The doubling in KIM-1 plasma concentration was significantly associated with an increased risk for RCC — for each 2-fold increase in KIM-1 plasma concentration, the risk for RCC increased with an incident rate ratio (IRR) of 1.71 (95% CI, 1.44-2.03; P = 4.1 x 10-23). There was little change in IRR when adjusted by smoking status, sex, age at baseline, body mass index, hypertension, or diabetes. When comparing the 80th (199.04 pg/mL) to 20th percentile (undetected concentration) of KIM-1 concentration, the IRR for RCC was 63.3 (95% CI, 16.2-246.9).
The association was accurately detected up to 5 years prior to RCC diagnosis, with a similar IRR for cases diagnosed within 2 years (IRR, 1.82; 95% CI, 1.38-2.50) or between 2 to 5 years before diagnosis (IRR, 1.63; 95% CI, 1.30-2.05).
Adding KIM-1 to a risk model that included age, sex, country, body mass index, and smoking status improved the discrimination of the model between RCC cases and controls by increasing the area under the curve from 0.7 to 0.8, increased the sensitivity from 42% to 76% for a specificity of 75%, or from 21% to 54% for a specificity of 95%.
KIM-1 concentration was also associated with outcomes after RCC diagnosis. There was a nonlinear association between increasing KIM-1 concentration (50 pg/mL used as referent) and risk of death, with a hazard ratio of 1.45 (95% CI, 1.12-1.86) for 100 pg/mL and 3.29 (95% CI, 1.61-6.74) for 800 pg/mL.
Dr Bhatt said that the results from this study demonstrate that KIM-1 holds “promise for a biomarker in kidney cancer,” but, she highlighted that, “this is not yet a validated marker and more studies are definitely needed.” KIM-1 is not yet ready to be used in the clinic as a screening test or for clinical decision-making.
If additional studies confirm the results of the present study and KIM-1 is validated as a biomarker, Dr Bhatt said that “KIM-1 may be useful in making clinical decisions about people who have already been diagnosed with RCC.”
Another goal for KIM-1 is using it as part of a multivariable model. “The future hope is that it may show some utility and aid in the diagnosis of kidney cancer combined with other relevant tests,” Dr Bhatt said.
The next step, according to Dr Bhatt, is to “incorporate KIM-1 into studies in higher risk populations, such as patients who have already been diagnosed with RCC, to help determine next steps in their care.”
KIM-1 is currently not being developed as a screening test. Dr Bhatt pointed out that the low incidence of RCC suggests that KIM-1, even if validated, may not be ready to use for screening a general population. “It is sort of analogous to the PSA story — PSA detects prostate cancer, but it’s very controversial in screening for prostate cancer; however, once a patient has prostate cancer, it’s very useful as a marker,” she said.
- Scelo G, Muller DC, Riboli E, et al. KIM-1 as a blood-based marker for early detection of kidney cancer: a prospective nested case-control study [published online July 23, 2018]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-1496