Abstract
Objective:
In epithelial ovarian cancer (EOC), 2-fluorine-18-fluoro-deoxy-glucose (2-[18F]-FDG)-positron emission tomography (PET) with computed tomography (CT) outperforms CT and magnetic resonance imaging (MRI) in metastasis detection.
The aim of this early interim study was to assess feasibility of the study workflow to evaluate accuracy of 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI compared to stand-alone modalities in primary EOC staging.
Methods:
The first seven consecutive EOC participants in the prospective PRODIGYN study (NCT05855941) were included. All underwent 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI at baseline and 6/7 at 3-month evaluation. Molecular imaging-based stage according to International Federation of Gynaecology and Obstetrics (miFIGO) with 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI was compared to conventional radiological FIGO stage (crFIGO) with CT and MRI, using histopathological FIGO (pFIGO) as reference. At 3 months, therapy response assessment was performed with RECIST 1.1 and PERCIST.
Results:
At baseline, lymph node metastases were found in 3/7 with both modalities, and distant metastases in 2/7 with 2[18F]-FDG-PET/CT and 1/7 with PET/MRI. miFIGO was higher than crFIGO in 2/7, lower in 2/7, and the same in 3/7. At the 3-month therapy response assessment, RECIST 1.1 showed complete response in all, and PERCIST in 5/6, with partial response in 1/6.
Conclusion:
The PRODIGYN study workflow appears feasible for accuracy assessment of 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI compared to stand-alone modalities in primary EOC staging. Early data indicate a possible added value of 2[18F]-FDG-PET/CT and 2[18F]-PET/MRI.
Keywords: computed tomography, magnetic resonance imaging, neoplasm staging, ovarian cancer, positron emission tomography
Introduction
Ovarian cancer is the second most fatal gynecological malignancy worldwide[1]. Epithelial ovarian cancer (EOC) accounts for approximately 90% of all malignant ovarian neoplasms[2–4]. Due to late onset of symptoms, two-thirds of EOCs are diagnosed in advanced stages[5,6]. EOC staging is usually performed according to the 2021 revised International Federation of Gynaecology and Obstetrics (FIGO) staging system, or the tumor, node, metastasis (TNM) classification, both with the purpose of stratification of patients into different prognostic groups[4,7,8].
The rationale for accurate staging is ultimately to improve survival, by optimizing individualized treatment selection, where precise imaging can identify patients who might benefit from novel therapies or maintenance strategies[9].
HIGHLIGHTS
In epithelial ovarian cancer (EOC), 2-fluorine-18-fluoro-deoxy-glucose (2[18F]-FDG)-positron emission tomography (PET) with computed tomography (CT) outperforms CT and magnetic resonance imaging (MRI) in metastasis detection.
2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI are not currently recommended in primary EOC staging due to limited evidence.
Our preliminary data support that our study workflow is feasible for assessing the added value of 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI compared to stand-alone modalities for detection of distant metastases in primary staging of EOC.
Cross-sectional medical imaging has led to the inclusion of imaging findings into the FIGO staging system[10]. Magnetic resonance imaging (MRI) is used for evaluation of local tumor extension, while computed tomography (CT) and 2-fluorine-18-fluoro-deoxy-glucose (2[18F]-FDG) positron emission tomography with CT (PET/CT) are useful for metastasis assessment[11]. To date, European consensus recommendations do not support 2[18F]-FDG-PET/CT in primary staging of EOC[12,13]; however, there is growing evidence of the benefits in metastasis assessment with 2[18F]-FDG-PET/CT compared to stand-alone modalities[5,14] and current consensus is that hybrid PET imaging may enhance staging and management of EOC[15].
Another promising emerging imaging modality for staging and post-treatment response evaluation of EOC is PET/MRI, which has shown higher sensitivity and specificity than 2[18F]-FDG-PET/CT and MRI[11,14–16]. The current application status of PET/MRI in EOC is however not yet established due to insufficient evidence and limited due to restricted access to PET/MRI facilities throughout Europe as well as globally.
Specific imaging biomarkers may be identified for diagnostic and prognostic prediction, such as PET parameters maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), functional tumor volume (FTV), and total lesion glycolysis (TLG)[11,14]. SUVmax may help differentiate benign ovarian tumors from malignant lesions[12,17]. 2[18F]-FDG-PET/CT has shown additional value to both transvaginal ultrasound for differentiation of benign and malignant ovarian lesions, and to CT for staging[18]. Different histological subtypes differ in SUVmax, with low FDG uptake especially in clear cell and mucinous subtypes of EOC[19]. TLG may act as a predictive imaging biomarker for EOC metastasis and may have benefits in planning and monitoring of treatment[9].
The MRI diffusion-weighted imaging (DWI) parameter with apparent diffusion coefficient (ADC) maps for characterization of mucinous carcinoma has been described in several studies[20–22]. An ADC cutoff value of 1382 has been suggested to predict low-grade serous carcinoma and mucinous carcinoma with a specificity and sensitivity of 100% and 66.7%, respectively[20]. ADC could potentially compensate for the low FDG uptake in the diagnosis of clear cell and mucinous subtypes of EOC[16].
Imaging-based oncological treatment response assessment can be systematically performed according to RECIST 1.1 (Response Criteria in Solid Tumours) criteria[23], or PERCIST (PET Response Criteria in Solid Tumours). Response assessment by PERCIST seems to correlate better with patient outcome than RECIST 1.1[24].
The main aim of this interim study was to investigate the feasibility of the study workflow to assess the added diagnostic value of molecular imaging-based FIGO (miFIGO) with 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI compared to conventional radiological FIGO (crFIGO) based on clinical status and stand-alone imaging modalities, using histopathological FIGO (pFIGO) as reference, in primary staging of EOC. A second aim was to investigate the feasibility of T stage comparison according to TNM 8 between PET/CT and PET/MRI. The authors declare that no artificial intelligence was used in the research, as stated by the TITAN Guideline Checklist 2025[25].
Material and methods
Study design
This prospective single-center observational cohort study on EOC is part of the larger clinical trial PRODIGYN. The PRODIGYN study was approved by the Swedish Ethical Review Authority (ethical approval number 2022-04207-01) and performed in line with the principles of the Declaration of Helsinki. Informed consent for participation and for publication of de-identified data presented on group level or as anonymized image data was obtained from all study participants.
Study population
All eligible patients referred to the gynecological-oncological department of Umeå University Hospital and fulfilling the EOC inclusion criteria were consecutively offered participation in the study after written informed consent.
EOC inclusion criteria were previously untreated strongly suspected primary EOC, minimum 18 years of age, and no current or previously treated malignancy within the last 10 years. Exclusion criteria were imaging findings that implied other origin of primary tumor than EOC, MRI-incompatible devices or patient unable to undergo MRI, or uni- or bilateral hip prosthesis. A diagnosis of EOC or cancer abdominis of Müllerian origin, confirmed by histopathology according to the WHO classification of female genital tumors[26], within 6 months after inclusion was mandatory for remaining in the study.
Clinical assessment and data collection, storage, and availability
Clinical evaluation was performed at baseline and 3 months after start of treatment, along with serial 2[18F]-FDG-PET/CT and PET/MRI scans. All research data were pseudonymized, collected and stored in an electronic case report form (eCRF) using Research Electronic Data Capture[27,28] tools hosted at the Department of Diagnostics and Intervention, Umeå University. The de-identified research data in this study are available upon reasonable request.
PET/CT and PET/MRI imaging protocols
Study participants underwent 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI at baseline and at therapy response evaluation after 3 months. The 2[18F]-FDG-PET/CT was performed with a GE Discovery MI PET/CT scanner (General Electric, Waukesha, WI, USA) according to clinical routine[13,17]. PET/CT scanning was performed 60 minutes post- intravenous (iv) injection of 2-[18F]-FDG at a dose of 3 megabecquerel (MBq)/kg. The PET/MRI was performed on a GE Signa 3 T PET/MRI scanner (General Electric, Waukesha, WI, USA) 120 minutes post-injection using the same 2-[18F]-FDG injection, and with iv contrast gadoteric acid 279.3 mg/ml (Dotarem Guerbet, Villepinte, France), 0.2 ml/kg body weight (maximum 20 ml). Further imaging protocol details can be found in a previous PRODIGYN publication[29].
The 2[18F]-FDG-PET/MRI was performed according to standard clinical MRI protocol for ovarian cancer with preparatory administration of 2 ml Buscopan 20 mg/ml and included T2W (sagittal, axial, coronal), T1W Dixon all (axial), DWI (b 100, 800, axial), Gd + T1W Dixon (axial, sagittal).
