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Primary NSCLC may be underdiagnosed among patients with metastatic renal cell carcinoma
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More than 3% of patients with kidney cancer that metastasized to the lungs subsequently were found to have primary lung cancer, according to results of a retrospective review published in Clinical Genitourinary Cancer.
“Kidney cancer spreads primarily to the lungs, making the detection of a primary lung cancer difficult,” James Brugarolas, MD, PhD, director of the kidney cancer program at UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, said in a press release. “Lung cancer is typically more aggressive than kidney cancer. Undetected, lung cancer may spread and eventually kill the patient.”
Brugarolas and colleagues assessed the frequency with which patients who had renal cell carcinoma metastasize to the lungs subsequently received non–small cell lung cancer diagnoses.
The study included 151 patients who received systemic targeted therapy for metastatic renal cell carcinoma.
In the entire cohort, three patients (2%; 95% CI, 0.68-5.68) subsequently received an NSCLC diagnosis. When researchers limited their analysis to patients with known renal cell carcinoma pulmonary metastases, the incidence of subsequent NSCLC diagnoses increased to 3.5% (95% CI, 1.21-9.87). This equated to an incidence rate for NSCLC development among patients with metastatic renal cell carcinoma of 0.87 (95% CI, 0.22-2.4) per 100 person-years.
HemOnc Today spoke with Brugarolas about the study results, their implications, and the potential biologic association between kidney cancer and lung cancer.
Question: How did you conduct this study?
Answer: We conducted a retrospective review of patients with kidney cancer. We gathered our data between January 2006 and October 2013, and we identified all patients who had received systemic targeted therapy for kidney cancer at our institution. This was based upon a cohort of patients that we submitted to the International Metastatic Database Consortium.
Q: What did you find?
A: Three of 85 patients with renal cell carcinoma metastatic to the lungs had a primary lung cancer. This is significant. It may not appear as a big number, but it is significantly higher than expected.
Q: Did the findings surprise you?
A: It was surprising because there is no published scientific literature on this, and it is not something that genitourinary oncologists are looking for in their patients. When we see a patient with lung nodules, we tend to think it is kidney cancer that has metastasized to the lung. We do not typically think of another independent, undiagnosed primary cancer.
Q: What are the potential explanations of your findings?
A : There is clearly a shared environmental exposure, which is tobacco smoking. This is a known risk factor for both renal cell carcinoma and lung cancer. It is worth mentioning, however, that one of the patients with both renal cell carcinoma and NSCLC never smoked, so there likely are other risk factors involved.
Q: Can you speculate on what these other risk factors may be?
A: When we think about cancer, we consider genetics and the environment. There could be other environmental exposures that exert influence that is less significant than tobacco smoking. There are genetic factors that also could be at play. A lot of progress has been made in this area with the advent of next-generation sequencing. However, most of the genes frequently mutated in clear cell renal cell carcinoma at the somatic level are rarely associated with lung cancer.
Q: Can you offer more insight into potential biologic factors that might contribute to an association between ki dney cancer and lung cancer?
A: There are familial syndromes that predispose people to kidney cancer. However, lung cancer is rarely observed in these patients. This does not exclude the fact that there may be genes that exert minor contributions and predispose to both kidney and lung cancer.
Q: Can you put into context how compelling the 3.5% rate is?
A: If we estimate that there are 15,000 patients in the United States with renal cell carcinoma metastatic to the lungs, then we are talking more than 500 patients [with a primary NSCLC]. One of my patients died of metastatic lung cancer, and he was diagnosed with lung cancer after he was diagnosed with kidney cancer. Raising awareness that some patients may have two different primaries is important, and it can save lives.
Q: Should anything change in clinical practice based upon these findings?
A: I hope these findings will increase awareness about the possibility that patients may have both kidney and lung cancer. Oncologists and radiologists must be more aware of this, but patients also need to be more aware so they can advocate for themselves.
Q: Is there anything else that you would like to mention?
A: Please consider that there could be a hidden NSCLC primary in patients you treat for metastatic renal cell carcinoma. Identifying this second primary is particularly difficult in patients who have metastases from renal cell carcinoma. If you see a nodule that looks different than the rest — particularly if it is speculated, has a pleural tag or air bronchograms — it may be NSCLC. Another warning sign may be the presence of an isolated lung lesion that is not responding to treatment. – by Jennifer Southall
Reference:
Brugarolas J, et al. Clin Genitourin Cancer. 2017;doi:10.1016/j.clgc.2017.01.026.
For more information:
James Brugarolas, MD, PhD, can be reached at Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390; email: james.brugarolas@utsouthwestern.edu.
Disclosure: Brugarolas reports no relevant financial disclosures.