In Malaysia, renal cell cancer or kidney cancer present at stage 4 in 50% of cases.
Cases are detected incidentally during imaging (USG, CT scans), more than those who present with the classical triad of flank pain, gross hematuria and palpable abdominal mass.
Histologically, 80% are of clear cell type and if one is to get renal cell cancer, this is the histology you want because almost all studies and medications for RCC are indicated for clear cell type.
For stage 1, 2 and 3 renal cell cancer, there treatment is just radical nephrectomy and nothing more besides close surveillance. There is no proven treatment that had shown benefits in adjuvant setting.
For stage 4 or MRCC, the treatment are mainly targeting at VEGF pathway. Chemotherapy plays no role whatsoever in treatment of MRCC.
VEGF is a regulator of tumor angiogenesis. VEGF stands for ‘vascular endothelial growth factor’. VEGF stimulates vascular endothelial cell growth, survival, and proliferation.
Once patient is diagnosed as advanced/ stage 4 renal cell cancer, what is the next step?
The first step is to determine the patient’s IMDC risk groupings, which will become more important soon to decide on best treatment.
Currently, the common practice is to start patients on either pazopanib or sunitinib no matter which risk group the patient belongs to, even in poor risk group.
Patient will be asked some questions in history taking to determine patient performance status (is there restriction in any physical strenuous activity?).
Also, time from initial diagnosis (including original localized disease) to treatment for advanced renal cell cancer is determined to see if it’s more or less than 1 year. (Poorer prognosis and more aggressive cancer if it’s less than 1 year)
Finally, four laboratory investigations; haemoglobin, platelet, neutrophil and calcium levels are needed. (Prepare your full blood count (FBC) and calcium/ albumin investigation report).
International Metastatic RCC Database Consortium (IMDC) score, consists of 6 risk factors and each carry 1 point:
- Karnofsky performance status (PS) <80%
- Haemoglobin <lower limit of normal
- Time from diagnosis to treatment of < 1 year
- Corrected calcium > upper limit of normal
- Platelets > upper limit of normal
- Neutrophils > upper limit of normal
Different IMDC risk groups will results in different median overall survival and also different suitable treatments.
Still, if one presented with stage 4 renal cell cancer but the metastatic foci is limited and BOTH the primary and metastatic foci can be resected, cure is still possible by surgical resection and no further treatment is needed after that.
The main treatment for advanced/ stage 4 renal cell cancer are VEGF inhibitors; pazopanib and sunitinib.
In the past when there are not much difference in progression free survival (PFS) or median overall survival (OS) for VEGF inhibitors, much attention was given over which VEGF inhibitors (monotherapy) had the lowest side effects profile.
However, with the plethora of positive results reported this year using immunotherapy in advanced renal cell cancer, some international guidelines had already updated their first line treatment for advanced/ stage 4 renal cell cancer to include immunotherapy as not only first line but also first option; as in the case of nivolumab + ipilimumab for intermediate and poor-risk group patients.
It’s definitely going to be more exciting in coming years as we’d just seen in early phase 2 trial (pembrolizumab + axitinib), which reported doubling of PFS, high overall response rate (73%) and rarely seen 7.7% of patients achieving complete response!
Phase 3 KEYNOTE-426 trial is in progress to confirm the results but, I doubt anyone who can afford this treatment will want to wait or can wait for so long.