Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I-II Melanoma Patients at Risk of Disease Relapse

Evalyn E A P Mulder; Iva Johansson; Dirk J Grünhagen; Dennie Tempel; Barbara Rentroia-Pacheco; Jvalini T Dwarkasing; Daniëlle Verver; Antien L Mooyaart; Astrid A M van der Veldt; Marlies Wakkee; Tamar E C Nijsten; Cornelis Verhoef; Jan Mattsson; Lars Ny; Loes M Hollestein; Roger Olofsson Bagge

doi:10.3390/cancers14122854

Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I-II Melanoma Patients at Risk of Disease Relapse

Cancers (Basel). 2022 Jun 9;14(12):2854. doi: 10.3390/cancers14122854.

Authors

Evalyn E A P Mulder^{1

2}, Iva Johansson^{3

4}, Dirk J Grünhagen¹, Dennie Tempel⁵, Barbara Rentroia-Pacheco⁵, Jvalini T Dwarkasing⁵, Daniëlle Verver¹, Antien L Mooyaart⁶, Astrid A M van der Veldt^{2

7}, Marlies Wakkee⁸, Tamar E C Nijsten⁸, Cornelis Verhoef¹, Jan Mattsson⁹, Lars Ny^{4

10}, Loes M Hollestein^{8

11}, Roger Olofsson Bagge^{9

12

13}

Affiliations

¹ Departments of Surgical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
² Departments of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
³ Departments of Pathology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
⁴ Departments of Oncology, Institute of Clinical Sciences at Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden.
⁵ SkylineDx B.V., 3062 ME Rotterdam, The Netherlands.
⁶ Department of Pathology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
⁷ Departments of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
⁸ Departments of Dermatology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
⁹ Departments of Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
¹⁰ Departments of Oncology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
¹¹ Department of Research, Netherlands Comprehensive Cancer Organization (IKNL), 3511 DT Utrecht, The Netherlands.
¹² Departments of Surgery, Institute of Clinical Sciences at Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden.
¹³ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.

Abstract

Background: The current standard of care for patients without sentinel node (SN) metastasis (i.e., stage I−II melanoma) is watchful waiting, while >40% of patients with stage IB−IIC will eventually present with disease recurrence or die as a result of melanoma. With the prospect of adjuvant therapeutic options for patients with a negative SN, we assessed the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict SN metastasis, to identify patients with stage I−II melanoma at risk of disease relapse. Methods: This study included patients with cutaneous melanoma ≥18 years of age with a negative SN between October 2006 and December 2017 at the Sahlgrenska University Hospital (Sweden) and Erasmus MC Cancer Institute (The Netherlands). According to the CP-GEP model, which can be applied to the primary melanoma tissue, the patients were stratified into high or low risk of recurrence. The primary aim was to assess the 5-year recurrence-free survival (RFS) of low- and high-risk CP-GEP. A secondary aim was to compare the CP-GEP model with the EORTC nomogram, a model based on clinicopathological variables only. Results: In total, 535 patients (stage I−II) were included. CP-GEP stratification among these patients resulted in a 5-year RFS of 92.9% (95% confidence interval (CI): 86.4−96.4) in CP-GEP low-risk patients (n = 122) versus 80.7% (95%CI: 76.3−84.3) in CP-GEP high-risk patients (n = 413; hazard ratio 2.93 (95%CI: 1.41−6.09), p < 0.004). According to the EORTC nomogram, 25% of the patients were classified as having a ‘low risk’ of recurrence (96.8% 5-year RFS (95%CI 91.6−98.8), n = 130), 49% as ‘intermediate risk’ (88.4% 5-year RFS (95%CI 83.6−91.8), n = 261), and 26% as ‘high risk’ (61.1% 5-year RFS (95%CI 51.9−69.1), n = 137). Conclusion: In these two independent European cohorts, the CP-GEP model was able to stratify patients with stage I−II melanoma into two groups differentiated by RFS.

Keywords: clinicopathologic and gene expression model; primary cutaneous melanoma; risk stratification recurrence.

Grants and funding

Netherlands Enterprise Agency