The latest report on intermediate-term outcomes from
DISSRM (n = 317 on AS) at median follow-up of 2.9 years
(including 203 patients with follow-up of >5 years) indicated
that 5-year and 7-year progression-free survival rates
were 76% and 48%, respectively.14 Approximately onethird
of progressions (n = 20, 30.3%) were elevated linear
growth rates in patients who did not undergo intervention.
The remaining two-thirds were mostly crossover
events from AS to delayed intervention (n = 46, 68.2%);
half of those (n = 24, 52.2%) were clinically indicated,
while the others (n = 22, 47.8%) were elective and mostly
based on patient preference. Almost all the clinically indicated
crossover events (n = 23, 96%) were due to growth
rate >0.5 cm/year.
Given this impact of elevated growth rate, patients
who pursued delayed intervention were expectedly found
to have a significantly greater median growth rate compared
to those who remained on AS (0.38 vs 0.05 cm/year,
p<0.001).15 Similar findings were established in the systematic
review by Mir, et al.; relative to overall median
linear growth rates, higher rates were reported when only
subgroups of patients who underwent delayed intervention
were analyzed (0.73 cm/year (IQR 0.25-1.35) versus
the previously stated 0.37 cm/year in the cT1-2 cohort
and 0.62 cm/year (IQR 0.30-0.88) versus the previously
stated 0.22 cm/year in the cT1a cohort).8 In the analysis
by McIntosh, et al., patients with an elevated growth rate
were significantly more likely to undergo delayed intervention
compared to those with a low or zero growth
rate, but cancer-specific survival persisted at 99% in both
cohorts.9 Therefore, elevated growth rate, as a sole factor,
appears to be the most prominent trigger for progression
and delayed intervention in AS cohorts but may not indicate
true metastatic potential of a SRM.
Oncologic outcomes, namely progression to metastatic
disease and cancer-specific death, do not seem to be
influenced by tumor growth rate. In a systematic review
of SRMs progressing to metastases under AS, the rate of
metastatic progression was significantly low at 2%; a
pooled analysis of the metastatic renal masses showed
that 23% of lesions displayed no evidence of growth.7
Mir, et al. demonstrated in their review that linear growth
rate among patients who experienced progression to
metastatic disease was similar to the overall growth rate
of clinically localized renal masses.
In the DISSRM registry, despite the previously reported
high progression rates resulting mainly from tumor
growth rate >0.5 cm/year, oncologic outcomes remained
excellent; the cancer-specific survival rate at 7 years was
still 100%, and none of the patients (0%) experienced
metastatic progression.14,15 Similarly, the RCCC prospective
experience found no association of SRM growth rate
with any predictors of or progression to metastatic disease.
13,16 Furthermore, as noted earlier, McIntosh, et al.
highlighted that while an elevated growth rate was associated
with delayed intervention, it had no impact on oncologic
outcomes; the 5-year cancer-specific mortality was
1.2% (95% CI: 0.4-2.8%) without any correlation to
growth rate, and only 1 of 99 (1%) patients on AS for
longer than 5 years developed metastases.9
In patients who undergo delayed surgical intervention,
RCC is identified in the majority (up to 90%) of
110 Kidney Cancer Journal
pathology reports.8,15 Because increased linear growth rate
is known to be the major trigger for intervention, a direct
correlation between growth rate and malignant biology
is assumed. While prior retrospective analyses have
demonstrated elevated tumor growth rate as a predictor
of adverse pathologic outcomes, these analyses were inherently
subject to retrospective biases and lacked the rigorous
inclusion criteria and standardized follow-up
protocols of AS programs.17-19
Our recent understanding suggests that both benign
and malignant lesions can grow at similar rates or not at
all, underlining that growth alone is not an indicator of
histology.11,20,21 Among AS patients who underwent percutaneous
renal biopsy in the DISSRM registry, growth
rate was not significantly associated with tumor pathology.
12 Moreover, in those who crossed over to receive delayed
surgical intervention, no difference in the pro-
portion of RCC histology, high-grade disease, or pT3 upstaging
based on growth rate has been found upon
histopathologic analysis.15 We, therefore, believe that an
absolute growth rate threshold might not be a reliable
predictor of malignant potential.
The growth rate of SRMs on AS has been shown to be
variable. This variability was found to be highest within
the first year of follow-up and appeared to dampen with
increasing time.12 The high variability did not seem to reflect
tumor biology and was likely the result of random
measurement error; as there were few available images to
use early in AS for assessing tumor size in a short interval,
mathematical artifacts would have been introduced from
extrapolation to longer times. Most SRMs that demonstrated
elevated growth rates in the first 6 months did not
do so at future interval follow-up or on repeat imaging.12
It is important to note here, however, that patients
who underwent delayed intervention in the DISSRM registry
stayed for a median of 12 months (IQR 5.5-23.6)
only on AS before crossing over15; in other words, 50% of
patients who pursued delayed intervention did so within
the first year of follow-up, and while the decision was
based on personal preferences for some of them (elective
crossovers), a significant proportion of patients actually
crossed over due to an elevated growth rate that was interpreted
in the period of highest variability. Therefore,
when an elevated growth rate is encountered in the first
year of AS, we recommend avoiding reflex intervention,
given the high tumor growth rate variability and the low
metastatic potential of SRMs. We also believe that short
interval repeat imaging and/or renal mass biopsy should
be considered as they could prove helpful in this scenario.
Given our experience thus far with AS, we feel it is
worth rethinking and re-evaluating the importance of
SRM linear growth rate in the context of our current definitions
of progression and triggers for intervention. As
discussed in this review, 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
outcomes10,22,23; we, thus, recommend intervention based
on this metric. Given that most SRMs demonstrate nonlinear
growth, recent data showed that multiple consecutive
positive growth periods were positively associated