Role of F-18 FDG PET/CT in Detecting Metastatic Disease during Initial Staging of Carcinoma Breast

Breast cancer remains the most prevalent malignancy and a leading cause of cancer-related mortality among women worldwide. According to the GLOBOCAN 2020 data, it accounts for more than 2.3 million new cases annually, representing nearly 11.7% of all cancers in women. The burden is disproportionately higher in developing countries where late-stage diagnosis predominates due to lack of screening awareness and limited diagnostic infrastructure. Early and accurate staging is thus crucial for appropriate management and improved survival outcomes.[1][2]

Conventional imaging modalities such as mammography, ultrasonography, and magnetic resonance imaging (MRI) primarily provide morphological details that help assess the local extent of disease. However, these methods have limited sensitivity in detecting occult nodal and distant metastases, which are critical determinants of prognosis and treatment planning. Functional imaging with Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (F-18 FDG PET/CT) has revolutionized oncologic imaging by combining metabolic and anatomic information in a single scan.[3][4]

The biologic basis of FDG-PET lies in the increased glycolytic rate of malignant cells due to overexpression of glucose transporter (GLUT-1, GLUT-3) and elevated hexokinase activity. The radiolabeled glucose analogue, FDG, is trapped intracellularly as FDG-6-phosphate, allowing visualization of hypermetabolic tumor tissue. PET/CT thus enables whole-body metabolic mapping, improving the detection of both locoregional and distant disease.[5]

Quantitative PET parameters-standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)-have emerged as potential biomarkers reflecting tumor aggressiveness and total metabolic burden.

SUVmax, the peak uptake within the region of interest, reflects the highest metabolic activity but does not consider tumor volume.

MTV quantifies the volume of metabolically active tumor tissue above a defined threshold.

TLG, derived as MTV × SUVmean, integrates both intensity and extent of FDG uptake, representing overall tumor glycolytic activity.

Aim

To quantitatively assess metabolic parameters (SUVmax, MTV, and TLG) on F-18 FDG PET/CT in breast cancer staging and evaluate their correlation with disease extent.

Objectives

1.             To determine the metabolic parameters (SUVmax, MTV, TLG) of primary breast lesions and metastatic sites using F-18 FDG PET/CT.

2.             To compare these quantitative parameters between locally advanced breast cancer (LABC) and non-LABC groups.

3.             To analyze the role of PET-derived metabolic parameters in disease upstaging and their potential prognostic significance.

Table 1: Cohort overview & correlation with disease extent at baseline (N = 88)

The study cohort comprised 88 female patients with biopsy-proven breast carcinoma, of which 73 (83%) were classified as non-locally advanced breast cancer (non-LABC) and 15 (17%) as LABC. The mean age of participants was 52.68 ± 11.74 years, with most lesions occurring in the left breast (67%). Lymph node involvement was common, identified in 80.7% of cases. Distant metastases at baseline were detected in 39.8% overall, occurring more frequently among non-LABC cases (43.8%) compared to LABC (20.0%), though this difference did not reach statistical significance (χ² = 2.9, p = 0.086).

Quantitative PET parameters demonstrated higher metabolic activity in LABC compared to non-LABC. The mean primary tumor SUVmax was 27.67 ± 4.23 in LABC and 22.31 ± 5.69 in non-LABC, showing a borderline difference (p = 0.071, 95% CI -11.25 to 0.54). Similarly, the total metabolic tumor volume (MTV) was higher in LABC (401.68 ± 72.41 mL) versus non-LABC (226.99 ± 176.85 mL; p = 0.094). The total lesion glycolysis (TLG) showed a statistically significant increase in LABC (p = 0.041, 95% CI -340.70 to -8.69), indicating a greater total metabolic burden.

Table 2: PET-derived metabolic parameters for primary lesions and metastatic sites (N = 88)

Quantitative analysis of PET/CT parameters revealed distinct metabolic profiles between primary lesions and metastatic sites. The mean SUVmax of primary breast lesions was 19.90 ± 10.40, whereas regional lymph nodes had a lower mean SUVmax of 14.22 ± 9.50, reflecting the gradient of metabolic intensity from the primary tumor to metastatic nodes. Mean SUV values followed a similar trend (12.22 ± 5.78 in primary vs 8.97 ± 6.10 in nodes).

The mean MTV for primary lesions was 37.00 ± 64.10 mL, while the MTV of nodal disease averaged 76.68 ± 500.51 mL. The total MTV for all lesions combined was 99.60 ± 483.34 mL. Likewise, total lesion glycolysis (TLG) was markedly higher in primary tumors (55,287.87 ± 462,329 a.u.) compared to regional nodes (187.90 ± 802.30 a.u.), with an overall total TLG of 3,097.45 ± 20,887 a.u.

Table 3: Comparison of quantitative parameters between LABC and non-LABC

When comparing metabolic indices between LABC and non-LABC patients, a consistent trend toward higher metabolic activity was observed in LABC. The mean SUVmax of the primary tumor was greater in LABC (27.67 ± 4.23) than in non-LABC (22.31 ± 5.69), although the difference did not reach conventional statistical significance (p = 0.071). The mean total MTV was also higher among LABC patients (401.68 ± 72.41 mL) compared to non-LABC cases (226.99 ± 176.85 mL; p = 0.094). The total lesion glycolysis (TLG), however, showed a statistically significant increase in LABC (p = 0.041, 95% CI -340.70 to -8.69), signifying a greater tumor burden and metabolic aggressiveness.

Table 4: Upstaging analysis and prognostic metabolic markers

Upstaging analysis using PET/CT demonstrated that the mean SUVmax did not significantly differ between LABC (19.67 ± 7.45) and non-LABC (19.55 ± 7.43) groups (p = 0.962), indicating that baseline SUVmax alone was insufficient to predict upstaging. In contrast, both MTV and TLG showed highly significant differences between the two categories. Non-LABC patients who were upstaged on PET/CT exhibited markedly elevated MTV (124.64 ± 581.06 mL) and TLG (703.61 ± 2,022.20 a.u.) compared to LABC patients (MTV = 83.76 ± 94.11 mL; TLG = 1,457.50 ± 2,845.00 a.u.), with both comparisons yielding p < 0.0001 (Mann–Whitney U test). Survival analysis revealed a significant difference between groups: 87.7% of non-LABC patients survived compared to 66.7% in LABC (χ² = 4.10, p = 0.043).

Table 1, Cohort (N=88) is middle-aged (mean 52.7 years) with left-breast predominance (67%) and a high burden of nodal disease at baseline (80.7%). In Table 1, nearly two in five patients had distant metastasis at presentation (39.8%). Although the proportion with metastasis was numerically higher in non-LABC (43.8%) than LABC (20.0%), this difference did not reach conventional significance (p=0.086). Such a high overall metastatic yield at initial work-up aligns with reports from settings where late presentation is common and where FDG PET/CT is used early for whole-body staging; studies in LABC consistently show that PET/CT detects additional N3 or distant disease beyond conventional imaging and leads to upstaging in a substantial fraction of patients (often ~30–50%) Delgado Bolton RC et al. (2021)[6].

Quantitatively, LABC showed higher metabolic burden: primary SUVmax trended higher (27.7 vs 22.3; p=0.071) and total MTV was larger (402 vs 227 mL; p=0.094), with total TLG significantly higher in LABC (p=0.041). This pattern echoes the growing evidence that volume-integrated metrics (MTV/TLG) capture global tumor aggressiveness better than peak intensity (SUVmax). Multiple studies in operable and locally advanced breast cancer link higher baseline MTV/TLG to adverse pathology, higher recurrence risk, and poorer survival, frequently outperforming SUVmax for prognostication Turan U et al. (2021)[7]; Morariu DS et al. (2020)[8]. The non-significant p-values for SUVmax and MTV here likely reflect sample size and variance, but the consistent directionality (higher in LABC) supports their biological relevance.

