Revisiting classification in testicular cancer: what has changed?

Two papers* on testicular cancer from the International Germ Cell Cancer Collaborative group (IGCCCG) Update Initiative, published recently in the Journal of Clinical Oncology, underline the importance of revisiting and updating tumour classification systems. Both include large datasets on progression-free (PFS) and overall survival (OS) from 30 institutions or collaborative groups in Europe, North America, and Australia. The project was led by Silke Gillessen and Jörg Beyer.

In the first, with Professor Silke Gillessen, Medical and Scientific Director of the Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland as first author, the group studied data from 9,728 men with metastatic nonseminomatous germ cell tumours (NSGCT) treated with chemotherapy between 1990 and 2013. Nonseminoma and seminoma are the two most common types of testicular cancer. Nonseminoma tumours tend to grow more quickly and are in general less sensitive to treatment than seminoma tumours. About half of all patients with these tumours present with metastatic disease.

“Until now, we have been guided in our treatment decisions by the original classification of the IGCCCG, but this relied on data from patients treated between 1975 and 1990. We wanted to know whether this was still relevant and what might have changed subsequently,” says Prof Gillessen.

Compared with the original IGCCCG publication, five-year PFS remained similar in patients with a good prognosis at 89% vs 90%, while the five-year OS increased from 92% to 96%. In patients with intermediate prognosis, PFS once again remained similar (75% vs 78%), while OS increased from 80% to 89%. In the group with a poor prognosis, there were important increases in PFS (41% to 54%) as well as in OS (48% to 67%).

The researchers found two new prognostic factors – age and the presence of lung metastases. The reasons for the age-related adverse prognosis do not seem to be related to increased treatment-related mortality, they say. “Additionally, we found no evidence that the patients’ ages influenced the choice of treatment”, says Prof Gillessen. “We believe that the treatment of older patients with this type of tumour should be a focus in future clinical studies.”

Despite the improvements in OS of patients with NSGCT, more than 30% of patients with poor prognostic factors may still die of their disease. “The original IGCCCG classification is still relevant, which is an important finding. We are pleased to have been able to discover additional adverse prognostic factors, and the calculator based on these findings allows a more granular prognosis for an individual patient,” says Prof Gillessen. “We now have a huge database that will enable us to address additional questions. We intend to share our algorithm so that others can conduct external validation studies to look at such questions as, for example, whether our model is applicable to patients of different ethnicities or paediatric patients.”

In the second paper the same group of researchers, with Professor Jörg Beyer, head of Medical Oncology at the Inselspital Bern, Bern, Switzerland as first author, re-evaluated IGCCCG data on patients with seminoma. The original classifications were based on only 660 patients, treated between 1975 and 1990. For the new analysis, data on 2,451 men with metastatic seminoma treated with chemotherapy between 1990 and 2013 were included.

Once again, the researchers found significant improvements in both PFS and OS. In those men with a good prognosis, PFS rose from 82% to 89%, and five-year OS from 86% to 95%. In intermediate prognosis PFS went from 67%, to 79%, and OS from 72%, to 88%. Elevated lactate dehydrogenase (LDH), an enzyme expressed as a result of tissue damage, was found to be an additional adverse prognostic factor within the good prognosis group. “This is an important finding that will allow us to further refine treatment strategies for these patients,” says Prof Beyer, “mainly to pursue de-escalation strategies in patients without any adverse prognostic factors who have excellent outcomes with current modern-type treatments.”

“These two studies underline the value of international academic collaboration combining real-world evidence with that from randomised trials. There are few organisations with the capacity to do this, and it is an area where EORTC can really make a difference to patients’ lives.”

* https://ascopubs.org/doi/full/10.1200/JCO.20.03296

https://ascopubs.org/doi/full/10.1200/JCO.20.03292

The research was funded by Movember, the EORTC Genito-urinary Cancer Group, and the Swiss Cancer Foundation.