Successful management of retinal metastasis from renal cancer with everolimus in a monophthalmic patient: a case report
Essadi et al. Journal of Medical Case Reports
Successful management of retinal metastasis from renal cancer with everolimus in a monophthalmic patient: a case report
Ismail Essadi 0 1 3
Issam Lalya 0 2 3
Mohamed Kriet 0 3 6
Abdelhamid El Omrani 0 3 5
Rhizlane Belbaraka 0 3 4
Mouna Khouchani 0 3 5
0 Cadi Ayad University , Marrakesh , Morocco
1 Medical Oncology, Ibn Sina Military Hospital, Cadi Ayad University , Marrakesh , Morocco
2 Radiation Oncology, Mohamed V Military Hospital
3 Rabat , Morocco
4 Medical Oncology, Mohamed VI University Hospital, Cadi Ayad University , Marrakesh , Morocco
5 Radiation Oncology, Mohamed VI University Hospital, Cadi Ayad University , Marrakesh , Morocco
6 Ophthalmology, Ibn Sina Military Hospital, Cadi Ayad University , Marrakesh , Morocco
Background: The retina is an uncommon site for metastases, in particular from solid tumors. Some authors have reported a recent increase in the incidence of metastases in infrequent sites, such as brain or bone, probably due to the expanded treatment options and the resulting improved survival. Choroidal metastasis is the most common type of intraocular malignancy. The most common primary sites associated with choroidal metastasis are breast cancer in women and lung cancer in men. Treatment options are limited, but they must be discussed and adapted to the patient profile. Cases presentation: We report a case of a 62-year-old Moroccan man with a history of monophthalmitis secondary to a war injury of 30 years' duration. He has been followed for 28 months for metastatic clear-cell renal carcinoma. The firstline treatment was effective for 24 months, before disease progression as retinal metastasis and accentuation of lung metastases. A second-line treatment with everolimus resulted in marked improvement of symptoms, complete recovery of visual function, and partial response in retinal localization. Conclusions: Choroidal metastasis of renal cancer is a rare situation that must be actively sought in order to arrive at a suitable therapeutic approach.
Retina; Metastasis; Clear cell carcinoma; Kidney
The occurrence of retinal metastasis is a rare presenting
manifestation of solid tumors [
]. Metastatic tumors are
the most common intraocular malignancy in adults [
They are most commonly found in the choroid and less
frequently in the iris and ciliary body [
]. Owing to its high
vascularity, the posterior choroid is particularly exposed to
blood-borne cancer cells [
]. Although symptomatic
choroidal metastasis is less common than asymptomatic
choroidal metastasis, visual disturbance caused by cancer
metastasis from other organs is one of the most important
limits on the quality of life of patients with cancer [
Therefore, further improvement of the therapy for visual
disturbance is needed. Clinically available therapies for
choroidal metastasis are currently very limited [
Chemotherapy causes systemic adverse effects and is not
always effective. Radiotherapy provides local therapy but
has several complications, including cataract, exposure
keratopathy, iris neovascularization, radiation retinopathy,
and radiation papillopathy [
]. We report a case of a
patient successfully managed with everolimus as second-line
treatment of retinal metastasis from renal cancer.
A 62-year-old Moroccan man presented to our hospital
with a history of monophthalmitis secondary to a war
injury sustained 30 years earlier. He had been followed
for 28 months for metastatic clear cell renal carcinoma
(Fig. 1). The secondary sites were represented by
bilateral pulmonary nodules (Fig. 2). The first-line treatment
with sunitinib 50 mg per day (4 weeks on, 2 weeks off )
was effective for 24 months and well tolerated. Clinical
evaluation demonstrated a large visual field. An
ophthalmological assessment with angiography showed the
presence of a retinal tissue process (Fig. 3). A cerebral
scan confirmed the presence of a retinal metastatic
lesion without any cerebral localization (Fig. 4). The rest
of the extension report was in favor of an increase in the
number and size of pulmonary lesions.
A second-line treatment based on everolimus 10 mg
daily was started. Evaluation after 4 months revealed
marked improvement of symptoms and complete
recovery of visual function, despite the persistence of
imaging-detected retinal metastasis that was significantly
decreased in size (Fig. 5). The use of everolimus was
associated with the occurrence of grade 2 mucositis, which
rapidly resolved after symptomatic treatment.
