Best of EAU: Immune cell populations have prognostic value in RCC

During the Best of EAU21 abstracts session, Dr Alberto Breda (Autonomous University of Barcelona, Spain) highlighted 6 representative abstracts on renal cancer, including 4 from Italy, his country of origin [1]. Assessment of immune cell populations on nephrectomy specimens was shown to have prognostic value in renal cell carcinoma (RCC). Another study externally validated the guidelines for Von-Hippel Lindau disease (VHL) genetic testing. Furthermore, a study on the oncological outcomes of neoadjuvant target therapy and 3 studies on robot-assisted partial nephrectomy were presented.

As opposed to other tumour types, higher levels of tumour-infiltrating lymphocytes have been associated with worse outcomes on systemic treatment in metastatic RCC. Investigators from Leuven, Belgium, included 143 patients of whom 103 (72.0%) experienced disease recurrence and 67 (46.9%) died of RCC [2]. The aim was to explore the impact of immune and stromal cell populations on disease-free survival (DFS) and cancer-specific survival (CSS).

The results demonstrated that Leibovich score and CD8+ T-cell infiltration were both independently associated with poorer DFS (HR 1.27; P<0.001 and HR 2.36; P<0.001) and CSS (HR 1.36; P<0.001 and HR 2.00; P=0.009).

Transcriptome-based estimation of tumour-infiltrating CD8+ T cells on nephrectomy specimens was associated with worse DFS and CSS in clear cell (cc)RCC patients, independent of the established Leibovich risk score. This data demonstrated that assessment of tumour-infiltrating CD8+ T cells on nephrectomy specimens could be easily implemented to refine prognostic information and guide subsequent disease management.

External validation of the VHL Alliance guidelines

In absence of guidelines for VHL genetic testing, the 2020 VHL Alliance recommendations support selective testing of patients with an aggressive phenotype. A study from Italy externally validated these recommendations in a ccRCC cohort [3].

The results demonstrated that among 2,410 ccRCC patients, 11% had a high risk of VHL. However, only 5% exhibited a positive genetic test (VHL genetic mutation). A VHL clinical phenotype was shown in 9% of ccRCC patients, among those the proportion of genetic counsellor referral was 59%.

In this special population, approximately 1 in 10 ccRCC patients harboured a high risk of VHL. However, genetic counsellor referral was observed in little over half of the patients. The remarkably low proportion of genetic counsellor referral in case of high-risk phenotype urges clinicians to pay special consideration for VHL risk profile after ccRCC diagnosis.

Oncological outcomes of neoadjuvant targeted therapy in patients with localised RCC

The role of neoadjuvant target therapy for localised RCC is not clear. It can be used to reduce tumour volume, simplify surgery, and treat micrometastasis. A prospective study from Ukraine was set up to determine whether pre-surgical target therapy with pazopanib facilitates nephron-sparing surgery and improve oncological outcomes for patients with localised RCC (n=167) [4].

In this prospective, randomised trial, pazopanib (800 mg) was administered for 2 cycles of 8 weeks. Neoadjuvant target therapy led to tumour size decrease up to 11.5 mm on average (from median 61.3 mm to 49.8 mm). Tumour downsizing was observed in the vast majority of cases (n=74, 89.2%), with an average decrease of 20.4%. Tumour downsizing after target therapy led to nephron-sparing surgery in 75 (90.3%) patients compared with 41 (48.8%) in the control group (P=0.01). Five-year overall survival rates were comparable in both groups: 91% in the target therapy group versus 80% in the control group (log-rank P=0.18).

This study demonstrated that the use of neoadjuvant target therapy in patients with localised RCC resulted in a tumour size reduction of ~20% but without impact on overall survival.

IGNITE

Currently, pre-operative 3D reconstruction needs to be manually oriented during laparoscopic surgery. An Italian group investigated a new dedicated software called ‘IGNITE’, which is able to automatically anchor preoperative reconstruction with the endoscopic vision of the real organ [5].

Ten cases were enrolled in this pilot experience. Automatic 3D model overlapping led to a correct identification of the tumour, even in endophytic and posterior cases, without risk of complications or positive surgical margins. These findings suggest that the new evolution of the evaluated augmented reality platform based on computer vision algorithm allows for its application in robot-assisted partial nephrectomy.

Renal function deterioration after robotic partial nephrectomy

Totally endophytic “deep” renal tumours represent one of the most challenging scenarios for the urologist. In a retrospective series of Italian patients with cT1-2 renal tumours who underwent robotic partial nephrectomy, severe renal function deterioration rates were analysed and compared with a selectively collected group of patients with deep renal masses, treated with the same intervention in the same institutions [6].

Based on these findings, deep renal masses must be considered as a separate category of tumours due to their technical complexity. This complexity was regardless of renal score, showing a higher rate of severe renal function deterioration over time. These challenging cases are inevitably exposed to a 2-fold increased risk of developing severe chronic kidney disease (CKD) over time.

Robot-assisted radical nephrectomy plus thrombectomy

Radical nephrectomy with inferior vena cava tumour thrombectomy for RCC represents one of the most challenging urologic surgical procedures. A single tertiary-care centre from Italy reported perioperative and oncologic outcomes of 30 consecutive cases of completely intracorporeal robot-assisted radical nephrectomy with inferior vena cava tumour thrombectomy [7]. Thrombectomy levels were level I in 20%, level II in 30%, and level III in 50%.

There was no need for conversion to open surgery. Perioperative complications Clavien III-V were present in 13% of patients. At a median follow-up of 26.5 months, overall survival was 50%, CSS 43%, locoregional recurrence-free survival (LRFS) 93.3%, and metastasis-free survival (MFS) 43.3%. The current small cohort with limited follow-up and the heterogeneous population including a high rate of adjuvant medical treatment (46.7%) preclude definitive conclusions about the oncologic safety of this procedure.

This data suggests that radical nephrectomy with inferior vena cava tumour thrombectomy appears a feasible and safe procedure for RCC in tertiary referral centres, even in the most advanced indications.

1. Breda A. Best of EAU21: Renal Cancer. EAU21 Virtual, 8–12 July 2021
2. Roussel E. P0549, EAU21 Virtual, 8–12 July 2021.
3. Larcher A. P0636, EAU21 Virtual, 8–12 July 2021.
4. Semko S. P0568, EAU21 Virtual, 8–12 July 2021.
5. Amparore D. V23, EAU21 Virtual, 8–12 July 2021.
6. Tuderti G. P0577, EAU21 Virtual, 8–12 July 2021.
7. Anceschi U. P0625, EAU21 Virtual, 8–12 July 2021.

 

Copyright ©2021 Medicom Medical Publishers



Posted on 31 August 2021