Table 2 decomposes metabolism by site. Primary tumors exhibited higher intensity (SUVmax 19.9; SUVmean 12.2) than regional nodes (SUVmax 14.2; SUVmean 9.0), while nodal disease contributed substantially to the cumulative metabolic burden (total MTV ≈100 mL; total TLG ≈3,097 a.u.). This dichotomy-higher intensity at the primary, but meaningful volume in nodal/whole-body disease-underscores why TLG (MTV×SUVmean) is a powerful integrator. Prior work shows that nodal MTV and whole-body MTV/TLG correlate with pathologic stage and outcomes, sometimes more strongly than primary-tumor SUVmax alone Su TP et al. (2021)[9]. The lower mean nodal SUV but sizable MTV you observe is consistent with metastatic deposits being more diffuse or multifocal, contributing more “volume” than “peak” signal-precisely the scenario where TLG adds value.

Table 3 directly contrasts LABC vs non-LABC. The significant elevation of TLG in LABC (p=0.041) mirrors reports that TLG tracks composite tumor load and is associated with shorter disease-free survival (DFS) and overall survival (OS) in both neoadjuvant and surgery-first cohorts Bicakci N. (2022)[10]. The trend toward higher SUVmax in LABC is biologically plausible, but SUVmax alone is a single-voxel metric sensitive to noise, glycemia, and timing; meta-analytic evidence supports SUVmax as a risk marker but with heterogeneous effect sizes across subtypes and stages Kim K et al. (2021)[11]. Your data-borderline for SUVmax, significant for TLG-fit the consensus that volumetric metrics are more robust discriminators of advanced biology.

Table 4 examines upstaging and prognosis. Post-PET/CT “upstaged” cases showed no difference in SUVmax between non-LABC and LABC (p=0.962), but MTV and TLG were highly different (both p<0.0001), reinforcing that upstaging is predominantly a function of total metabolically active burden rather than peak intensity. This observation resonates with metastatic-cohort analyses where whole-body MTV/TLG (rather than SUVmax) stratified OS across sites (bone, node, liver) and in aggressive phenotypes such as triple-negative disease Mirshahvalad SA et al. (2024)[12]. Your survival table (87.7% alive in non-LABC vs 66.7% in LABC; p=0.043) is directionally concordant with these findings-patients with higher metabolic burden fare worse. Together, the four tables support a pragmatic hierarchy for PET-derived biomarkers in staging breast cancer: use SUVmax to flag biologic intensity, but rely on MTV/TLG to quantify disease extent, anticipate upstaging, and inform prognosis.

The present study demonstrates that quantitative metabolic parameters derived from F-18 FDG PET/CT-specifically SUVmax, MTV, and TLG-serve as valuable imaging biomarkers in the staging and prognostic evaluation of breast cancer. Among the parameters, volumetric indices (MTV and TLG) provided superior correlation with disease extent compared to SUVmax, underscoring their relevance in assessing total metabolic tumor burden rather than mere focal intensity. LABC cases consistently exhibited higher values for all three indices, with TLG showing statistically significant association with advanced disease stage (p = 0.041). Moreover, patients with higher total MTV and TLG were more likely to be upstaged on PET/CT and demonstrated poorer survival outcomes, highlighting their prognostic potential. These findings reaffirm that integrating metabolic quantification into routine PET/CT reporting can refine risk stratification, guide therapeutic planning, and predict patient outcomes more effectively than conventional anatomic staging alone.

