Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm

Abstract

Several unique patients were identified who had a novel response to systemic therapy that altered the surgical strategy. RESULTSFour patients who had targeted therapy before surgery are described and in whom there were effects on tumour biology not seen previously with chemotherapy and cytokine therapy. The selected patients who had neoadjuvant targeted therapy had shrinkage of a tumour thrombus in the inferior vena cava, nodal involvement, renal fossa recurrence and tumour within a solitary kidney. CONCLUSIONSThe introduction of new molecular agents has revolutionized the treatment of patients with metastatic RCC. Responses to targeted therapy within the primary tumour, tumour thrombus, renal fossa recurrence, and lymph node metastases are novel findings not seen during treatment with immunotherapeuticbased strategies. This might be a signal for urological surgeons to re-evaluate the paradigm for the surgical management of advanced RCC. Potential applications are presented to encourage further investigations with targeted therapy in the neoadjuvant setting. OBJECTIVETo evaluate our early experience with neoadjuvant therapy (sunitinib or sorafenib) in advanced renal cell carcinoma (RCC), to explore the effect on both tumour biology and potential for downstaging advanced tumours, as systemic therapy for RCC has historically resulted in little if any primary tumour response, but recent experience with targeted therapy suggests otherwise. PATIENTS AND METHODSThe preliminary experience with neoadjuvant therapy for the surgical management of RCC was reviewed at two large referral centres.

Tratamiento de los tumores renales localmente avanzados

“…El tratamiento neoadyuvante con inhibidores de la angiogénesis, que han demostrado su eficacia en tumores metastási-cos, puede disminuir la masa tumoral facilitando así su resecabilidad quirúrgica, y con ello su supervivencia. No existe ningún estudio aleatorizado que aporte un grado de evidencia suficiente para recomendar el tratamiento neoadyuvante en estos pacientes, pero sí existen pequeñas series en las que se observa una disminución del tamaño tumoral, del estadio tumoral e incluso del tamaño del trombo vascular [35][36][37][38] . En la mayor parte de los casos se utilizan sorafenib o sunitinib con asociación de bevacizumab o incluso INF-a en algún paciente.…”

Successful Treatment of T4 Renal Cell Carcinoma After a Neoadjuvant Targeted Therapy Using Sunitinib: Report of a Case

“…Some recent publications have suggested promising results with neoadjuvant therapy, including partial remission of the primary tumor, vena cava thrombus, and lymph node metastases [2][3][4][5][6][7]. We present the case of a patient who underwent successful resection of T4 RCC after a neoadjuvant targeted therapy using sunitinib, and review the pertinent literature.…”

Adjuvant and Neoadjuvant Therapy in Renal Cell Carcinoma

“…A slight decrease of this magnitude in the size of the primary tumor is unlikely to be of clinical relevance. In addition, the role of neoadjuvant treatment in simplifying the surgical resection and making the tumor amenable to an elective nephron-sparing surgery is also questionable [83]. However, patients who have involvement of the IVC (T3b or T3c) will probably benefit more from targeted therapies as the decrease in the tumor volume facilitates the surgical procedure [84].…”