title: Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  The preliminary experience with neoadjuvant therapy for the surgical management of RCC was reviewed at two large referral centres. Several unique patients were identified who had a novel response to systemic therapy that altered the surgical strategy.
  
  
  RESULTS
  Four 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.
  
  
  CONCLUSIONS
  The 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 immunotherapeutic-based 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.
authors.affiliation: Department of Urology, David Geffen School of Medicine, University of California-Los Angeles, CA 90095, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Shuch
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Riggs
authors.forename: Jeff C
authors.initials: JC
authors.lastname: LaRochelle
authors.forename: Fairooz F
authors.initials: FF
authors.lastname: Kabbinavar
authors.forename: Raffi
authors.initials: R
authors.lastname: Avakian
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Patard
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009392:Nephrectomy / Q000379:methods*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib