The patient was healthy until a few months ago when he complained of right flank discomfort. An abdominal ultrasound had revealed a left renal lesion. Subsequent abdominal CT demonstrated a solid lesion with necrotic content at a size of 9X6.5cm. There were no other pathological findings on the scan and the patient had an abdominal radical nephrectomy.
Surgery took place on June 2005; radical nephrectomy with ipsilateral para-aortic lymph node dissection was performed. Tissue was sent for routine histopathology as well as immediate freezing of some tumor tissue for future investigation, if needed. Pathology diagnosis was a 9 cm clear cell renal carcinoma, nuclear grade Fuhrman 3, with the tumor infiltrating renal capsule and focally penetrating the perinephric fatty tissue (pT3a). Adrenal gland and lymph nodes were free of tumor. Recovery was uneventful. Postoperative creatinine levels stabilized at 1.6mg/dl with normal LFT and CBC.
Making use of recently published data regarding tumor free survival of patients with clear cell type renal carcinoma (Sorbellini et al, J Urol 173; 48-51, Jan 05) The patient has a chance of about 80% recurrence free survival at 5 years. A close routine follow up should be done. This will comprise of history & physical examination, blood tests & chest X-ray every 6 months for the first three years of follow up and yearly thereafter. Abdominal CT should be done in a year time and every 2 years thereafter. Such a follow up performed on a timely fashion will enable early diagnosis of disease and prompt treatment.
Another aspect that should be addressed is the genetic aspect. It is well known that 8% of newly diagnosed sporadic cases of patients with clear cell renal carcinoma carry a VHL gene mutation. The patient has negative family history for cancer cases and has no clinical signs & symptoms or radiological findings of any other abdominal tumor. In the absence of neurological symptoms I do not recommend head CT to rule out CNS lesions. Seventy percent of VHL affected patients develop retinal angiomas. They may be asymptomatic and are easily detected on routine opthalmoscopy, which I recommend in the near future. If such lesions are found genetic counseling is warranted.
The case was sent to online second opinion through Medical Opinion ( ). the prior oncologic history included keft radical nephrectomy with ipsilateral para-aortic lymph node dissection, 9 cm conventional renal cell carcinoma, nuclear grade Fubnnan 3, with tumor infiltrating renal capsule and focally penetrating perinephric fat tissue (pT3aNOMO).
The patient has apparently recovered without any incidence since his surgery but it is pursuing a second opinion with regard to the benefit of any additional therapy and with questions as to how he should be followed.
There is no information provided as to how the patient is doing since the completion of his nephrectomy and I will assume that he is in good physical condition. Therefore, one could include as part of his staging, the UCLA Integrated Staging System, which was developed from a retrospective analysis of 661 patients undergoing nephrectomy. According to this staging classification, which is based on stage Fuhrman grade, because performance status and additional prognostic factors, the patient has a UISS Stage of 2. This is assuming that he has Stage III disease with high-grade Fuhrman 3, and an ECOG performance status of 0. Based on this data, his two year percentage of survival would be 89%, however if he had any debilitation or pain and his ECOG performance status was 1 or more, he would have only a 66% two-year survival. A five-year survival rate for UISS survival stage is 64%. He, therefore, is at some risk for recurrence from his renal cell carcinoma; however there is no evidence that adjuvant therapy is helpful in this setting at the present time. Three Phase III trials have been conducted using either adjuvant interferon or inerleukin-2 versus observation in patients with resected locally advanced renal cell carcinoma. None of these studies demonstrated a survival benefit and toxicities expected with these agents were seen in patients assigned to the treatment arms. Adjuvant vaccine trials are currently an ongoing area of investigation. There is a Phase II study of vaccine comprising HLA*A2 and HLA-A3 binding peptides from FOP factor 5 in patients with Stage III or IV renal cell carcinoma that is currently being offered at the National Cancer Institute by Dr. James Yang. Additionally, there is a study of monoclonal antibody therapy, CG250 versus placebo antibody for patients with clear cell cancer after nephrectomy sponsored by Wilex Pharmaceuticals that is also accruing patients in the United States for which the lead investigator is in California; but additional sites throughout the United States are open.
My understanding is that there was some exploratory vaccine therapy being done directed against the VHL protein, however I do not see that on our current clinical trials database. My recommendation, therefore, is that the patient considers either standard of care which would be close observation every four months for two years and then every six months for three years, and then annually, which would include a history and physical, chest x-ray, comprehensive metabolic panel, and an abdominal CT scan. Alternatively, patient could consider participating in an adjuvant vaccine trial or monoclonal antibody therapy trial such as the ones I mentioned above.