Imaging parameters and imaging interpretation
All PET/CT scans were evaluated by at least one radiology resident and one double licensed specialist in nuclear medicine and radiology, according to local clinical routine. The PET/MRI scans were evaluated by a double-licensed specialist in nuclear medicine and radiology, with >10 years´ experience from gynecological-oncological radiology.
Baseline imaging parameters miFIGO, TNM (8th edition), SUVmax, SUVmean, FTV, and TLG were reported for both PET/CT and PET/MRI using the GE Healthcare Advanced Workstation Server, within manually positioned region of interest search boxes with an isocontour threshold at 42% of SUVmax. The PET/CT and PET/MRI examinations were read in a sequential, non-blinded manner.
MRI parameters volume, delineation, contrast enhancement, diffusion restriction, ADC, and risk stratification score according to Ovarian-Adnexal Reporting and Data System Magnetic Resonance Imaging (O-RADS) MRI[30] were assessed.
At the 3-month evaluation, changes in imaging parameters were evaluated and response evaluation according to RECIST 1.1 and PERCIST[23,24] was performed.
Reference FIGO stage
crFIGO was based on clinical examination and conventional radiology (CT and MRI) and determined by a gynecological oncologist. For patients treated with primary surgery, the crFIGO was determined only after surgical histopathological confirmation (pFIGO). Histopathological, immunohistochemical, and molecular genetic analyses (BRCA mutations and homologous recombination deficiency (HRD), defined by genomic instability score) were conducted using the 2021 revised FIGO staging system and the WHO 2020 classification of female genital tumors to define histological subtype and pFIGO [7 25].
Statistical analysis
Differences in T stage with 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI were only descriptively reported, given the small sample size. For categorical imaging parameters, descriptive frequencies were reported, and for quantitative imaging parameters, means with standard deviation (SD) and medians with standard error (SE) were presented.
In the larger cohort, accuracy of 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI compared to stand-alone modalities with histopathology as reference will be analyzed, and the imaging parameters will be analyzed using the non-parametric 2-sided Wilcoxon signed ranks test for related samples, with a level of significance of P < 0.05.
Results
Patient recruitment
Between start of enrolment in May 2023 until this early interim analysis in 13 November 2024 study participants had been recruited, and 7 remained. A STARD flow chart of patient recruitment and reasons for early discontinuation of the study is illustrated in Figure 1.
Figure 1.
STARD inclusion flow chart of study participants.
Clinical assessment
The characteristics and clinical data of the first seven study participants are described in Table 1.
Table 1.
Participants characteristics and clinical data.
| Mean | Std. deviation | ||
|---|---|---|---|
| Age | (years) | 60.3 | 9.6 |
| Height | (cm) | 165.6 | 7.7 |
| BMI | 25.7 | 5.0 | |
| Menarche age | (years) | 12.8 | 2.5 |
| Menopause age | (years) | 50.7 | 3.3 |
| Parity | (n) | 2.0 | 0.8 |
| Frequency | Percent (%) | ||
| Smoking habits | Never smoked | 4/8 | 50 |
| Stopped smoking | 3/8 | 37.5 | |
| Active smoker | 1/8 | 12.5 | |
| Frequency | Percent (%) | ||
| Snuff use | Never | 6/8 | 75 |
| Sporadic | 2/8 | 25 | |
| Frequency | Percent (%) | ||
| Menstruating | No | 7/8 | 87.5 |
| Yes | 1/8 | 12.5 | |
| Frequency | Percent (%) | ||
| Reason for amenorrhea | Menopause | 6/8 | 75 |
| Hysterectomy | 1/8 | 12.5 | |
| Still menstruating | 1/8 | 12.5 | |
| Frequency | Percent (%) | ||
| cFIGO | FIGO I-IIIB | 4/8 | 50 |
| FIGO IIIC or >IIIC | 3/8 | 37.5 | |
| Total | 7 | 87.5 | |
| Missing | 1 | 12.5 | |
| cFIGO* | |||
| OVCA 3 = IIIA2 | |||
| OVCA 5 = IIA1 | |||
| OVCA 7 = IIIC | |||
| Frequency | Percent (%) | ||
| Treatment | No surgery performed | 1/8 | 12.5 |
| Primary surgery | 4/8 | 50 | |
| NACT + cytoreductive surgery | 3/8 | 37.5 | |
| Mean | Std. deviation | ||
| CA 19-9 (U/mL) | 23.1 | 26.0 | |
| CA 125 (U/mL) | 3377.9 | 7983.4 | |
| Frequency | Percent (%) | ||
| Histological subtype | High-grade serous carcinoma | 5/8 | 62.5 |
| Endometrioid carcinoma | 1/8 | 12.5 | |
| Mucinous carcinoma | 1/8 | 12.5 | |
| Missing | 1/8 | 12.5 | |
| Total | 8 | 100 |
Descriptive statistics: mean (standard deviation = SD) and frequencies (%) and number (n). BMI, body mass index; CA 125, cancer-associated antigen 125; CA 19-9, cancer-associated antigen 19-9; cFIGO, Clinical International Federation of Gynecology and Obstetrics stage; cFIGO*, cFIGO determined before surgical histopathological confirmation; NACT, neoadjuvant chemotherapy.
