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Multicenter Study
. 2023 Aug;12(16):16829-16836.
doi: 10.1002/cam4.6304. Epub 2023 Jul 1.

Misuse of tumor marker levels leads to an insufficient International Germ Cell Consensus Classification (IGCCCG) risk group assignment and impaired treatment

Matthäus Majewski  1 , Pia Paffenholz  2 , Christian Ruf  1 , Yue Che  3 , Christoph Seidel  4 , Julia Heinzelbecker  5 , Hans-Ulrich Schmelz  6 , Cord Matthies  7 , Peter Albers  3 , Carsten Bokemeyer  4 , Axel Heidenreich  2   8 , Martin Pichler  9 , Tim Nestler  2   6 ; GTCSG (German Testicular Cancer Study Group)
Affiliations
Multicenter Study

Misuse of tumor marker levels leads to an insufficient International Germ Cell Consensus Classification (IGCCCG) risk group assignment and impaired treatment

Matthäus Majewski et al. Cancer Med. 2023 Aug.

Abstract

Background: Metastatic germ cell tumors of the testis (GCTs) are risk-stratified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system. This risk classification is based on anatomical risk factors as well as tumor marker levels of AFP, HCG, and LDH assessed pre-chemotherapy after orchiectomy treatment. An incorrect classification is possible when pre-orchiectomy marker levels are used, possibly resulting in over- or undertreatment of patients. The aim was to investigate the potential frequency and clinical relevance of incorrect risk stratification using pre-orchiectomy tumor marker levels.

Methods: A multicenter registry analysis, including patients with metastasized nonseminomatous GCT (NSGCT), was conducted by investigators of the German Testicular Cancer Study Group (GTCSG). Based on the marker levels at different timepoints, IGCCCG risk groups were calculated. The agreement was tested using Cohen's kappa.

Results: A total of 672 of 1910 (35%) patients were diagnosed with metastatic NSGCTs, and 523 (78%) had sufficient data for 224 follow-up data points. By using pre-orchiectomy tumor marker levels, 106 patients (20%) would have been incorrectly classified. Seventy-two patients (14%) were classified into a higher risk category, and 34 patients (7%) were classified into a lower risk category. Cohen's kappa was 0.69 (p < 0.001), showing a strong agreement between the use of both marker timepoints. The treatment of misclassified patients would have resulted in an overtreatment of 72 patients or undertreatment of 34 patients.

Conclusions: The use of pre-orchiectomy tumor marker levels may lead to an incorrect risk classification and might subsequently lead to under- or overtreatment of patients.

Keywords: AFP; IGCCCG; LDH; NSGCT; hCG; metastasis; serum tumor marker; testicular germ cell tumor.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram for patient selection.
FIGURE 2
FIGURE 2
Therapeutic consequences using pre‐orchiectomy instead of pre‐chemotherapy marker levels. BEP, bleomycin, etoposide, and cisplatin. Figure displaying the total number and resulting consequence of using pre‐orchiectomy instead of pre‐chemotherapy markers. Definite overtherapy is displayed in orange, possible overtherapy is showed in pale orange. Definite undertherapy is displayed in blue, possible undertherapy is showed in pale blue. BEP = Bleomycin (B), Etoposid (E) and Cisplatin (P).
FIGURE 3
FIGURE 3
Marker responsible for changes in the IGCCCG risk group. Venn diagram visualizing the causal markers for the change in IGCCCG risk group classification. AFP, alpha‐fetoprotein, hCG, human chorionic gonadotropin, LDH, lactate dehydrogenase.
See this image and copyright information in PMC

References

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