eUpdate – Testicular Seminoma and Non-Seminoma Treatment Recommendations
Published: 9 January 2020. Authors: Jan Oldenburg, Tom Powles and Silke Gillessen on behalf of the ESMO Guidelines Committee
Note: Other eUpdates have been published for these guidelines. All currently valid eUpdates can be accessed from the page displaying the full guidelines on this topic.
Clinical Practice Guidelines
This update refers to the Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Oldenburg J, Fosså SD, Nuver J et al, Ann Oncol 2013; 24 (Suppl 6): vi125–vi132
The original paragraph “Stage IS/II/III” is replaced with:
The GETUG 13 study by Fizazi et al. addresses two unmet medical needs: prospective assessment of the impact of poorly declining tumour markers [alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG)] as well as identification of a chemotherapy regimen superior to bleomycin, etoposide and cisplatin (BEP) x 4 cycles for treatment of patients with metastatic poor-risk non-seminomatous germ cell tumours and an unfavourable marker decline . Of 254 patients, 51 (20%) had a favourable marker assessment, and 203 (80%) had an unfavourable tumour marker decline.
Patients with a favourable marker decline after the first cycle of BEP received 3 additional BEP cycles, i.e. standard chemotherapy. The patients with unfavourable marker decline (n= 105) were randomly assigned to receive 3 additional BEP cycles versus a dose-dense regimen comprising BEP with continuous bleomycin infusions over 5 days with additional paclitaxel, ifosfamide and oxaliplatin, with granulocyte-colony stimulating factor support (for detailed description of the regimen refer to ).
As hypothesised, patients with favourable marker decline had superior progression-free survival (PFS) than those with unfavourable marker decline: 3-year PFS of 70% versus 48%, hazard ratio [HR] 0.66. Among patients with unfavourable marker decline, the patients treated with the dose-dense regimen demonstrated a significantly better 3-year PFS than those treated with standard BEP of 59% versus 48% (HR 0.66, 95% confidence interval (CI) 0.44–1.00, P=0.05).
The dose-dense regimen caused relevant neuro- and haematotoxicity but did not cause more grade 1–2 febrile neutropaenia or toxic deaths. Among patients with unfavourable marker decline, salvage high-dose chemotherapy was required in 6% and 16% of patients after the dose-dense regimen and standard BEP x 4 cycles, respectively.
Online calculation of marker decline: https://www.gustaveroussy.fr/calculation-tumor/NSGCT.html. There is also an app for smart phones.
In patients with a poor-risk non-seminoma, the AFP and HCG decline should be assessed after one cycle of BEP. Patients with an unfavourable marker decline should be considered for treatment with the dose-dense regimen as in GETUG-13 [I, B].
However, superiority was demonstrated only for PFS and not overall survival (OS). While the role of unfavourable marker decline has been irrevocably established as a prognostic factor, the extrapolation of this data to alternative dose-dense regimens or high-dose chemotherapy that is considered reasonable by some experts is not supported by evidence [V, D].
- Fizazi K, Pagliaro L, Laplanche A, Flechon A, Mardiak J, Geoffrois L, et al. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. The Lancet Oncology. 2014;15(13):1442–50.