A comprehensive search of Embase, Medline, and Cochrane databases was performed, taking into consideration articles published in English from 2000 to 2017 that included adult patients (age >18 years) diagnosed with a CLRM and enrolled on AS. Of note, pathologic confirmation with a renal tumor biopsy (RTB) was not mandatory for consideration. A total of 28 studies, none of which being a randomized clinical trial, were included in the systematic review. The authors stratified their analysis and presented findings separately for two groups: the first group included manuscripts reporting on CLRMs (cT1 and cT2), and the second group included manuscripts reporting specifically on SRMs (≤4 cm in diameter).
In the CLRM group, overall median tumor size was 3.4 cm, median age was 75 years, and median follow-up time was 36 months; in the SRM group, these were, respectively, 2 cm, 73 years, and 43 months. Rates of metastatic progression were similar in both groups, ranging from 0% to 6% in some series. Cancer-specific mortality ranged between 1-18% in the studies reporting on CLRMs but was consistently low at 1% in the SRM cohort. Other-cause mortality, on the other hand, was higher, ranging between 0-45% in the CLRM group and 1-25% in the SRM group. These findings highlight that patients with SRMs under surveillance are more likely to end up dying from other causes unrelated to RCC. This, in turn, is correlated with the fact that AS is most commonly utilized in elderly and/or comorbid patients for whom primary intervention is not an ideal option. It is important to note that the majority of patients in this systematic review’s cohorts were aged >60 years and their median Charlson Comorbidity Index (CCI) was 2.4.
While SRMs generally grow slowly, linear growth rate (LGR), which is the change in maximum tumor diameter over time and usually expressed in cm/year, is commonly used as an objective parameter for recommending delayed intervention in patients managed by AS. The authors reported that growth rate varied dramatically among published series included in this review. The median LGR was 0.37 cm/year (IQR 0.15–0.7) for CLRMs and 0.22 cm/year (IQR 0.11–0.27) for SRMs. Notably, zero tumor growth ranged from 10% to 44%. The average delayed surgery rate was consistent among the series, with 0–30% reported for the CLRM group and 1-26% reported for the SRM group. Within the subgroup of patients with delayed intervention, the median LGRs were 0.73 cm/year (IQR 0.25–1.35) in the CLRM cohort and 0.62 cm/year (IQR 0.30–0.88) in the SRM series. RCC is identified in up to 90% of pathology reports for patients who undergo delayed intervention, and because increased LGR is known to be the major trigger for intervention, a direct correlation between growth rate and malignant biology is generally assumed. It is important to note, however, that both benign and malignant lesions can grow at similar rates or not at all. Moreover, current data from prospective registries indicate that tumor growth rate predicts intervention but is a poor indicator of malignant biology or metastatic potential. Overall tumor size, on the other hand, has been shown to be the greatest predictor of malignant histology, aggressive pathology, and oncologic outcomes and could, therefore, be a more reliable metric when considering delayed intervention.
The role of RTB in the context of AS remains controversial. The RTB rate ranged between 0% and 38% in the CLRM series and between 2% and 64% in the SRM series. While RTB exhibits excellent positive performance characteristics, its use has been limited by concerns about safety, collection of inadequate tissue for diagnosis, discordance with final pathology, and lack of perceived impact on clinical management. Only a few prospective AS registries currently mandate RTB for enrollment. Recent data demonstrate that RTB is not a requisite for safe AS; nonetheless, it is a safe procedure that can provide valuable information for patients and providers when used appropriately. It is important to keep in mind that AS for SRMs and for small RCCs are very similar but distinct processes; thus, recognition of the context in which data are collected and reported is crucial to understanding the safety and applicability of AS for an individual patient.
Although no randomized clinical data are available, AS appears to be a safe and efficacious initial management strategy for many patients with CLRMs, particularly for patients with SRMs and elderly and/or comorbid patients. Long-term results from ongoing prospective studies will determine the durability of AS for select patients.
Written by: Joseph G. Cheaib, MD, MPH1, Riccardo Autorino, MD, PhD2, Phillip M. Pierorazio, MD1, Maria Carmen Mir, MD, PhD3
1. Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD
2. Division of Urology, Department of Surgery, Virginia Commonwealth University Medical Center, Richmond, VA, USA
3. Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain
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