2[18F]-FDG-PET/MRI and 2[18F]-FDG-PET/CT for baseline N and M metastasis detection
Lymph node metastases were found in 3/7 with both modalities, and distant metastases in 2/7 with 2[18F]-FDG-PET/CT and 1/7 with 2[18F]-FDG-PET/MRI.
Comparison of T stage with 2[18F]-FDG-PET/MRI and 2[18F]-FDG-PET/CT
T stage was higher with [18F]-FDG-PET/CT compared to 2[18F]-FDG-PET/MRI in 2/7, and the same in 5/7. The use of 2[18F]-FDG-PET/MRI did not cause up-staging of T stage in any of the cases.
Comparison of miFIGO stage with 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI versus crFIGO and pFIGO
miFIGO stage was higher with 2[18F]-FDG-PET/CT compared to 2[18F]-FDG-PET/MRI in 4/7 participants, and the same in 3/7. None was upstaged with 2[18F]-FDG-PET/MRI. miFIGO was higher than crFIGO in 2/7 (both distant metastases, one verified by pFIGO, lower in 2/7 and the same in 3/7.
Therapy response assessment at 3 months
RECIST 1.1 showed complete response in all and PERCIST in 5/6, with partial response in 1/6.
Imaging parameters for each participant at baseline and 3-month follow-up are presented in Table 2.
Table 2.
Imaging parameters at baseline and 3-month follow-up.
| Baseline | Modality | Mean | SD | Median | SE | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study participants | OVCA 1 | OVCA 3 | OVCA 5 | OVCA 6 | OVCA 7 | OVCA 10 | OVCA 11 | OVCA 12 | ||||||
| FDG uptake assessment | PET/CT | 3 | 4 | 4 | 4 | 3 | 4 | 4 | 4 | |||||
| SUVmax | PET/CT | 14.4 | 25 | 31.7 | 10.7 | 6.6 | 10.2 | 14 | 17.6 | 16.3 | 8.3 | 14.2 | 2.9 | |
| SUVmean | PET/CT | 7.5 | 12.5 | 17.6 | 7.3 | 3.8 | 6.1 | 7.7 | 9.3 | 9 | 4.3 | 7.6 | 1.5 | |
| FTV | PET/CT | 32.6 | 44.2 | 18 | 2.2 | 3 | 8.2 | 10.1 | 136.6 | 31.9 | 44.8 | 14.1 | 15.9 | |
| TLG | PET/CT | 244.5 | 552.5 | 316.8 | 15.9 | 11.4 | 50 | 7.8 | 1270.5 | 317.4 | 428.0 | 161.2 | 151.3 | |
| Delineation | PET/CT | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | |||||
| Contrast enhancement | PET/CT | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
| rFIGO | PET/CT | IIIB | IIIB | I | IVA | IVA | IIIC | I | IVB | |||||
| O-RADS | PET/MRI | 5 | 5 | 4 | 5 | 1 | 5 | 4 | 5 | |||||
| SUVmax | PET/MRI | 14.5 | 24.2 | 29.1 | 8.6 | 4 | 7.9 | 10.5 | * | 14.1 | 9.2 | 10.5 | 3.5 | |
| SUVmean | PET/MRI | 7.8 | 12.4 | 16.2 | 5.8 | 2.4 | 4.7 | 5.7 | * | 7.9 | 4.8 | 5.8 | 1.8 | |
| FTV | PET/MRI | 45.1 | 57.7 | 16.2 | 3.7 | 4.2 | 10.8 | 14.1 | * | 21.7 | 21.1 | 14.1 | 8.0 | |
| TLG | PET/MRI | 351.8 | 715.5 | 408.2 | 21.5 | 10.1 | 50.8 | 80.4 | * | 234 | 267.2 | 80.4 | 101.0 | |
| Volume | PET/MRI | 1152 | 3536 | 1203 | 299 | 2.5 | 84.9 | 1293 | 1427 | 1 124.6 | 1 131.6 | 1 177.5 | 400.1 | |
| ADC | PET/MRI | 1200 | 875 | 1146 | ** | 1140 | 1044 | 1564 | 886 | 1 122.1 | 232.8 | 1 140 | 88.0 | |
| Diffusion restriction | PET/MRI | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
| rFIGO | PET/MRI | I | IIIB | I | IIIC | IIIC | I | I | ** | |||||
| Follow-up | ||||||||||||||
| FDG uptake assessment | PET/CT | 3 | 0 | ** | 0 | 0 | 0 | 0 | 0 | |||||
| PERCIST | PET/CT | PMR | CMR | CMR | ** | CMR | CMR | CMR | CMR | |||||
| RECIST | PET/CT | CR | CR | CR | ** | CR | CR | CR | CR | |||||
