JOURNAL CLUB-brief review

Are NSAIDs Linked to an Increased Risk of Kidney Cancer?

Published September 12, 2011 in the Archives of Internal Medicine (1) is a report by Eunyoung Cho et al from the Channing laboratory at the Brigham and Women’s Hospital and Harvard Medical School. The study associates the long-term use of NSAIDs with an increased risk of renal cancer. Renal cancer (RCC) is the seventh leading cancer in men and the ninth commonest cause of cancer in women in the United States. Linking the risk of cancer with exposure to non-steroidal anti-inflammatory agents (NSAIDs) would naturally draw wide interest, as it already has. 

Cho and colleagues conducted a prospective study to examine the relationship between analgesic use and renal cancer risk. This is the first prospective study of nonaspirin NSAIDs and the largest prospective study of analgesics in relation to renal cancer risk.

The advantage of the prospective design is that it minimizes biases that can affect case-control studies. The study was also unique in that it had information on the use of analgesics ascertained multiple times during follow-up. This enabled the investigators to calculate duration of use and the strength of the association with analgesic use, as compared to use at baseline.

Cho and colleagues utilized two well characterized databases: the Nurses’ Health Study and the Health Professionals Follow-up Study.

The sample sizes were large – 77,525 women followed for 16 years and 49,403 men followed for 20 years.

The investigators conducted separate analyses for each cohort, tested for heterogeneity between studies, and applied meta-analytic methods with a random-effects model to pool the relative risks from the cohorts.

The main findings of the study were:

• They documented 333 cases of RCC (153 women and 180 men).
• Aspirin and acetaminophen use were not associated with renal cancer risk.
• Regular use of nonaspirin NSAIDs at baseline was associated with an increased renal cancer risk; the pooled multivariate RR was 1.51 (95% CI, 1.12-2.04), compared with nonregular use. The results did not differ by sex.
• There was a linear increase in renal cancer risk in women by increasing frequency of use (in women, they had more detailed information on frequency of nonaspirin NSAID use). Compared with non-use, the relative risks were:
•    1.08 (95% CI, 0.67-1.74) use of 1-4 days per month
•    1.30 (0.71- 2.39) use of 5-14 days per month,
•    1.86 (1.19-2.90) use >15 times per month,
• The absolute risk differences for the users vs. nonusers of nonaspirin NSAIDs were 9.15 per 100 000 person-years in women and 10.92 per 100 000 person-years in men.
• There was a dose-response relationship between duration of regular use of nonaspirin NSAIDs and renal cancer risk; compared with nonregular use- the pooled multivariate RRs were:
• 0.81 (95% CI, 0.59-1.11) for use <4 years,
• 1.36 (0.98- 1.89) for 4 -10 years
• 2.92 (1.71-5.01) for >10 years (P<.001 for trend).        
• There was no relation to any specific type of renal cancer
• Aspirin was not associated with an increase risk of RCC

The study had potential limitations (residual confounding, potential for confounding by indication), but these were acknowledged by the authors and discussed in the paper. The risk is also quite modest

Bottom-line

This is an excellent study, well designed and using 2 well-characterized cohorts. The absolute risk of NSAIDS causing renal cancer is quite low. Patients who need to take NSAIDs will continue to take them because there are no alternatives out there that could easily substitute for NSAIDs that are associated with lower risk. In fact, as the authors discuss, assuming a causal relation, the use of nonaspirin NSAIDs by each of 10,929 women or 9,158 men would lead to 1 renal cancer case (the numbers needed to harm). However, since NSAIDs are used by many millions of people in the US, some using them very regularly, this does represent a potentially meaningful risk when applied across the population as a whole.

The study does add to the growing list of adverse effects of NSAIDs and also behooves us to add habitual/regular use of NSAIDs to the list of risk factors we ask about when we evaluate a patient for a potential renal cell cancer.

References

1. Cho E, Curhan G, Hankinson SE, Kantoff P, Atkins MB, Stampfer M, Choueiri TK Prospective Evaluation of Analgesic Use and Risk of Renal Cell CancerArch Intern Med. 2011;171(16):1487-1493