(UroToday.com) The International Kidney Cancer Symposium 2021 annual hybrid meeting included a non-clear cell renal cell carcinoma (RCC) session and a presentation by Dr. Ivan Pedrosa discussing phenotypic characterization of renal masses by a virtual biopsy approach. Dr. Pedrosa notes that many renal masses are found incidentally, typically by a single-phase ‘total body’ contrast-enhanced CT scan (not a typical renal phase CT scan), and thus may not be completely characterized. The imaging dilemma after a single-phase contrast-enhanced CT scan is that we may not know if the renal mass is a malignancy and the patient requires a pre- and post-contrast CT, an MRI or an ultrasound.
Approximately 70% of kidney cancers are diagnosed as an ‘incidental’ finding on imaging and at early stages at diagnosis. As such, over the last several years, kidney cancer incidence has increased markedly from 7.1/100,000 in 1975 to 14.9/100,000 in 2016, secondary to this increased utilization of abdominal imaging. Several specific examples include 27% of healthy patients undergoing an MRI having renal cysts and 14% of patients undergoing a low-dose unenhanced CT for colon cancer screening having a renal mass. Taking this data into context, Dr. Pedrosa summarized that among 3,000 patients, 420 will have renal masses, 50 (2%) will be indeterminate, and 5 will be RCC (0.2%).
The most recent update (2021) of the AUA guideline on renal masses and localized renal cancer1 emphasizes that the evaluation and diagnosis of a renal mass should include obtaining a high quality, multiphase, cross-sectional abdominal imaging to optimally characterize/stage the renal mass. Based on the presence or absence of fat on the CT scan, Dr. Pedrosa provides the following diagnostic algorithm:
Dr. Pedrosa highlighted that ~20% of T1a (<4 cm) resections are benign, with an 82% increase in surgery for benign disease between 2000-2009. Partial nephrectomy is associated with morbidity (13% of patients having a grade 2-3 complication rate) and rare mortality (0.1%), in addition to nephron loss is associated with increased cardiovascular events and decreased survival. The cost of benign nephrectomies in the US in 2014 was estimated to be $153 million/year ($55,573/individual). As such, benign partial nephrectomies are associated with significant patient burden and health care costs.
There are certainly pros and cons associated with biopsying renal masses, as emphasized by Dr. Pedrosa. Pros of renal mass biopsy include it leading to a definitive diagnosis (sensitivity of 97.5%, specificity of 97.2%, and PPV of 99.8%) and reducing the number of benign nephrectomies. Cons of renal mass biopsy include: (i) it is invasive (patients do not like it, it may have complications such as hemorrhage, pain, and hematuria, as well as increased cost) and (ii) diagnostic performance can be an issue in that it may not be feasible or it may not be able to be performed and/or it may be non-diagnostic. Importantly, 37% of benign biopsies represent malignant disease.
Multiparametric mpMRI may be able to assist in predicting pathology of small renal masses. In a single institution study of 103 patients and 109 small renal masses, Kay et al.2 found that clear cell RCC and papillary RCC were diagnosed, with sensitivities of 85% (47 of 55) and 80% (20 of 25), respectively, and specificities of 76% (41 of 54) and 94% (79 of 84), respectively. Inter-reader agreement was moderate to substantial (clear cell RCC, κ = 0.58; papillary RCC, κ = 0.73). Signal intensity of the lesion on T2-weighted MR images and degree of contrast enhancement during the corticomedullary phase were independent predictors of clear cell RCC (signal intensity OR 3.19, 95% CI 1.4-7.1; contrast enhancement OR 4.45, 95% CI 1.8-10.8) and papillary RCC (contrast enhancement OR 0.053, 95% CI 0.02-0.2), and both had substantial inter-reader agreement (signal intensity, κ = 0.69; contrast enhancement, κ = 0.71). Poorer performance was observed for chromophobe histology, oncocytomas, and minimal fat angiomyolipomas, (sensitivity range, 14%-67%; specificity range, 97%-99%), with fair to moderate inter-reader agreement (κ range = 0.23-0.43). A summary of the results are as follows:
