May 2019

Partial nephrectomy vs cryoablation for T1a renal cell carcinoma: A comparison of survival benefit stratified by tumour size

Liao X, Qiu S, Wang W, et al.
Cancer Epidemiology. April 2019.
DOI: 10.1016/j.canep.2019.02.016

Abstract

OBJECTIVES:

We compared the impact on survival outcomes of partial nephrectomy (PN) and cryoablation (CA) for patients diagnosed with T1a renal cell carcinoma (RCC).

PATIENTS AND METHODS:

Among patients diagnosed between 2004 and 2014 in the Surveillance, Epidemiology and End Results program, we identified histologically confirmed T1aN0M0 RCC treated with PN (n = 17644) or CA (n = 868). Propensity score matching (PSM) was performed. Kaplan-Meier method, Cox proportional hazards model were used to calculate cancer specific mortality (CSM) and overall mortality (OM) in the unmatched and matched cohort, and in subgroups based on tumour size (< 2 cm, 2-3 cm, 3-4 cm). Sensitivity analyses were performed.

RESULTS:

A total of 18512 patients were identified: PN (93.88%) and CA (6.12%). In the propensity-score matched cohort, for tumours ≤ 2 cm, the CA and PN groups had similar CSM (HR: 1.41, 95% CI: 0.32–6.31, p = 0.65) and OM (HR 0.97, 95%CI: 0.47–2.01, p = 0.93). For tumours 2-3 cm, CA was associated with similar CSM (HR 1.64, 95%CI: 0.67–4.03, p = 0.28) but higher OM (HR 2.05, 95%CI: 1.35–3.11, p < 0.001), compared with PN. For tumours 3-4 cm, CA was associated with increased CSM (HR: 3.76, 95% CI: 1.62–8.69, p = 0.002) and OM (HR 2.17, 95%CI: 1.48–3.18, p < 0.001).

CONCLUSIONS:

For RCC ≤ 2 cm, PN and CA are equal in survival outcomes. For RCC 2-4 cm, PN may have a possible advantage over CA.

Read article

Conditional survival of patients with small renal masses undergoing active surveillance

Petros F, Venkatesan A, Kaya D, et al.
BJUI. March 2019.
DOI: 10.1111/bju.14486

Abstract

OBJECTIVES:

To determine conditional survival for patients with small renal masses (SRMs) undergoing active surveillance (AS).

MATERIALS AND METHODS:

Patients were enrolled in a prospective AS protocol at our institution between May 2005 and January 2016. Patients with SRMs ≤4 cm with serial cross-sectional imaging available in-house for review were included. Overall survival (OS) was estimated using the Kaplan–Meier method and modelled via Cox proportional hazards models. The primary endpoints analysed were the conditional probability of survival and tumour growth over time. Landmark analysis was used to evaluate survival outcomes beyond the 2-year mark after the initial scan. The relative conditional survival of patients on AS was compared to those undergoing partial nephrectomy (PN) using inverse probability of treatment weighting.

RESULTS:

A total of 272 patients were included in this analysis. The mean initial SRM size was 1.74 ± 0.77 cm, and the mean mass size closest to the 2-year mark was 1.97 ± 0.83 cm. The likelihood of continued survival to 5 years improved after the 2-year landmark. Patients with masses <3 cm who survived the first 2 years on AS had a 0.84–0.85 chance of surviving to 5 years, and if they survived 3 years, the probability of surviving to 5 years improved to 0.91. A slow tumour growth (β: 0.12; P < 0.001) with parallel growth rates was found for tumours <3 cm. Patients on AS and those who underwent PN had similar OS for ~7 years, beyond which PN demonstrated a trend of lower risk of death compared with AS (hazard ratio 0.57; P = 0.07).

CONCLUSIONS:

The conditional survival probability of patients with SRMs <3 cm on AS increased after 2 years. This information may prove useful to urologists and patients who are considering continuing AS vs intervention after the first 2 years on AS.

Read article

Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohortstudy

Martínez Chanzá N, Xie W, Asim Bilen M, et al.
Lancet Oncol. 2019 Feb 28
DOI: 10.1016/S1470-2045(18)30907-0

Abstract

BACKGROUND:

An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB.

METHODS:

We did a multicentre, international, retrospective cohort study of patients with metastatic non-clear-cell renal cell carcinomatreated with oral cabozantinib during any treatment line at 22 centres: 21 in the USA and one in Belgium. Eligibility required patients with histologically confirmed non-clear-cell renal cell carcinoma who received cabozantinib for metastatic disease during any treatment line roughly between 2015 and 2018. Mixed tumours with a clear-cell histology component were excluded. No other restrictive inclusion criteria were applied. Data were obtained from retrospective chart review by investigators at each institution. Demographic, surgical, pathological, and systemic therapy data were captured with uniform database templates to ensure consistent data collection. The main objectives were to estimate the proportion of patients who achieved an objective response, time to treatment failure, and overall survival after treatment.

FINDINGS:

Of 112 identified patients with non-clear-cell renal cell carcinoma treated at the participating centres, 66 (59%) had papillary histology, 17 (15%) had Xp11.2 translocation histology, 15 (13%) had unclassified histology, ten (9%) had chromophobe histology, and four (4%) had collecting duct histology. The proportion of patients who achieved an objective response across all histologies was 30 (27%, 95% CI 19-36) of 112 patients. At a median follow-up of 11 months (IQR 6-18), median time to treatment failure was 6·7 months (95% CI 5·5-8·6), median progression-free survival was 7·0 months (5·7-9·0), and median overall survival was 12·0 months (9·2-17·0). The most common adverse events of any grade were fatigue (58 [52%]), and diarrhoea (38 [34%]). The most common grade 3 events were skin toxicity (rash and palmar-plantar erythrodysesthesia; five [4%]) and hypertension (four [4%]). No treatment-related deaths were observed. Across 54 patients with available next-generation sequencing data, the most frequently altered somatic genes were CDKN2A (12 [22%]) and MET (11 [20%]) with responses seen irrespective of mutational status.

INTERPRETATION:

While we await results from prospective studies, this real-world study provides evidence supporting the antitumour activity and safety of cabozantinib across non-clear-cell renal cell carcinomas. Continued support of international collaborations and prospective ongoing studies targeting non-clear-cell renal cell carcinoma subtypes and specific molecular alterations are warranted to improve outcomes across these rare diseases with few evidence-based treatment options.

Read article

State of the Future: Translational Approaches in Renal Cell Carcinoma in the Immunotherapy Era

Bakouny Z, Flippot R, Braun DA, et al.
Eur Urol Focus. 2019 Feb 28.
DOI: 10.1016/j.euf.2019.02.014

Abstract

The emergence of immune checkpoint inhibitors as treatment options for metastatic renal cell carcinoma (RCC) has significantly improved outcomes for patients, but also posed new challenges for researchers. Only a subset of patients respond to these therapies, and some who initially respond ultimately develop therapeutic resistance. In this brief report, we review and discuss the importance of novel technological advances for immunotherapy translational research in RCC. In particular, we highlight the potential of single-cellsequencing methods and novel PD-L1 tracer-based imaging modalities for biomarker discovery, as well as ex vivo tumor spheroids for the creation of tumor “immunograms”.

PATIENT SUMMARY:

Immunotherapy, which leverages a patient’s immune system to target tumors, is effective for a substantial number of patients with metastatic kidney cancer. We review novel technologies that may help in understanding why some patients do not respond to these treatments, with the goals of eventually being able to identify which patients will respond to therapy and developing strategies to overcome therapeutic resistance.

Read article
You don't have permission to register