9.8-129), 3 year OS rate was 63%. The most common adverse
events to targeted therapies in these patients were
fatigue (88%), anorexia (38%) and diarrhea (50%), with
94% of all AEs reported being grade 1 or 2.15
Based on the above data, although rare, it is clear that
patients are at life-long risk of recurrence after resection
of localized RCC as it is possible for metastases to present
>10 years after resection. Patients in our study had relatively
large metastatic burden and a wide distribution of
metastatic sites, insights that may be useful clinically during
surveillance. Our cohort demonstrated favorable
prognostic features and outcomes when compared to historical
controls.
Carrobio and colleagues examined the records of 554
RCC patients who had a negative follow-up during their
first 10 years following radical or partial nephrectomy.
They found patients 29 (5.2%) patients who experienced
disease progression after 10 years, with median occurrence
in this group occurring at 13.4 years following surgery.
Relapse occurred most commonly in the contralateral
kidney (suggesting possible second primary in
some of these cases), lung, bone, and liver. Relapse was
also seen atypical sites, such as the pancreas and thyroid.
16
Abara et al reported three cases of RCC relapsing more
than 10 years following nephrectomy. All of the patients
had relatively indolent recurrent disease, with two of
them having developed oligometastatic disease and
where rendered no evidence of disease after metastectomy.
The third had stable disease for over four years on
sorafenib.17
Conclusions
Late recurrence of RCC following definitive surgical resection
is a known biologic behavior of RCC. Studies have
characterized patients with late relapse, occurring after a
disease-free interval >5 years or more, in terms of patient
and tumor prognostic features and outcomes. Patients
with late relapse seem to have lower T stage initial
diagnosis, lower Furhman grade tumors, and generally
less aggressive disease. It is certainly not surprising, as patients
with more higher grade features and more aggressive
disease likely recur earlier, leaving most only those
patients with more indolent disease vulnerable to late recurrences.
Outcomes in patients with late relapse generally appear
to be better than those relapsing earlier with longer
survival times and longer response to systemic therapies,
although much more research is needed to draw definitive
conclusions.
The data which do exists suggest that an individualized
approach to adjusting surveillance protocols may be
necessary, perhaps by increasing the length of surveillance
in patients with a higher propensity to relapse after
5 years.
As research in this area evolves, a next rational step
would be to look beyond clinical and pathologic makers
28 Kidney Cancer Journal
that might be associated with late relapsing RCC and explore
associations with genetic and molecular markers.
As next generation sequencing becomes more widespread
and informatics continues to improve, it will be fascinating
to see if patterns emerge that might be able to select
those at higher risk for late recurrence based on mutational
analysis or whole tumor genomic sequencing.
Doing so may allow for more accurate selection of patients
for longer term screening following definitive surgery,
bringing us one step closer to true precision oncology
in this subset of patients.
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