Late Relapsing Renal Cell Carcinoma:
A Brief Review Suggests Expected PFS and
OS 5 Years and Beyond after Nephrectomy
Introduction
In the past decade, the treatment of renal cell carcinoma
(RCC) has advanced more rapidly than at any other time
in medical history. Better imaging techniques have led to
increased detection of small, localized lesions, leading to
higher rates of resection with curative intent.1 Partial
nephrectomies and other nephron-sparing approaches
have also been refined. And, of course, major advancements
in systemic therapies including the development
of oral targeted therapies and immune checkpoint inhibitors
have led to unprecedented improvements in outcomes
for patients with advanced, unresectable disease.
However, despite these advances, of those patients who
undergo resection of RCC with curative intent, approximately
30% still recur with most of those developing distant
metastatic disease.2 Adjuvant therapy to prevent
such recurrence is still largely under investigation with
many negative trials to date. Only sunitinib has recently
been approved for adjuvant use, and is generally recommended
for selected patients at higher risk of recurrence.
Most post-surgical relapses of RCC occur within 2
years of resection. Rapid recurrence, especially within one
year of definitive surgery, is associated with poorer prognosis
and more aggressive disease. The widely used
Motzer/MSKCC risk stratification model3 uses recurrence
within a year as one of its elements used to categorize risk,
as does the Heng criteria4 and other risk stratification
models. So, if early recurrence is associated with poorer
outcomes, is later recurrence associated with better outcomes?
Late Relapse - Beyond Five Years
Adamy and colleagues analyzed characteristics in patients
with recurrent RCC 5 years or later after nephrectomy to
determine predictors of survival after recurrence. They
analyzed a total of 2,368 nephrectomy cases and found
26 Kidney Cancer Journal
that 256 patients had disease recurrence, and 44 of those
had their disease relapse 5 years or more after nephrectomy.
They found that patients with late recurrence originally
had fewer symptoms at initial presentation, smaller
primary tumors (median 8.5 vs 7 cm) and less aggressive
disease (pT1 in 18% vs 39%). Median overall survival
from the time of recurrence was 6.1 years. A multi-variant
analysis found that longer survival was associated with a
favorable Motzer/MSKCC risk score and the absence of
symptoms related to metastasis.5
Our group conducted a retrospective study to access
outcomes in patients with recurrence >5 years after definitive
nephrectomy. We retrospectively reviewed clinical
data on consecutive patients treated with targeted
therapy for mRCC who were diagnosed >5 years after
nephrectomy with curative intent between November 1,
2006, and November 1, 2013. Patients with a history of
either radical or partial nephrectomy were included. Patients
were excluded if they had evidence of metastases at
the time of surgery or at any time prior to five years beyond
surgery. Of the 520 patients with stage I-III RCC
who underwent definitive complete or partial nephrectomies,
28 were found to have relapsed beyond 5 years,
with a median time between nephrectomy and recurrence
of 8.3 years. Most were categorized as favorable risk
(71%) with only 1 patient having poor risk features, and
all had clear cell histology. Most (83%) presented with
multiple sites of metastases, with lung being the most
common (79%) and bone and pancreases as second most
common (both 33%). We also noted a high number of
unusual sites of metastases including bowel, pleura, muscle,
and abdominal wall, a phenomenon that has been
reported in other studies of late relapsing RCC and in several
case reports.6,7,8
The estimated median overall survival time in our patients
was 60.5 months after detection of metastatic disease,
and the 3-year overall survival rate after detection of
metastatic disease was 71.78% (95% CI, 47.98%-84.77%).
This is similar to that reported in Adamy’s finding and
other analyses. All of our patients were treated with targeted
therapy, with median time to treatment failure on
first-line therapy of 19.7 months (range, 0.5- 41.6). We
Marc R. Matrana, MD, MS, FACP
Director, Precision Cancer
Therapies Program
Ochsner Cancer Institute
New Orleans, Louisiana
Keywords: Late relapsing renal cell carcinoma, recurrence of kidney cancer
more than 5 years following nephrectomy, targeted therapy.
Corresponding Author: Dr. Marc R. Matrana, Third Floor, Benson Cancer
Center, 1514 Jefferson Highway, New Orleans, LA 70121, E-mail: MaMatrana@
ochsner.org
/ochsner.org