Is There a Role for Neoadjuvant Targeted Therapy to Downsize Primary Tumors for Organ Sparing Strategies in Renal Cell Carcinoma?

Abstract

With an increasing number of small renal masses being diagnosed organ-preserving treatment strategies such as nephron-sparing surgery (NSS) or radiofrequency and cryoablation are gaining importance. There is evidence that preserving renal function reduces the risk of death of any cause, cardiovascular events, and hospitalization. Some patients have unfavourable tumor locations or large tumors unsuitable for NSS or ablation which is a clinical problem especially in those with imperative indications to preserve renal function. These patients may benefit from downsizing primary tumors by targeted therapy. This paper provides an overview of the current evidence, safety, controversies, and ongoing trials.

Sunitinib Stimulates Expression of VEGFC by Tumor Cells and Promotes Lymphangiogenesis in Clear Cell Renal Cell Carcinomas

“…40). However, the benefits of neoadjuvant antiangiogenic treatments have yet to be validated clinically (40), thus examination of patient materials is rarely performed. However, we obtained 13 patient samples (from a total of 3,000) that were treated with antiangiogenic therapy in a neoadjuvant setting in different French hospitals ( Supplementary Table S1A).…”

Presurgical neoadjuvant targeted molecular therapy for kidney cancer with concomitant vena cava tumor embolus: A clinical study

“…This effect was observed in the present study, during which, the level of the tumor thrombus was decreased following sunitinib treatment, including two cases that were downgraded from tumor thrombus level IV to II, one case from level IV to III and two cases from level III to II. The majority of previous studies have demonstrated that targeted therapy is able to downsize RCC tumors in order to allow organ-sparing surgeries to be performed (11,17), including a partial nephrectomy for patients with localized and advanced RCC (18). Downstaging may also decrease the risk of recurrence (10).…”

“…The ESMO guidelines recommend a period of early observation following diagnosis (21). Bex et al (17) reported that the indications for neoadjuvant targeted molecular therapy include RCC with vena cava tumor embolus level III/IV and RCC at the tumor-node-metastasis system stage T1b or T2 as suitable for partial nephrectomy (bilateral RCC or solitary kidney) or as tentative therapy for advanced RCC prior to cytoreductive surgery (18,19). For patients with tumor embolus level III or lower, presurgical neoadjuvant targeted molecular therapy may be considered to reduce tumor size if the imaging examinations suggest that resection is impossible due to the tumor embolus being adhered to the vena cava wall (12).…”

The role of transesophageal echocardiography in the management of renal cell carcinoma with venous tumor thrombus

“…Currently, no available systemic therapies have achieved a significant clinical response, and none are curative when used alone. While multiple studies have investigated the use of neoadjuvant systemic therapy to decrease tumor thrombus burden, this has demonstrated mixed results and could potentially cause a harmful delay in surgical resection which may result in tumor progression . Interestingly, operative mortality increases from 2% to as much as 9.3% when IVC extension is present .…”

“…While multiple studies have investigated the use of neoadjuvant systemic therapy to decrease tumor thrombus burden, this has demonstrated mixed results and could potentially cause a harmful delay in surgical resection which may result in tumor progression. 9,10 Interestingly, operative mortality increases from 2% to as much as 9.3% when IVC extension is present. 11 However, more modern series have shown less discrepant rates in mortality, likely owing to improved surgical and imaging techniques.…”