Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias.
To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence.
Design, setting, and participants
RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively.
Local treatment of recurrence.
Outcome measurements and statistical analysis
Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups.
Results and limitations
Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40–80] vs 69.2 [45–87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58–82.6) versus 27.4 mo (95% CI 23.6–31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2–0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20–0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02–3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2–0.64), 0.27 (0.11–0.65), and 0.26 (0.08–0.8), respectively. Limitations include retrospective design.
This is the first study assessing the effectiveness of LTR in RCC in a comparable population with RD. This study supports the role of LTR across all RoR groups.
The current publication (Marconi et al) belongs to a retrospective multi-institutional kidney cancer registry (RECUR) that includes patients between 2006 and 2011 (TKI era) with long-term follow-up. Patients were stratified in 2 groups; those who received local treatment of recurrence (LTR) (n=97) and non-LTR (n=79). The authors defined recurrent disease as presence of solitary metastasis, oligometastatic disease up to 3 metastasis in one organ and local renal fossa recurrence. The primary endpoint of the study was to characterise overall survival according to baseline risk of recurrence after LTR. Over 90% of recurrence were treated with metastasectomy. Aiming to mitigate the inherent biases (such as relapse volume) from those retrospective registries, the comparison between groups showed a persistent advantage of patients receiving LTR in those subgroups with low-volume, translating into a 63% reduction (HR 0.37) of risk of death in those patients receiving LTR. Patients in the non-LTR group had high-risk features at nephrectomy (58% vs 37%); more abdominal recurrences (46 % vs 27%), shorter time to recurrence (24 mo vs 31 mo) and larger tumours at diagnosis (cT1a 10% vs 24%). As we can expected from those differences, a surgical case selection towards “good players” is observed in the LTR group.
Reports on optimal approach for low-volume recurrences after nephrectomy has consistently been flawed by retrospective analysis on surgical databases demonstrating survival advantages for complete resection of disease. However, this is the largest dataset of its kind. Several questions need to be considered when analysing the current data, such as, how safe is complex surgery of a recurrent disease? Surgical complications associated with resections were not reported in the current study. Also, what is the percent role of successive lines of systemic treatment over complete resection? Current data on the immunotherapy era with prolonged survival and better response rates is suggesting the role of surgery on residual disease; would that improve the selection criteria for optimal candidates to local resection. Moreover, SBRT will be presented at EAU23 on its primary outcomes of a phase II prospective randomised trial for treatment of primary RCC on patients unsuitable for surgery. Could that also replace surgery on the LTR disease state? Longer follow-up will help elucidate if it is a feasible option also for metastatic sites treatment and these trials with current systemic treatment and sequencing are ongoing. The optimal treatment sequence at recurrence requires further investigation as integration of systemic therapies might determine final survival for those patients.
In summary, optimal candidates for LTR remains to be elucidate and should be discussed as part of a multidisciplinary approach.