palliative radical nephrectomy:Metastatic Renal cell Carcinoma

A 75-year-old gentleman came to us after he was diagnosed to be having left renal mass.He initially had back pain for which he consulted spine surgeon.After initial conservative therapy failed;he was subjected to MRI spine.MRI revealed metastatic foci in dorsolumbar vertebrae.

His staging work up revealed enhancing midpolar mass in left kidney.The mass appeared to be confined to the kidney only although there was ipsilateral psoas thickening.It also revealed basal metastatic lung lesions.We came to conclusion of metastatic renal cell carcinoma.

As the patient had a good performance index and preserved biochemical and hematological parameters he was advised palliative nephrectomy.

The open radical nephrectomy was performed ; the post-operative course was uneventful.The final Histopathology read as Renal cell Carcinoma -Furhmann Grade 3 with T3 stage.

He is planned for Sunitinib therapy.(Sutent 50 mg cap/day ) along with possible radiation to the spine if needed.

REVIEW OF LITERATURE:

Renal cell carcimoma (RCC) is the third most common genitourinary cancer after prostate and bladder. Majority (80% to 85%) of kidney tumors are malignant. It is the most lethal malignancy of all urological cancers.Unique characteristics of RCC lack of early warning signs,§ diverse clinical§ manifestations, resistance to radiation and chemotherapy, and immunogenic nature and spontaneous regressions.

Pretreatment features associated with shorter survival

There are various studies identifying the pretreatment factors associated with poor survival. These are – Low Karnofsky performance status (< 80%)– High lactate dehydrogenase level (> 1.5 x normal)– Low hemoglobin level– High serum calcium– Absence of nephrectomy• Nephrectomy and resection of metastases has been reported to prolong the survival. Effect is enhanced with long disease-free interval between initial nephrectomy and development of metastases.

Survival also depends on the site of metastasis. Patients with lung metastasis only have better survival than those with other site metastasis. (Flanigan RC, et al. N Engl J Med. 2001; 345: 1655-1659.)

Available treatment modalitiesOptions for chemotherapy and endocrine-based approaches are limited, and no hormonal or chemotherapeutic regimen is accepted as a standard of care. Therefore, various biologic therapies have been evaluated. New agents, such as sorafenib and sunitinib, having anti-angiogenic effects through targeting multiple receptor kinases, and have been investigated in patients failing immunotherapy.

Role of Surgery Palliative nephrectomy should be considered in patients with metastatic disease for alleviation of symptoms such as pain, hemorrhage, malaise. Several randomized studies are now showing improved overall survival in patients presenting with metastatic kidney cancer who have nephrectomy followed by either interferon or IL-2. If the patient has good physiological status, then nephrectomy should be performed prior to immunotherapy. There are anecdotal reports documenting regression of metastatic renal cell carcinoma after removal of the primary tumor but adjuvant nephrectomy is not recommended for inducing spontaneous regression; rather, it is performed to decrease symptoms or to decrease tumor burden for subsequent therapy in carefully controlled environments. About 25-30% of patients have metastatic disease at diagnosis, and fewer than 5% have solitary metastasis. Surgical resection is recommended in selected patients with metastatic renal carcinoma. This procedure may not be curative in all patients but may produce some long-term survivors. The possibility of disease-free survival increases after resection of primary tumor and isolated metastasis excision.

RADIATION THERAPY:Radiation therapy may be considered as the primary therapy for palliation in patients whose clinical condition precludes surgery, either because of extensive disease or poor overall condition. A dose of 4500 centigray (cGy) is delivered, with consideration of a boost up to 5500 cGy. Preoperative radiation therapy has not been found to yield any survival advantage. Controversies exist concerning postoperative radiation therapy, but it may be considered in patients with peri-nephric fat extension, adrenal invasion, or involved margins. A dose of 4500 cGy is delivered, with consideration of a boost. Palliative radiation therapy often is used for local or symptomatic metastatic disease, such as painful osseous lesions or brain metastasis, to halt potential neurological progression. Surgery also should be considered for solitary brain or spine lesions, followed by postoperative radiotherapy. Stereotactic radiosurgery is more effective than surgical extirpation for local control and can be performed on multiple lesions.

Multi-kinase inhibitors:

Sunitinib (Sutent) Sunitinib is another multi-kinase inhibitor approved by the FDA in January 2006 for the treatment of metastatic kidney cancer that has progressed after a trial of immunotherapy. The approval was based on the high response rate (40% partial responses) and a median time to progression of 8.7 months and an overall survival of 16.4 months. The receptor .b and atyrosine kinases inhibited by sunitinib include VEGFR 1-3 and PDGFR Major toxicities (grade II or higher) include fatigue (38%), diarrhea (24%), nausea (19%), dyspepsia (16%), stomatitis (19%), and decline in cardiac ejection fraction (11%). Dermatitis occurred in 8%, and hypertension occurred in 5% of patients. A recent phase 3 study evaluating sunitinib in the first-line setting, , in patients with metastatic RCC demonstrated significantacompared against IFN- improvement in PFS and response rates compared against the control arm. These results are considered to be preliminary, and longer-term follow-up is necessary for conclusive results.Other multi-kinase inhibitors undergoing investigation for RCC Lapatinib is an EGFR and ErbB-2 dual tyrosine kinase inhibitor, which appears to have efficacy in the treatment of tumors, including RCC, which overexpress EGFR. This was recently reported in a phase 3 study in advanced RCC evaluating lapatinib against hormonal therapy in patients who had failed prior therapy.RAD001 (Everolimus) is a serine-threonine kinase inhibitor of mTOR, an important regulatory protein in cell signaling. A recent phase 2 trial in patients with metastatic RCC demonstrated promising preliminary clinical results