Higher Rates of Nephrectomy in Patients With RCC With Prior Thymectomy

Regina Barragan-Carrillo, MD

Significantly higher rates of nephrectomy were observed in patients with renal cell carcinoma (RCC) who received prior thymectomy compared with the incidence of nephrectomy overall, according to findings from a large population-based study.

The study sought to compare patients who underwent thymectomy and nephrectomy, and experts examined various demographic and clinical characteristics. According to Regina Barragan-Carrillo, MD, a larger proportion of patients undergoing nephrectomy were male (57% vs 45%) and Hispanic vs those undergoing thymectomy (28% vs 18%; P <.01).

When expressed as a percentage of the underlying age-matched population, a much smaller percentage of patients received thymectomy compared with nephrectomy (0.01% vs 0.17%). Among the patients who underwent thymectomy, 11 of them later underwent nephrectomy. This suggests an incidence rate of 0.56% for nephrectomy in the thymectomy cohort. Notably, this incidence rate was significantly higher than the incidence of nephrectomy in the general population (P =.002).

Moreover, the median age of patients who had a nephrectomy for RCC after undergoing a prior thymectomy was 52 years vs 57 years for the general population undergoing nephrectomy.

In an interview with Targeted Oncology^TM, Barragan-Carrillo, medical oncologist, postdoctoral fellow, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, discussed the background and findings from this study comparing patients who underwent thymectomy and nephrectomy.

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Targeted Oncology: What can you discuss regarding your work on the association between thymectomy and incidence of renal cell carcinoma?

Barragan-Carrillo: It is very important during the development of the immune system during childhood, and it usually occurs during the teenage years. But in adulthood, the role of the thymectomy was quite unclear. Recently, back in 2023, there was a paper published in the New England Journal of Medicine addressing the role of the thymus in adult life, and what they noticed is that there was an increase in overall mortality in patients who underwent at thymectomy in their adult life when compared with controls, which were quite surprising results like after having this dogma for the past 200 years. Additionally, they also noticed that there was an increase in the rate of cancer diagnosis, number of cancers per patient, and cancer-related mortality in patients who did not have the thymic tissue.

It is important to note that these results are secondary malignancies or any other malignancies associated within the thymic tissue. So, I think these results are surprising and even, for example, looking at the type cancers that were reported, those did not follow what we classically see worldwide, so that was also an important factor. We have noticed, mostly in the last 15 years, that renal cell carcinoma is a tumor that is highly exquisite to be treated with immunotherapy. Mostly standard care is currently based on immune checkpoint inhibitors in combination with another CTLA4 inhibitor or [tyrosine kinase (TKI)]. So, it has a very unique biology.

This sensitivity to immunotherapy, unlike other neoplasms, does not stem from [the tumor microenvironment (TME)] or does not stem from mismatch repair deficiency, but from at least part from a particular tumor microenvironment, which characterized by an important infiltrate of lymphocytes, which exceeded this classical phenotype of immune exhaustion. We saw the connection between those 2, and we asked ourselves the question whether these patients who had had the history of a thymectomy during their adult life would be at a higher risk to develop renal malignancies.

What specific end points did the study test?

For the end points, we tested for the rate of nephrectomies, or renal cell diagnosis specifically. How we did this and how we chose that is because of the methodology we had available. We used the [California Office of Statewide Health Planning and Development (OSHPD)] database, which is the standard for the office of statewide planning and development which is a database based in California [and] accounts for all the procedures that are done in the inpatient and outpatient settings and also for all ER visits. What we have seen with the information available are the procedures through the CPT and ICD-9/10 codes.

What we decided is to use the coding for thymectomy and the coding for nephrectomy to identify both groups. For example, the rate we have in the state of California accounting for all adult patients, meaning 40 years or older, the rate we have for nephrectomy for renal cell carcinoma is around 0.2%. The rate we noticed in those patients who had previously undergone a thymectomy was 0.56%, which is more than double what we would have expected for the state of California.

One might raise the question, and I think it is a valid question, is whether there was a risk of bias in the selection of the population because these are patients who are already under certain scrutiny because of their past surgical history. We included in our analysis another 3 surgical procedures, which were a cholecystectomy, a hip arthroscopy, and a knee arthroscopy. In all 3 subpopulations who had undergone those procedures and afterwards required nephrectomy for RCC, the rates for RCC after diagnosis were also pretty similar to what we saw in the overall population, which were around 0.20%. Which also, historically, are the numbers that make sense in that regard. The difference between the patient with a prior time made to me was quite clear to us.

What is the main takeaway from this study?

The main takeaway is that this is only hypothesis generating. We still need to make a lot of efforts to understand whether there is an association of causation between those 2, but at least it raises the question to know whether patients that are in this nonclassical immunosuppressive state who have a higher risk to develop other secondary malignancies. We ask the clinical team as the healthcare providers could appropriately counsel these patients during their follow-up.

Do you plan to conduct any further research to explore this association?

Yes, we are planning to do that. This is an optimistic first step to take at least to know whether there is something we have not seen in the last couple of years that we might explore. But yes, we are planning to take further steps in this.

REFERENCE:

Barragan-Carrillo R, Ebrahimi H, Chawla NS, et al. Association between thymectomy and incidence of renal cell carcinoma (RCC). J Clin Oncol. 2024;42(suppl 4):371. doi:10.1200/JCO.2024.42.4_suppl.371