Among small-renal masses (<= 4 cm), clear cell is the most common histology and also the fastest growing while under surveillance:
Dr. Pedrosa then discussed the clear cell likelihood score v2.0, which assesses likelihood of clear cell RCC based on MRI signal intensity on T2 vs renal cortex, enhancement, and corticomedullary phase intensity. Clear cell likelihood scoring is as follows: 1 – very unlikely, 2 – unlikely, 3 – intermediate risk, 4 – likely, and 5 – very likely:
Work from Dr. Pedrosa’s group prospectively assessed the clear cell likelihood score,3 assessing 57 patients with 63 cT1a renal masses. Mean tumor size was 2.7 ± 0.7 cm and the histology distribution of cohort by clear cell likelihood score is as follows:
Defining clear cell likelihood score 4–5 lesions as positive demonstrated an overall accuracy of 84%, sensitivity of 89%, specificity of 79%, positive predictive value of 84%, and negative predictive value of 86%. A clear cell likelihood score of 1–2 demonstrates an 86% accuracy and 100% sensitivity/positive predictive value of identifying non-clear cell RCC histology:
Dr. Pedrosa notes that for clear cell likelihood score 3, this comprised 11% of all T1a lesions, 57% of which were clear cell RCC, and 43% which were benign. As such, for these specific patients, biopsy has the highest diagnostic yield. In a follow-up study from Dr. Pedrosa’s group,4 they assessed the association of the clear cell likelihood score on MRI with growth rates and progression of small renal masses. Growth rates of 386 small renal masses (100 clear cell likelihood score 1-2, 75 clear cell likelihood score 3, and 211 clear cell likelihood score 4-5) from 339 patients were analyzed. The clear cell likelihood score was also correlated with growth rates by size (clear cell likelihood score 4-5: 9%/year, clear cell likelihood score 1-2: 5%/year, p<.001) and by volume (clear cell likelihood score 4-5: 29%/year, clear cell likelihood score 1-2: 16%/year, p<.001):
Data from the Toronto group led by Finelli et al.5 has assessed small renal mass growth of biopsy-confirmed RCC. Among 136 biopsy-confirmed RCC small renal masses, the median follow-up for patients who remained on active surveillance was 5.8 years (IQR 3.4-7.5 years). Clear cell RCC small renal mass grew faster than papillary type 1 small renal mass (0.25 and 0.02 cm/year on average, respectively, p = 0.0003):
Overall, 60 small renal mass lesions progressed: 49 (82%) by rapid growth (volume doubling), seven (12%) increasing to ≥4 cm, and four (6.7%) by both criteria.
Dr. Pedrosa concluded his presentation of the virtual biopsy for characterizing small renal masses with the following take-home message:
- Up to 20% of small renal masses (<= 4cm) are benign, many ‘malignant’ tumors are indolent, but a substantial number are potentially aggressive
- Percutaneous renal mass biopsy is highly accurate for malignancy, but is not feasible in all patients and is non-diagnostic in up to 20%
- Virtual biopsy with clear cell likelihood score on MRI can assist in the management of small renal masses, by decreasing the need for percutaneous biopsy and decreasing the benign nephrectomy rate
Presented by: Ivan Pedrosa, MD, PhD, Professor of Radiology, Urology and Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the International Kidney Cancer Symposium (IKCS) 2021 Annual Congress, November 5 and 6, 2021.
- Campbell SC, Clark PE, Chang SS, et al. Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-Up: AUA Guideline: Part I. J Urol. 2021 Aug;206(2):199-208.
- Kay FU, Canvasser NE, Xi Y, et al. Diagnostic performance and interreader agreement of a standardized MR imaging approach in the prediction of small renal mass histology. Radiology. 2018 May;287(2):543-553.
- Johnson BA, Kim S, Steinberg RL, et al. Diagnostic performance of prospectively assigned clear cell Likelihood scores (ccLS) in small renal masses at multiparametric magnetic resonance imaging. Urol Oncol. 2019 Dec;37(12):941-946.
- Rasmussen RG, Xi Y, Sibley III R, et al. Association of clear cell likelihood score on MRI and growth kinetics of small solid renal masses on active surveillance. ARJ 2021;
- Finelli A, Cheung DC, Al-Matar A, et al. Small renal mass surveillance: Histology-specific growth rates in a biopsy-characterized cohort. Eur Urol. 2020 Sep;78(3):460-467.