The application of 18F-FDG PET/CT in malignant melanoma is extensive in terms of diagnosis[13,14], stage[15,16] and therapeutic evaluation[17,18], while few prognostic studies have been reported. Tumor glycolytic activities on 18F-FDG PET have significant and independent value in predicting primary CMM[11,19] and metastatic malignant melanoma[12,20], while studies on metastatic CMM are rare. Meanwhile, regarding metabolic PET parameters, previous studies mainly focused on SUVmax, MTV (wMTV) and TLG (wTLG). In contrast, datas on the prognostic value of SUVmean in metastatic CMM are limited. In our study, all four metabolic PET parameters (SUVmax, SUVmean, wMTV and wTLG) were measured to evaluate the utility of 18F-FDG PET/CT in detecting recurrence and predicting survival in patients with metastatic CMM. This retrospective study indicated that SUVmax was an independent prognostic factor for DFS and that SUVmax, wMTV and wTLG were independent prognostic factors for MSS in patients with metastatic CMM, even after adjustment for the effects of clinical parameters.
SUVmax, a well-known digitized PET parameter, has been used to evaluate the likelihood of aggressive disease, the metabolic response to therapy, the early detection of disease recurrence and prognosis. Higher SUVmax is correlated with tumor cell proliferation and poor prognosis. This study demonstrated that SUVmax was an independent prognostic factor for both DFS and MSS in patients with metastatic CMM. The only previous study including the metabolic PET parameter of SUVmax in metastatic CMM patients was that of Seban, R. D et al.[21], who reported that wMTV rather than SUVmax was the best predictive marker of MSS. They studied a cohort of 32 patients treated with immune checkpoint inhibitors (ICIs), while ours was a cohort of 42 patients treated with traditional treatment, which may cause different results. In addition, tumor shapes can be variable and asymmetrical, particularly in metastatic cancer. Furthermore, tumor composition and intratumoral FDG uptake can be heterogeneous because of cells with high or low metabolism, such as necrotic tissue or fibrotic scarring[22,23].
This study also analyzed the prognostic value of SUVmean, which is infrequently used. In a study of 80 patients with stage IIIB melanoma, Bastiaannet, E et al.[20] found that the 5-year disease-free survival rates in patients with a low mean SUV and in those with a high mean SUV were 40.9% (95% CI, 25.5–55.7%) and 24.2% (95% CI, 12.4–38.0%), respectively (p = 0.02). The mean SUV was associated with DFS but was not associated with DSS, which was consistent with our results. These results showed that SUVmean could potentially be a useful factor in the prognostic evaluation of metastatic melanoma for both stage III and stage IV.
We concentrated on volumetric and metastatic PET parameters (wMTV, wTLG) that could evaluate patients at high risk of recurrence and death. In this study, the multivariate analysis showed that wMTV and wTLG were significant independent prognostic factors for melanoma-specific survival, even after adjusting for clinical prognostic factors in patients with metastatic CMM. wMTV and wTLG, which quantify the overall tumor burden and represent information about both tumor volume and metabolic activity, respectively[11,26], have been investigated in many tumors, such as nasopharyngeal carcinoma[27], lymphoma[28], breast cancer[29] and lung cancer[30,31]. In this study, wMTV and wTLG were the best predictive factors for MSS but not DFS. These results indicated that metastatic CMM patients with high wMTV and wTLG experience shorter overall survival, even when they have the same clinical factors. Seban, R. D et al.[21] reported 32 patients with metastatic CMM treated with immune checkpoint inhibitors targeting PD-1, and they found that the baseline wMTV and TLG were significant independent prognostic biomarkers for OS in multivariate analysis. The median OS was 28.3 (95% CI 8.9–44.8), and 20 out of 32 patients died. TMTV and TLG were significantly associated with poor OS (TMTV: HR 1.0, p = 0.009; TLG: HR 1.0, p = 0.009). Seban, R. D et al. also investigated whether wMTV was a significant independent prognostic biomarker for PFS, and their results were not consistent with our results. The median follow-up was 29.9 months, while ours was 38.6 months; moreover, Seban, R. D et al.’s study used treatment only targeting PD-1, while ours used single or combination treatment, which may be the reason for the different results. Ito, K. et al.[12] also emphasized the important prognostic role of wMTV in metastatic melanoma patients treated with immune checkpoint inhibitors targeting CTLA-4 (ipilimumab). They found that wMTV was a strong independent prognostic factor for OS (p = 0.001), which was also consistent with our results.
We recognize several limitations of this study. First, a limited number of patients were included in this retrospective study, which may explain the absence of a strong association between PET metabolic biomarkers (especially wMTV and wTLG) and PFS; therefore, further validation studies are needed in a larger cohort of metastatic CMM patients. Second, to assess tumor burden, MTV was determined as the volume enclosed by a 40% isocontour around the maximum PET voxel of the tumor lesions in this study as described by some studies, while the volume of voxels with a threshold SUV of 42% or greater of the SUVmax was also determined by other studies[11,12]. The most appropriate segmentation method for estimating MTV and TLG is still debated.