| SUVmax | PET/CT | 4.1 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| SUVmean | PET/CT | 2.2 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| FTV | PET/CT | 1.2 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| TLG | PET/CT | 2.6 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| rFIGO | 1 | 0 | 0 | ** | 0 | 0 | 0 | 0 | ||||||
| O-RADS | PET/MRI | 1 | 1 | 1 | ** | 1 | *** | *** | 1 | |||||
| SUVmax | PET/MRI | 0 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| SUVmean | PET/MRI | 0 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| FTV | PET/MRI | 0 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| TLG | PET/MRI | 0 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| Volume | PET/MRI | 0 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| ADC | PET/MRI | 0 | 0 | 0 | ** | 0 | 0 | 0 | *** | |||||
| rFIGO | PET/MRI | 0 | 0 | 0 | ** | 0 | 0 | 0 | 0 | |||||
| pFIGO | IIIB | IVB | I | IIIB | IVA | IIIC | I | **** |
SUV measurements in grams/mL, volume and FTV in cm 3, ADC in mm2/s.
ADC, apparent diffusion coefficient; BMI, body mass index; CA 125, cancer-associated antigen 125; CA 19-9, cancer-associated antigen 19-9; CMR, complete metabolic response; CR, complete response; CT, computed tomography; FDG, fluorine-fluoro-deoxy-D-glucose; FTV, functional tumor volume; MRI, magnetic resonance imaging; O-RADS, Ovarian-Adnexal Imaging Reporting and Data System; OVCA, ovarian cancer patients’ identification code within the Prodigyn study; pFIGO, histopathological International Federation of Gynecology and Obstetrics stage; PERCIST, Positron Emission Tomography Response Criteria in Solid Tumours; PET, positron emission tomography; PMR, partial metabolic response; RECIST, Response Evaluation Criteria in Solid Tumours; rFIGO, radiological International Federation of Gynecology and Obstetrics stage; SD, standard deviation; SE, standard error; SUVmax, maximum standardized uptake value; SUVmean, mean standardized uptake value; TLG, total lesion glycolysis; * = no value obtained. Technical error with attenuation correction. ** = adverse event – prematurely ending the radiological examination. *** = no reported data. **** = no surgery performed.
Figure 2 illustrates 2[18F]-FDG-PET/MRI and T2W MRI of a representative study participant.
Figure 2.
2[18F]-FDG-PET/MRI and T2W MRI of bilateral epithelial ovarian cancer. Axial views (a, b) and coronal views (c, d). Blue and green arrows indicate high 2[18F]-FDG uptake in solid portions of the bilateral ovarian tumors. Purple and orange arrows show corresponding hypointense areas in T2W images.
Histopathological assessment
Table 3 shows the distribution of histopathological subtypes, with immunohistochemical and genetic test results.
Table 3.
Histopathological, immunohistochemical, and genetic testing.
| OVCA | Histopathological subtypes | Ki-67 | HRD | Genomic instability score (%) | BRCA gene |
|---|---|---|---|---|---|
| 1 | HGSC | * | Positive | 63 | BRCA 2 |
| 3 | HGSC | * | Positive | 54 | Negative |
| 5 | EC | 57 | ** | ** | Negative |
| 6 | HGSC | * | Negative | 38 | Negative |
| 7 | HGSC | * | Positive | 78 | Negative |
| 10 | HGSC | * | Negative | 32 | Negative |
| 11 | MC | * | *** | * | *** |
BRCA, breast cancer-associated antigen; EC, endometrioid carcinoma; HGSC, high-grade serous carcinoma; HRD, homologous recombination deficiency; Ki-67, antigen Kiel 67; MC, mucinous carcinoma; OVCA, ovarian cancer patients’ identification code within the Prodigyn study.
