVmax 17.0. D. A 58-year-old female patient with histologically confirmed endometrial serous carcinoma, intrauterine lesions rang 2.8*2.0*4.9 cm 3 with SUVmax 15.5, along with endocervical stroma lesions diameter 2.3 cm and SUVmax 4.1