EAU 2018: Dividing Pathologically Upstaged T3a Renal Cell Carcinoma is Associated with Improved Alignment of Outcomes: A call for TMN Revision

Copenhagen, Denmark (UroToday.com) In this abstract, the authors propose updating the current TNM staging to account for pathologic upstaging. Specifically, they focus on patients identified on final pathology to represent pT3a disease (“Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota’s fascia”). They correctly note that there is heterogeneity in outcomes in this patient population.

Interestingly, they propose stratifying patients based on initial clinical stage. They feel that patients upstaged to pT3a from cT1 or cT2 fare better than those who were cT3 to begin with.

In this multi-center retrospective analysis of patients with renal cell carcinoma (cT1-3aN0M0) from 1987-2016, they first compared outcomes of patients found to be pT1, pT2 and pT3a. They then went on to further assess patients within the pT3a category based on presenting clinical stage. Comparison was drawn between pT1, pT2 and the subdivided pT3a group (cT1 → pT3a, cT2→ pT3a, and cT3a → pT3a). Primary outcome was recurrence free survival (RFS). Secondary outcomes was OS.

A total of 2573 patients were analyzed (1267 cT1a, 858 cT1b, 314 cT2a, 134 cT2b, with a mean follow up 68.4 months (5.5 years). The rate of incidental T3a upstaging from cT1-2 was 13.9%. Patients who were upstaged were more likely to have larger tumors (6.7 vs. 4.6 cm), be older, male, higher BMI, diabetic, and have higher RENAL scores (8.7 vs. 7.7).

As can be expected and consistent with prior studies, compared to pT1-2 disease, patients with incidental pT3a upstaging had higher rate of recurrence (7.6% vs. 29.6%, p<0.001) and all-cause mortality at last follow up (15.7% vs. 26.9%, p<0.001). This was primarily driven by cancer-specific mortality – 18.7% vs. 4.5%!

With regards to RFS, when pT3a was subdivided based on presenting clinical stage, they noted a significant difference in RFS. Compared to 5-year RFS of pT1 patients (94.4%), cT1 → pT3a aligned with pT2 (76.6% and 81.2%, p=0.346) while cT2 → pT3a aligned with cT3a → pT3a 47.4% and 44.0%, p=0.815). With regards to OS, a similar alignment was noted for 5 year OS after subdivision, where pT1 was 89.9%, while cT1 → pT3a correlated with pT2 (79.8% and 83.1%, p=0.640) and cT2 → pT3a correlated with cT3a → pT3a 67.0% and 64.2%; p=0.893).

As such, they propose re-assigning patients who are found to be upstaged from cT1 → pT3a as pT2 disease, and patients upstaged from cT2 → pT3a to be kept as pT3 disease.

It is a bit unusual to account for clinical stage in final pathologic staging, but intuitively it makes sense. However, from a practical standpoint, it may complicate the situation.

As this is a retrospective study from 1987-2016, perhaps many of the upstaged patients were from an earlier era, where the pre-operative imaging was insufficient to capture cT3 disease? A prospective study may help better delineate this.

Patients with low (5−8), intermediate (9−11) and high (12−14) scores had 32.8%, 5.2% and 0% frequency of BNGN pathology. Patients with low, intermediate and high scores had 7.7%, 18.6% and 34.9% frequency of HG pathology. ROC analysis revealed an area under the curve of 0.767 for the index score.

The authors report this as an initial scoring system to potentially help risk stratify patients. However, it is a surgically treated series and needs to be validated in an AS cohort and in external cohorts.

Speaker: Zach Hamilton

Co-Author(s): Capitanio U, Pruthi D., Liss M., Bindayi A., Larcher A., Ryan S., Reddy M., Yim K., Bloch A., Field C., Berquist S., Ballon-Landa E., Montorsi F., Derweesh I.

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark