A Patient with Metastatic Clear Cell Renal Carcinoma with Long Term Survival Spanning the Era of Pre-Targeted to Molecular Targeted Treatment

Case Report

Ann Hematol Oncol. 2014;1(2): 1007.

A Patient with Metastatic Clear Cell Renal Carcinoma with Long Term Survival Spanning the Era of Pre-Targeted to Molecular Targeted Treatment

John A Copland1, Jerome Marcus2, Kevin Wu3, Joseph G. Cernigliaro4 and Winston W. Tan5*

1Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, USA

2Spring Drive, Wichita KS

3Department of Pathology and Laboratory Medicine, Mayo Clinic Comprehensive Cancer Center, USA

4Department of Diagnostic Radiology, Mayo Clinic Comprehensive Cancer Center, USA

5Division of Hematology & Oncology, Mayo Clinic, USA

*Corresponding author: Winston Tan, Division of Hematology & Oncology, Mayo Clinic Comprehensive Cancer Center, 4500 San Pablo Road, Jacksonville, Florida, 32224, USA

Received: August 23, 2014; Accepted: October 13, 2014; Published: October 15, 2014


Clear Cell Renal Cell Carcinoma (ccRCC) is the most common subtype of kidney cancer, and has the highest risk of developing metastatic disease. Long term survival with durable response remains uncommon despite numerous FDA approved targeted therapies. We report a patient with metastatic ccRCC who survived for 14 years using a number of evolving approaches spanning the pre-targeted era of immunotherapy to present day molecular targeted treatment. These multimodality approaches that included cytoreductive surgery has led to long term survival and a continued high quality of life.

Keywords: Interleukin 2; Clear cell renal cell carcinoma; Molecular targeted therapy; Quality of life; Pulmonary metastasis


Renal Cell Carcinoma (RCC) is one of the most common solid tumors, responsible for over 13,000 deaths annually with an incidence rate of over 63,000 per year in the United States [1]. The clear cell variant (ccRCC) is the most common subtype of RCC, accounting for an estimated 80% of all patients [2]. The prognosis for patients diagnosed with early stage disease is good, with patients demonstrating approximately 70% cure rate [3]. Regrettably, up to 30% of early stage cases of ccRCC treated surgically will relapse with metastatic disease due to the presence of undetectable micrometastases [4]. In addition, 20-30% of all ccRCC patients present with advanced or metastatic disease upon initial diagnosis [5].

Metastatic ccRCC renders a bleak prognosis, with an estimated 5 year overall survival of less than 10% due to lack of remedial therapies that produce significant disease regression or attenuation of disease progression [6]. Drug resistance is a hallmark of ccRCC and is thought to be a culmination of several intrinsic and acquired tumorigenic properties linked to cancer cell heterogeneity, including a lack of known molecular factors which can be targeted pharmacologically [7-11]. ccRCC does not respond to chemotherapy and radiation therapy, and even with targeted treatments drug resistance develops rapidly [8,12]. Interleukin-2 (IL-2) is the only drug approved today by the Food and Drug Administration (FDA) that provides long-term durable response in metastatic ccRCC patients [13]. However, the majority of patients are not able to take this therapy due to multiple co-morbidities and multiple life-threatening toxicities [14]. Only a small subset of patients demonstrate a complete response (7%) but this subset cannot be accurately identified prior to therapy [15]. It is also apparent that ccRCC tumor cells demonstrate a disposition for increased migratory capacity, likely a major contributing factor to the development of tumor metastasis and disease relapse.

In this case report, we present the strategies that have led to a continued high quality of life for over 14 years in a patient with metastatic ccRCC to multiple anatomical sites. Evolving treatment strategies will be shared in chronological order of management of recurring and new sites of metastases.

Case Report

In September 2000, a very active, athletic 58 year-old male in otherwise excellent health began to have progressive weight loss of 18 pounds, night sweats, anemia, fatigue, indigestion and back pain over a four month period. In January of 2001, Computed Tomography (CT) scan revealed a 12.2 x 12.2 mass in the left upper quadrant originating from the upper pole of the left kidney. There was a caudal and anterior displacement of the left kidney by the mass.

A Nephrectomy of the left kidney was performed January 21, 2001anda diagnosis of ccRCC was made. Pathology revealed an 11 cm tumor that had grown into the vena cava. No lymph node involvement was identified but a 1 cm spot on the lung was noted and initially diagnosed as a granuloma. Gross description showed a massively necrotic tumor, nearly in its entirety, and occupying greater than 90% of the kidney. The tumor extends through the surface and into the perinephric fat. The tumor had the following characteristics: extensive necrosis, marked lymphocytic response and Fuhrman nuclear grade IV. Surgical vascular margins are free of tumor. Tumor extends through the renal capsule and into the adrenal gland. Adjacent kidney parenchyma showed extensive angiolymphatic invasion. Following the surgery, the indigestion and back pain resolved immediately.

In April 2001, a repeat CT of the chest showed multiple noncalcified lung nodules with the largest (1 cm) within the posterior segment of the right upper lobe. Due to the short recurrence interval, a clinical diagnosis of metastatic kidney cancer to the lungs was made. At this visit, a discussion occurred related to treatment options. Three modalities of interleukin 2 (IL-2) administrations were discussed. The option chosen was intermediate subcutaneous treatment of IL-2 self-administered at home.

A therapeutic choice - Immunotherapy

On April 30, 2001, self-injection of s.c. IL-2 was started with eighteen million units (mu) on Monday through Friday of the first week followed by nine mu units on Monday and Tuesday and then eighteen mu units on Wednesday, Thursday and Friday of the next five weeks to make a six-week cycle. Three weeks off between cycles was followed by a CT scan to check progress each time. A total of thirteen cycles was repeated over two and a half years (390 injections). For the last five cycles, the time between cycles was increased to four weeks, then five, then six weeks. The toxicities that the patient experienced included fever (101 – 103C, 2 hours after injection), chills for about 30 – 60 minutes and fatigue. Follow up CT scan (8/21/2001), revealed that lung metastases had shrunk. The greatest reduction in visible metastases was observed between 2nd and 3rd cycles of IL-2. CT of the pelvis was normal. In December, 2001, CT scans demonstrated continued shrinkage of lung metastases. By March 2002 all lesions were stable. In July 2002, a PET scan found no hypermetabolic focus in the lung and patient was declared to be in complete remission.

It should be noted that the same week that IL-2 was started (April 2001), allergy shots(1.2 cc each of ragweed mix 400 PNU/ml mold mix 1-10 w/v and mixed mites 500 AU/ml) were reinitiated at 0.5 cc weekly dose. Initially, allergy shots began as a teenager and continued into the late 30’s.

Discovery of new metastasis and advent of molecular targeted treatment

In June 2007, an abdominal CT scan showed an 8x7x10 cm mass in the peri-colonic area (Figure 1A). In July 2007, a surgical resection was performed that partially removed the colon and gall bladder. Histology confirmed metastatic ccRCC (Figure 1B). In July 23, 2007, IL-2 s.c. therapy was repeated for 3.5 months (11/9/2007) with no CT scan response. During this time, several new small subcentimeter nodules were detected in the lungs and were followed with CT scans.