Expression of PD-L1 in Renal Cancer, Prognostic Features and Clinical Utility of Its Routine Staining

Oncologic therapies are advancing at a great speed, there is a new drug, a combination of drugs, or new trials every other month. Urology is not the exception, and this demands urologists to be up to date to deliver appropriate treatment. The concept of appropriate treatment can be somehow vague, but it should involve taking into account as many factors as possible before prescribing any therapy. This includes patients' preferences, family history, performance status, histology, tumor stage, costs, quality of life, genetics, and others. The point is to tailor the treatment according to each case.

Systemic therapy for kidney cancer has evolved significantly in the last decade, from TKI and mTOR to ICI, ICI + ICI, ICI + TKI, and new TKIs, with some amazing results but at the expense of great economic burden. In kidney cancer, we lack new prognostic and predictive tools that allow us to choose the most convenient alternative for the patient and health system. Drugs keep on coming, but no new marker that reliably tells us which patient will do better with which drug, and in whom the effect will be such that the cost of therapy makes it inappropriate, has yet been established.

In light of these situations, we aimed to investigate if we could enhance our kidney cancer patients' care, with the diagnostic tools we have available now. We chose as a starting point PD-L1 immunohistochemistry (IHC) analysis as most ICI for kidney cancer are directed at the PD-1/PD-L1 axis. And we observed, in this retrospective analysis, that PD-L1 positive patients have worse overall and cancer-specific survival compared to PD-L1 negative. So, routine PD-L1 IHC analysis provides us with valuable information for counseling our patients, as a prognostic marker.

Many will argue that it has no value as it does not change management, there are some technical difficulties with the IHC technique and there are differences in PD-L1 expression between the primary tumor and its metastasis. All of these are true, but this does not mean that a relatively simple test, not expensive, can objectively aid us in the care of our patients and the administration of resources. Some studies have observed that PD-L1 positive patients have a greater response to ICI than PD-L1 negative, opposite to what happens with TKI, where PD-L1 negative do better. So, in places where access to ICI is limited, PD-L1 could be used to detect the patient that will benefit the most from such expensive therapy. Also, although not yet studied as far as we have research, we see it feasible to incorporate PD-L1 staining in protocols of active surveillance (AS). For example, a good candidate for AS but with high PD-L1 in the biopsy may be better managed with surgery.
We believe there is still much to be discovered that will help us treat better and at the same time be reasonable with costs. Genetic tests are now trending but costs are still high, while IHC is of moderate cost and has been validated for many years now.

Written by: Ragheb Massouh Skorin, MD, Department of Urology, Hospital Clínico San Borja Arriarán, Santiago, Chile

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