One participant had no surgery and is therefore excluded from this table. 5/7 (71,4%) had HGSC subtype, 1/7 (14,3%) had EC as subtype and 1/7 (14,3%) had MC subtype. * = missing data. ** = inconclusive. *** = not performed.
Discussion
2[18F]-FDG-PET/MRI and 2[18F]-FDG-PET/CT for N and M metastasis detection
The results support that the PRODIGYN study workflow would be feasible for evaluation of accuracy of 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI compared to stand-alone modalities in primary EOC staging. Preliminary data from the first seven participants indicate that 2[18F]-FDG-PET/MRI and 2[18F]-FDG-PET/CT may possibly have an incremental value to stand-alone modalities in detection of N and M metastasis in primary staging of EOC, but due to the small sample size, the results must be interpreted with caution. A previous meta-analysis and review showed that the mean incidence of lymph node metastasis in clinically early EOC stages I and II was 14.2% and that the highest incidence of metastasis was found in the serous subtype[31], which is in line with our results.
The future findings of the completed study cohort will be of special clinical interest, since 2[18F]-FDG-PET/CT is not currently recommended for primary staging of EOC in national guidelines, due to limited evidence[12,13]. There is however an increasing amount of studies suggesting a benefit of 2[18F]-FDG-PET/CT in EOC staging for metastasis assessment, compared to stand-alone CT or MRI[5,14]. This is also supported by the known fact that the sensitivity and specificity of lymph node assessment in pelvic tumors with CT or MRI are only modest[32]. Given the frequently low 2[18F]-FDG avidity of mucinous and clear cell subtypes of EOC, PET/MRI may have a potential advantage particularly with regards to established parameters suggestive of malignancy, such as contrast enhancement, restricted DWI and low ADC values, as well as T1 characteristics suggestive of mucinous content, to improve diagnostic accuracy in these cases.
Comparison of T stage with 2[18F]-FDG-PET/MRI and 2[18F]-FDG-PET/CT
Contrary to our hypothesis, T stage was found higher with [18F]-FDG-PET/CT, and 2[18F]-FDG-PET/MRI did not cause up-staging in any of the cases in our small cohort. Both study participants with higher T stage with [18F]-FDG-PET/CT were miFIGO IIIB and IIIC, i.e. peritoneal tumor spread beyond the pelvis. This result cannot yet support any conclusions, but as expected emphasizes the need for a whole-body examination for metastasis assessment regardless of imaging modality, which is also supported by other studies[33].
Comparison of miFIGO stage with 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI versus crFIGO and pFIGO
The different fields of view between the modalities have most likely affected the preliminary result where miFIGO stage was found higher with 2[18F]-FDG-PET/CT. As discussed earlier, the extent of a T3 tumor may not be included in a smaller field of view, as with the PET/MRI protocol. In addition, the use of gadolinium contrast for MRI versus no contrast for CT impacts comparability. Furthermore, PET/CT and PET/MRI were performed sequentially with different uptake times (60 min post-injection for PET/CT versus 120 min for PET/MRI). These methodological differences introduce possible confounding factors that may influence SUVmax and SUVmean measurements and potentially affect the detection of lesions, particularly in a small cohort.
On patient basis, there was no difference regarding lymph node status between miFIGO and crFIGO. However, several studies have shown higher pooled sensitivity and specificity of 2[18F]-FDG-PET/CT than CT and MRI for detection of lymph node metastases[34,35].
Regarding peritoneal metastasis, some studies on gastrointestinal cancer indicate comparable performance of 2[18F]-FDG-PET/CT and DWI-MRI or even that DWI-MRI outperforms 2[18F]-FDG-PET/CT[36] and CT[37], but the applicability of these findings on EOC is unknown. Limited data suggests that whole-body- 2[18F]-FDG-PET/MRI can be useful in estimating total spread of carcinomatosis and concludes that the main clinical advantage of 2[18F]-FDG-PET/MRI seems to be in deciding operability in primary staging of EOC with high tumor burden[16].