Retinal metastases are unusual complications of
]. Nevertheless, some authors have reported a
recent increase in the incidence of metastases in
infrequent sites, such as brain or bone, probably due to the
expanded treatment options and the resulting improved
The most common intraocular tumor is choroidal
metastasis from lung cancer in men and breast cancer in women
]. In the absence of specific series in the literature, the
incidence of renal cancer metastasizing to the retina is
certainly even lower than to other sites [
]. The prognosis of
choroidal metastasis depends on its primary site [
The diagnosis is suspected on the basis of the
appearance of visual disturbances and the presence of significant
eye pain in a patient followed for cancer [
]. It is
confirmed by retinal angiography, which shows nodular
]. Some imaging methods, such as magnetic
resonance imaging (MRI) or computed tomography, can
individualize a retinal process [
]. Fine-needle aspiration
biopsy may be indicated in some situations, such as uveal
metastasis without known primary tumor and patients
requesting histopathological confirmation before
undergoing recommended therapy such as enucleation . Our
patient could not benefit from an MRI, owing to the
foreign body persisting within the left orbit since his war
injury, which had caused the loss of his left eye 30 years ago.
He was followed for evolutionary kidney cancer and did
not require histological confirmation. Treatment options
include observation if the patient is preterminal or the
metastasis appears regressed; systemic therapy
(immunotherapy, targeted therapy) or whole-eye radiotherapy if the
metastases are multifocal, bilateral, or associated with
extensive subretinal fluid; plaque radiotherapy for solitary
metastasis; and enucleation, which is considered in very
limited cases such as choroidal metastasis that is
progressive and causes refractory pain [
Until recently, metastatic renal cell carcinoma was
considered a cancer with a poor prognosis. Treatment options
were limited to cytokines (interferon, interleukin 2). Recent
years have been marked by the recognition of several small
molecules in metastatic renal cancer [
(RAD001) is an orally administered inhibitor of the
mammalian target of rapamycin, a component of an
intracellular signaling pathway that regulates cellular
metabolism, growth, proliferation, and angiogenesis [
Everolimus has become individualized as a serious option
after failure of antiangiogenic therapy . Investigators in
the RECORD-1 phase III trial compared everolimus with
placebo in patients with metastatic renal cell carcinoma
that had progressed while they were receiving sunitinib,
sorafenib, or both [
]. Median progression-free survival
(PFS) was significantly better in the everolimus arm (4.9 vs.
1.9 months; HR 0.33; P < 0.001), and 21% of patients had
previously received one systemic treatment option. Median
overall survival (OS) was similar between the two groups
(HR 0.90; 95% CI 0.71–1.14). The most common grade 3/4
adverse events in the everolimus arm were asthenia,
stomatitis, pneumonitis, dyspnea, infections, fatigue,
dehydration, and abdominal pain [
]. Updated analysis
showed median OS of 14.8 months in the everolimus arm
vs. 14.4 months in the control group (HR 0.87; P = 0.162);
however, preplanned crossover occurred in 79.9% of
patients and probably confounded the survival benefit. Only
1% of patients in that study achieved a partial objective
]. Our patient had a clear partial response
estimated to be 50% with a good tolerance of everolimus.
Although the benefits of everolimus may need to be
evaluated in clinical trials, this may not be feasible, owing to the
rarity of the choroidal metastasis of clear cell renal cancer.
Nivolumab is a humanized antibody against
programmed cell death protein 1 receptor. Researchers in a
pivotal trial (CheckMate 025) enrolled 821 previously
treated patients and randomized them to a nivolumab arm
(3 mg/kg every 2 weeks) or an everolimus arm (10 mg
daily). The primary endpoint of their study was OS.
Nivolumab significantly improved median OS (25.0 vs.
19.6 months; HR 0.73; 95% CI 0.60–0.89; P = 0.0018). The
overall response rate was better with nivolumab (25% vs.
5%), whereas there were no difference in the median PFS
(4.6 vs. 4.4 months) [
Cabozantinib is a multikinase inhibitor targeting vascular
endothelial growth factor receptor, MET, RET, and AXL.
These tyrosine kinases are involved in oncogenesis,
metastasis, tumor angiogenesis, and drug resistance. METEOR
was a phase III study in which researchers randomized 658
previously treated patients to cabozantinib 60 mg daily or
to everolimus 10 mg daily. Median PFS (the primary
endpoint of the study) was significantly better with
cabozantinib (7.4 vs. 3.8 months; HR 0.58; 95% CI 0.45–0.74; P <
0.0001). The response rate was also better with
cabozantinib (21% vs. 5%) [
]. Both nivolumab and cabozantinib are
still not available in Morocco.
We present a case of a patient followed for metastatic
clear cell renal cancer who had a large retinal mass on
one eye that appeared while under treatment. This
metastatic event is very rare. This case highlights the
possibility of successful management of retinal metastasis by
medical means. Thus, only a greater awareness of the
problem will lead to choosing the best therapeutic
approach to individual patients.
We sincerely thank Souad Tadlaoui for her assistance.
Availability of data and materials
Not applicable to this report, because no datasets were generated or
analyzed during the present study.
All authors read and approved the final manuscript.
Ethics approval and consent to participate
Consent for publication
Written informed consent was obtained from the patient for publication of
this case report and any accompanying images. A copy of the written
consent is available for review by the Editor-in-Chief of this journal.
The authors declare that they have no competing interests.
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