Global Society of Rare GU Tumors 2020

GSRGT 2020: The Need For Treatment De-Escalation In Advanced Disease: Viewpoint of the Clinical Oncologist

(Urotoday.com) The newly formed Global Society of Rare Genitourinary Tumors (GSRGT) held its inaugural meeting, focusing on penile and testicular cancer. The session held Saturday, December 12th focused on testis cancer. In this session, Dr. Yohann Loriot presented a clinical oncologist’s perspective on the need for treatment de-escalation in advanced disease.

He began by highlighting key questions and challenges in the care of patients with germ cell tumors:

1. how to ensure the delivery of best practices for all patients.
2. how to reduce treatment burden, particularly with long-term side effects of cisplatin-based chemotherapy.
3. how to cure more patients with poor-prognosis metastatic germ cell tumors.

He began by highlighting data presented by Dr. Silke Gillessen at ESMO 2019 demonstrating that 5-year overall survival was substantially better for patients across all risk groups, compared to the initial 1997 International Germ Cell Cancer Collaborative Group (IGCCCG) figures for patients with metastatic non-seminoma and seminoma. 

Thus, given improving survival, he suggested that the first option to decrease the morbidity of treatment, we should proceed to reduce the number of cycles or doses. Highlighted data from GETUG S99, he used the example of metastatic seminoma to demonstrate that EP x 4 cycles result in a cure for nearly all patients with good-risk disease.


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Similarly, recent data published by Cullen and colleagues in European Urology showed that results following one cycle of BE500P are consistent with those from two cycles of BE360P.

A second approach to consider in terms of proceeding is to use imaging or biology to select patients. He began highlighting data from an observational study from Milan demonstrating a potential role for PET-CT as an interim test for patients with advanced seminoma following two cycles of BEP. These data highlighted that PET-CT based interim response was associated with relapse-free survival. Similar results were seen in a UK-based phase II study. 

Based on this approach, he highlighted the SEMITEP phase II trial which includes patients with good-prognosis metastatic seminoma. Following 2 cycles of EP, patients with undergoing interim PET-CT. Patients with a positive scan receive standard chemotherapy whole those who have a negative scan have de-escalated chemotherapy.

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Among 102 enrolled patients, 99 received their first two cycles of EP, and 98 received interim PET-CT. Of those, 71 had a negative PET-CT and 27 had a positive PET-CT. These 27 with a positive PET-CT, as well as 4 with a negative PET-CT, received standard chemotherapy while the remaining 67 received de-escalated therapy with carboplatin. 

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Using this approach, progression-free survival was high in both groups, and overall survival was 100% in both groups.

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 Notably, this de-intensified chemotherapy approach reduced cumulative toxicity, particularly with respect to peripheral neuropathy and cytotoxicity.


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Dr. Loriot then transitioned to discussing microRNA-371a-3p as a biomarker in this disease, highlighting that it is expressed in more than 90% of germ cell tumors, correlates with clinical stage, and may act as a marker of treatment success. 

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Further, preliminary data indicate that miR371 outperforms both CT and traditional biomarkers though the SWOG S1823 trial will validate the clinical utility of this marker.

Dr. Loriot highlighted that it is clear that we need to reduce the treatment burden in metastatic germ cell tumors and PET-CT and miRNA may offer ways to proceed in advanced seminoma and non-seminoma.

Presented by: Yohann Loriot, MD, PhD, Department of cancer medicine, INSERM U981, Université Paris-Saclay, Villejuif, France

Written by: Christopher J.D. Wallis, MD, Ph.D., Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee @WallisCJD on Twitter during the 1st Global Society of Rare Genitourinary Tumors Virtual Summit, December 11-12, 2020