Limitations Of the Study

This study had several limitations. First, the sample size (n = 88) was relatively small, potentially underpowering subgroup comparisons such as LABC versus non-LABC. Second, histopathological correlation and molecular subtype analysis (ER, PR, HER2, Ki-67) were not uniformly available, limiting biological validation of PET parameters. Third, although efforts were made to standardize imaging and reconstruction, inter-scanner variability, uptake time differences, and partial-volume effects may have introduced measurement bias in SUV, MTV, and TLG values. Fourth, follow-up duration was limited, preventing robust survival modeling. Finally, this was a single-center study; hence, generalization of findings across diverse clinical settings should be done cautiously until validated by larger multicenter cohorts.

1.         Han S, Choi JY. Impact of 18F-FDG PET, PET/CT, and PET/MRI on staging and management as an initial staging modality in breast cancer: a systematic review and meta-analysis. Clinical nuclear medicine. 2021 Apr 1;46(4):271-82.

2.         Groheux D, Hindie E. Breast cancer: initial workup and staging with FDG PET/CT. Clinical and translational imaging. 2021 Jun;9(3):221-31.

3.         Hyland CJ, Varghese F, Yau C, Beckwith H, Khoury K, Varnado W, Hirst GL, Flavell RR, Chien AJ, Yee D, Isaacs CJ. Use of 18F-FDG PET/CT as an initial staging procedure for stage II–III breast cancer: a multicenter value analysis. Journal of the National Comprehensive Cancer Network. 2020 Nov 2;18(11):1510-7.

4.         Kamal AM, Kamal OA, Sakr HM, Ali SA. Role of 18F-FDG PET/CT in evaluation of recently diagnosed breast cancer patients. Egyptian Journal of Radiology and Nuclear Medicine. 2022 Aug 12;53(1):178.

5.         Groheux D. Breast cancer systemic staging (comparison of computed tomography, bone scan, and 18F-fluorodeoxyglucose PET/computed tomography). PET clinics. 2023 Oct 1;18(4):503-15.

6.         Delgado Bolton RC, Aide N, Colletti PM, Ferrero A, Paez D, Skanjeti A, Giammarile F. EANM guideline on the role of 2-[18F] FDG PET/CT in diagnosis, staging, prognostic value, therapy assessment and restaging of ovarian cancer, endorsed by the American College of Nuclear Medicine (ACNM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the International Atomic Energy Agency (IAEA). European journal of nuclear medicine and molecular imaging. 2021 Sep;48(10):3286-302.

7.         Turan U, Aygun M, Duman BB, Kelle AP, Cavus Y, Tas ZA, Dirim AB, Irkorucu O. Efficacy of US, MRI, and F-18 FDG-PET/CT for detecting axillary lymph node metastasis after neoadjuvant chemotherapy in breast cancer patients. Diagnostics. 2021 Dec 14;11(12):2361.

8.         Morariu DS, Vlad C, Puscas ME, Gata V, Piciu D. Is there a place for F18-FDG PET/CT in the diagnosis of primary breast cancer?. chemotherapy. 2020 Mar 1;13:17.

9.         Su TP, Huang JS, Chang PH, Lui KW, Hsieh JC, Ng SH, Chan SC. Prospective comparison of early interim 18F-FDG-PET with 18F-FLT-PET for predicting treatment response and survival in metastatic breast cancer. BMC cancer. 2021 Aug 10;21(1):908.

10.       Bicakci N. Diagnostic and prognostic value of F-18 FDG PET/CT in patients with carcinoma of unknown primary. Northern Clinics of Istanbul. 2022 Jul 1;9(4).

11.       Kim K, Shim SR, Lee SW, Kim SJ. Diagnostic values of F-18 FDG PET or PET/CT, CT, and US for preoperative lymph node staging in thyroid cancer: a network meta-analysis. The British Journal of Radiology. 2021 Apr 1;94(1120):20201076.

12.       Mirshahvalad SA, Kohan A, Metser U, Hinzpeter R, Ortega C, Farag A, Veit-Haibach P. Diagnostic performance of whole-body [18F] FDG PET/MR in cancer M staging: a systematic review and meta-analysis. European Radiology. 2024 Jan;34(1):673-85.