Timing of cytoreductive nephrectomy impacts survival in mRCC
medwireNews: Patients with metastatic renal cell carcinoma (mRCC) who respond to tyrosine kinase inhibitor (TKI) therapy may have better outcomes if they are treated with this targeted therapy before rather than after cytoreductive nephrectomy (CRN), study findings show.
"Primary TKI therapy may act to limit the progression of metastatic disease by delivering early systemic treatment to eliminate micrometastatic disease and may identify nonresponders who are unlikely to benefit from CRN," suggest Ithaar Derweesh (Moores UCSD Cancer Center, La Jolla, California, USA) and colleagues. "Emerging reports have provided encouraging results with this strategy."
The researchers found that among patients who responded to the TKI sunitinib, those who received the therapy before CRN had a significantly lower risk for death from mRCC than those who received primary CRN followed by adjuvant sunitinib, at 9.1% versus 58.8%. The findings were similar for overall death, at 9.1% versus 64.7%.
Patients who did not respond to primary sunitinib therapy and did not undergo CRN had disease-specific and overall death rates of 85.7% each.
In all, 17 patients with mRCC underwent primary CRN followed by adjuvant sunitinib (group 1), while 18 underwent primary sunitinib therapy followed by planned CRN (group 2).
Tumor characteristics were similar between the two groups, with an average tumor size of 9.2 cm in group 1 and 10.4 cm in group 2. Sunitinib treatment in patients in group 1 was started a median 1.4 months postoperatively and patients received a median of 6 cycles.
The patients in group 2 received a median of 3 cycles of sunitinib therapy and 11 (61%) achieved at least a partial response, with a median 24% reduction in primary tumor diameter. These patients went on to receive CRN a median 6 months after diagnosis. Disease progressed in the remaining seven (39%) patients, and they received salvage systemic therapy rather than undergoing surgery (group 2 no-CRN).
Multivariate analysis, including variables such as age, race, body mass index, disease severity, and tumor size and grade, showed that treatment type was the only significant predictor for disease-specific and overall death.
The hazard ratios for disease-specific death, for example, were 10.17 for group 2 no-CRN versus group 1 patients; 7.24 for patients in group 1 versus patients in group 2 +CRN; and 73.65 for group 2 no-CRN patients versus those who received CRN.
The researchers note in Urology that primary TKI did not complicate CRN. Surgical complications occurred in 35.7% of patients, but there was no significant difference in overall complication rate between the primary TKI and CRN groups.
They conclude: "Preoperative TKI therapy before CRN may allow more selective application of surgery.
"Further investigation is required to assess the role, timing, and sequencing of targeted therapy and CRN in the treatment of mRCC."
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Lucy Piper, Senior medwireNews Reporter