ASCO GU 2018: The Importance of Tumor Heterogeneity for the Interpretation of Renal Mass Biopsy
Current guideline recommendations
1. AUA renal mass and localized renal cancer guidelines 20171 – have now included RTB as part of the guidelines
- Should be considered when a mass is considered to be non-malignant (hematologic, inflammatory, infectious)
- Beyond that, should be obtained on a utility-based approach
- RTB not required for young healthy patients who are unwilling to accept uncertainties OR older, frail patients who will be managed conservatively regardless
- When considering RTB, patients should be counseled re: rationale, risks/benefits
- No risk of seeding in contemporary literature
- Safe (<5% risks)
- Statistics: 98% sensitivity, 96% specificity, 99.8% PPV, non-diagnostic rate on initial biopsy ~14%, histologic RCC subtype is very accurate, but * non-malignancy biopsy rate (NPV) may not truly indicate benign entity
2. ASCO guidelines2
- All patients with small renal mass (SRM) should be considered for RTB if it will change management
- Patients undergoing AS should be considered for RTB – but not all patients need it
- Patients considering ablation should have pre-ablation biopsy
- Similar diagnostic yields as the AUA guidelines
- Tumor heterogeneity is a challenge with RTB – in terms of morphology, grade, histology
Tumor Heterogeneity in SRMs
Ball et al3 demonstrated that in 32 patients with cT1a tumors, there was heterogeneity in 81% of samples and 31% of samples were discordant. 5 median slides taken from each tumor. Multiple grades were present from samples from the same tumor.
Ito K et al4 demonstrated that even when higher grade disease is present in small volumes, clinical outcomes are similar to patients with predominant higher grade disease. Hence, tumor heterogeneity matters – missed high grade disease can drive clinical outcomes.
Histology clearly has an impact on outcomes. It is relatively well established that some histologic subtypes (ie Papillary Type 1 or chromophobe) are more indolent than their clear-cell RCC counterparts. This has been demonstrated in surveillance and focal ablation series.
Therefore, he posed the question, does the number of cores from a RTB matter? Does that help improve diagnostic yield? Hobbs et al5 helped address this in their prospective ex vivo study and found that increasing from 1 to 2 to 3 cores increased diagnostic yield for histology from 44% to 67%, but only increase yield for grade from 27% to 39%.
Can imaging help improve diagnostic yield? A recent study by Oh et al6 demonstrated that apparent diffusion coefficient (ADC) in a diffusion weight MRI was able to distinguish high grade from low grade RCC; high-grade RCC had a much lower ADC. Predictive accuracy was 70.5%. Based on this and other study, he suggested we start to take guidance from prostate fusion biopsy technology to introduce fusion technology for renal mass biopsies.
Conclusions:
1. Current biopsy technique – accurate for histology, less so for grade
2. Heterogeneity with respect to grade can confound ability of biopsy to predict outcomes and guide management.
3. Biopsy matters! Grade and Histology affect ablation success
4. Time to consider changing practice – biopsy to risk stratify: prior to AND in a separate setting from ablation
5. Consider increasing the number of cores to 3+ to increase diagnostic yield for grade
6. The future: fusion technology/targeted biopsy to identify aggressive areas of tumor or areas of high-grade disease
Presented by: Ithaar Derweesh, MD University of California, San Diego
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto | @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
References:
1. Campbell S, Uzzo RG, Allaf ME, Bass EB, Cadeddu JA, Chang A, Clark PE, Davis BJ, Derweesh IH, Giambarresi L, Gervais DA, Hu SL, Lane BR, Leibovich BC, Pierorazio PM. Renal Mass and Localized Renal Cancer: AUA Guideline. J Urol. 2017 Sep;198(3):520-529. doi: 10.1016/j.juro.2017.04.100. Epub 2017 May 4.
2. Finelli A, Ismaila N, Bro B, Durack J, Eggener S, Evans A, Gill I, Graham D, Huang W, Jewett MA, Latcha S, Lowrance W, Rosner M, Shayegan B, Thompson RH, Uzzo R, Russo P. Management of Small Renal Masses: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2017 Feb 20;35(6):668-680. doi: 10.1200/JCO.2016.69.9645. Epub 2017 Jan 17.
3. Ball MW, et al. Grade heterogeneity in small renal masses: potential implications for renal mass biopsy. J Urol. 2015 Jan;193(1):36-40. doi: 10.1016/j.juro.2014.06.067. Epub 2014 Jun 21.
4. Ito K, Yoshii H, Asakuma J, Sato A, Horiguchi A, Sumitomo M, Hayakawa M, Asano T. Clinical impact of the presence of the worst nucleolar grade in renal cell carcinoma specimens. Jpn J Clin Oncol. 2009 Sep;39(9):588-94. doi: 10.1093/jjco/hyp068. Epub 2009 Jun 25.
5. Hobbs DJ, Zhou M, Campbell SC, Aydin H, Weight CJ, Lane BR. The impact of location and number of cores on the diagnostic accuracy of renal mass biopsy: an ex vivo study. World J Urol. 2013 Oct;31(5):1159-64. doi: 10.1007/s00345-012-0868-3. Epub 2012 Apr 15.
6. Oh S et al. Correlation of CT imaging features and tumor size with Fuhrman grade of clear cell renal cell carcinoma. Acta Radiol. 2017 Mar;58(3):376-384. doi: 10.1177/0284185116649795. Epub 2016 Jul 19.