Concurrently, active surveillance (AS) for small renal masses (SRMs) has emerged as an alternative to surgical therapy to minimize the risks of overtreatment in patients with severe competing risks due to co-morbidity. However, due to the limited clinical experience to date, there is poor understanding of the growth patterns and metastatic potential of untreated renal tumors. To further characterize the natural history of SRMs under observation, we conducted a systematic review and pooled analysis of contemporary studies investigating AS with an emphasis on tumor growth kinetics and clinical characteristics of lesions progressing to metastases.
A MEDLINE search was performed to identify all clinical series reporting observation of suspected renal malignancies. We extracted demographic, clinical, and pathologic variables for SRMs progressing to metastases and those who did not. For studies reporting individual level data, comparisons were performed using Wilcoxon rank-sum tests and confirmed when possible using mixed effects linear regressions. A total of 18 series met screening criteria (all ≤level III evidence), of which individual level data was available for pooled analysis in 6 studies.
Eighteen series (880 patients, 936 masses) met screening criteria from which 18 patients progressing to metastasis (2%) were identified (mean 40.2 months). Six studies (259 patients, 284 masses) provided individual level data for pooled analysis. With a mean follow up of 33.5, the mean initial tumor diameter was 2.3 cm and mean linear growth rate was 0.31cm/year. 65 masses (23%) exhibited zero net growth under surveillance; of which none progressed to metastasis, while 129 (45%) ultimately underwent definitive intervention. Pooled analysis revealed increased age (75.1 vs. 66.6 years, p=0.03), initial tumor diameter (4.1 vs. 2.3 cm, p<0.0001), initial estimated tumor volume (66.3 vs. 15.1 cm3, p<0.0001), linear growth rate (0.8 vs. 0.3 cm/yr, p=0.0001), and volumetric growth rate (27.1vs. 6.2 cm3/yr, p<0.0001) in the progression cohort.
In conclusion, our systematic review and pooled analysis support that the majority of SRMs under radiographic surveillance exhibit slow growth kinetics with a low short term risk of metastatic progression. However, a small proportion of SRMs under surveillance demonstrate evidence of progression, but this is both uncommon (2%) and a delayed event (mean >3 years). While tumors that progressed were larger at diagnosis (all >3cm) and grew at significantly faster rates (0.8 cm/yr), the prediction of their natural growth history cannot be reliably determined by serial radiographic data alone. Utilizing available parameters, lesions that exhibit zero growth over time may represent a population appropriate for prolonged AS while positive growth rates self-select for delayed intervention. Until this emerging clinical experience fully matures and more definitive level I data exists, while it appears that observation of SRMs may be delayed for short periods without negative sequelae in patients with objectified competing risks, AS should not be considered an equivalent alternative to definitive surgical therapy in acceptable operative candidates.
Authored and presented by Marc Smaldone, Alexander Kutikov, Brian Egleston, Daniel Canter, Rosalia Viterbo, David Chen, Richard Greenberg and Robert Uzzo at the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
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