Treatment of early-stage RCC: observation

Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)

Growth rates

Overdiagnosis of malignancy, along with receipt of unneeded treatment as well as its attendant risks, is arguably the most important harm associated with early cancer detection. Recent attention has been directed toward describing the natural history, or growth kinetics, of localized RCC under observation in an effort to identify which lesions are safe to observe and which require early definitive intervention. In an attempt to consolidate these individual small experiences and identify growth trends in SRMs, Chawla et al. performed a meta-analysis of nine singleinstitution retrospective series including 234 masses followed for a mean duration of 34 months. Initial tumor diameter was 2.6 cm, mean growth rate was 0.28 cm/year, and pathologic confirmation was available in 46% (92% RCC or RCC variant) [14]. We have recently updated these findings in a pooled analysis of 259 patients (284 masses) with available individual level data [29]. This analysis revealed a mean age of 66.9 years, a mean initial tumor size of 2.4 cm, and mean final tumor size of 3.2 cm. With a mean duration of observation of 33.6 months, the calculated mean change in maximal diameter per year (linear growth rate) was 0.33 cm/year. These data confirm initial observations that a majority of localized renal tumors exhibit slow radiographic growth with low metastatic potential while under an initial period of observation.

Although growth kinetics of small renal masses were initially studied in cT1a masses, there now exists an emerging literature examining growth rates of cT1b and cT2 tumors that have been followed with active surveillance. In this recently published study with 39 months of follow-up, the mean linear growth rate was 0.44 cm/year, and 66% of these patients continued with AS while 34% progressed to definitive intervention [92]. Specifically, tumors that were continued on AS had a growth rate of 0.37 cm/ year, while masses that underwent definitive surgical management grew at 0.73 cm/year [92]. Importantly, no patients in this study developed metastatic disease after AS. This study appears to suggest that the growth kinetics of even larger renal masses are predictable and may safely be monitored using an active surveillance protocol [92].

Progression rates

Progression to metastatic disease in patients with localized RCC or SRMs under AS is uncommon and poorly documented in the literature. Our recent systematic review identified 18 patients progressing to metastatic disease from a cohort of 880 patients with SRMs under AS (a total of 2.1%) [29]. Comparing patients that progressed to metastatic disease in our systematic review (n = 18) with those that did not in our pooled cohort of patients with individual level data (n = 281), the duration of observation was similar between groups (40.2 vs. 33.3 months; p = 0.47), but there were significant differences in mean patient age (75.1 vs. 66.6 years; p = 0.03). Trends in patients progressing to metastases included larger tumor size (4.1 vs. 2.3 cm; p < 0.0001) and estimated tumor volume (66.4 vs. 15.1 cm3; p < 0.0001) at diagnosis as well as mean linear (0.80 vs. 0.30 cm/year; p = 0.0001) and volumetric growth rates (27.1 vs. 6.2 cm3/year; p < 0.0001). Important observations to consider are that metastasis was a late event (>3 years following diagnosis), all lesions that progressed were >3 cm at the time of metastasis, all demonstrated positive growth rates, and no lesion exhibiting zero net growth while under surveillance has developed metastases while under observation.

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