The interesting result that miFIGO was higher than crFIGO in 2/7 may have clinical implications, where upstaging of EOC may impact treatment recommendations and options, and survival rates.
Our slightly divergent results on tumor response assessment with PERCIST and RECIST 1.1 support previous literature suggesting a difference between response assessment by metabolic PERCIST and anatomical RECIST 1.1[38]. Morphological measurements based on CT have limitations in tumors with obscure margins, cystic lesions, or scar tissue and concerns have been raised about assessing tumor response with RECIST 1.1 in patients receiving novel targeted agents. PERCIST however, can allow measurements of tumor response even in the absence of structural changes and appears to be a potential predictor of outcome, superior to RECIST 1.1[38].
There was a trend of higher SUVmax and SUVmean for 2[18F]-FDG-PET/CT compared to -PET/MRI. As suggested in some studies[39–42], lower SUVmean and SUVmax have been observed in malignant tumors in sequentially conducted PET/CT and PET/MRI, which may be explained by different sampling times after injection.
Strengths and limitations of the study
This early interim analysis has several inherent limitations. The study was designed as a single-center observational cohort study, with short follow-up time. The small sample size does not warrant any reliable statistical analysis, but this is rather to be seen as a methodological description of future analysis of the entire study cohort. The histopathological verification of suspected lymph node or distant metastases was incomplete, as not every lesion was subject to biopsy. However, it is not ethically justified to perform biopsy on each lesion. Instead, in each case with suspected lesions causing stage migration, these stage-determining lesions were verified by biopsy and thus this approach did not hamper the reliability of the miFIGO and crFIGO comparisons.
The different fields-of view, and the fact that gadolinium contrast was favored before iodine contrast, make comparison of imaging modalities less feasible. Furthermore, the sequential, non-blinded reading of examinations introduces potential bias. This approach was due to clinical requirements with clinical reports delivered within a stipulated time frame but will be adjusted in future study readings to improve robustness and reliability of the study design.
The strengths of the study involve the use of standardized clinical protocols according to European guidelines for clinical PET/CT and MRI, and the use of quantitative biomarkers which made the evaluation less subjective. Our small study population follows the normal distribution of EOC, where approximately 70% are diagnosed with advanced disease (III/IV), supporting that our results from the future intended larger cohort should be valid and transferable with high generalizability[43].
Conclusion
The PRODIGYN study workflow appears feasible for accuracy assessment of 2[18F]-FDG-PET/CT and 2[18F]-FDG-PET/MRI compared to stand-alone modalities in primary EOC staging. Early data indicate a possible added value of 2[18F]-FDG-PET/CT and 2[18F]-PET/MRI.
Acknowledgements
We thank research assistant Erika Figaro for her valuable assistance in patient recruitment and study inclusion.
Footnotes
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Published online 23 March 2026
Contributor Information
Karolina Rosendahl, Email: karo0040@student.umu.se.
Malin Båtsman, Email: malin.batsman@regionvasterbotten.se.
Ulrika Ottander, Email: ulrika.ottander@umu.se.
Sara N. Strandberg, Email: sara.strandberg@umu.se.
Ethical approval
The PRODIGYN study was approved by the Swedish Ethical Review Authority (ethical approval number 2022-04207-01) and performed in line with the principles of the Declaration of Helsinki.
Consent
Informed consent for participation and for publication of de-identified data presented on group level or as anonymized image data was obtained from all study participants.
Sources of funding
Financial support and sponsorship: Internal strategic funding, Department of Diagnostics and Intervention, Umeå University.
Author contributions
K.R.: visualization, investigation, writing- original draft preparation. M.B.: conceptualization, methodology, writing- reviewing and editing. U.O.: conceptualization, methodology, writing- reviewing and editing. S.N.S.: conceptualization, methodology, data curation, visualization, investigation, supervision, validation, writing- original draft preparation, reviewing and editing.
Conflicts of interest disclosure
The authors have no relevant financial or non-financial conflicts of interest to disclose.
Research registration unique identifying number (UIN)
Prognostic and Diagnostic Added Value of Medical Imaging in Gynaecological Cancer (PRODIGYN, NCT05855941, date of registration 2023-05-23) https://clinicaltrials.gov/study/NCT05855941
Guarantor
Sara Natasa Strandberg.
Provenance and peer review
Not commissioned, externally peer reviewed.
Data availability statement
Research data available upon reasonable request.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Research data available upon reasonable request.