RCC in Adolescents and Young Adults (AYAs): Diagnosis and Management Nicholas G. Cost, M.D. Assistant Professor, Department of Surgery, Division of Urology University of Colorado Cancer Center Fifteenth International Kidney Cancer Symposium November 4-5, 2016 Marriott Miami Biscayne Bay, Miami, Florida, USA www.kidneycancersymposium.com
Disclosure I have no relevant financial relationship with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity. I do not intend to discuss an unapproved or investigative use of a commercial product/device in my presentation. I serve as a Children s Oncology Group (COG) Renal Tumor Committee Member, but I am not speaking of their behalf and all opinions expressed today are my own and do not represent that of COG.
Goals 1. Review epidemiology of RCC in Adolescents and Young Adults (AYAs) 2. Describe histology of AYA RCC 3. Discuss management of AYA RCC 4. Review available oncologic outcome data on AYA RCC 5. Present new clinical trial aimed at AYAs with TFE+ RCC
Scope of the Problem Renal Cell Carcinoma is rare in Adolescents and Young Adults (AYAs) Overall incidence of 0.01 per 100,000 population Prospective Registry Data from the Children s Oncology Group (COG) study AREN 03B2 indicate: RCC is the 2 nd most common etiology of Renal Malignancy in those up to 30 years old RCC passes Wilms Tumor around age 11-12 years old RCC comprises 3.7% of all primary Renal Malignancies in children and AYAs Akhavan et al. J Urol. 2015. Geller et al. Cancer 2015.
Increasing Incidence Bleyer et al : Cancer Epidemiology in AYAs 15-29 Years of Age, Including SEER Incidence and Survival: 1975-2000.
RCC Histology in AYAs Older data failed to recognize Translocation (TFE+) type RCC Advantage of AREN 03B2 Data - included central pathology review 1. 46.7% TFE+ (Translocation) RCC 2. 20.8% RCC NOS (likely unidentified genetic driver) 3. 16.7% Papillary RCC 4. 10.8% Renal Medullary Carcinoma 5. 3.3% Chromophobe RCC 6. 0.8% Clear Cell RCC Geller et al. Cancer 2015
Geller et al. Cancer 2015
Lymph Node Involvement Lymph node (LN) involvement (N+) was found in 35 of 73 cases (47.9%) for which LNs were sampled Including 19 of 40 (47.5%) with T1 (<7 cm) primary tumors Using a size cutoff of 1 cm, for imaging definition of + LN: Sensitivity of 57.1% (20 of 35; 95% CI, 39.4%-73.7%) Specificity of 94.6% (35 of 37; 95% CI, 81.8%-99.3%) A total of 49 patients (40.8%) failed to have LNs sampled Geller et al. Cancer 2015
Metastatic Disease Distant metastases (M+) were present in 22 cases (18.3%) Lung in 15 patients (12.5%) Liver in 7 patients (5.8%) Bone in 3 patients (2.5%) Overall 48 patients (40%) presented with either lymphatic or hematogenous spread of RCC Geller et al. Cancer 2015
Geller et al. Cancer 2015
Geller et al. Cancer 2015
Geller et al. Cancer 2015
Conclusions from AREN 03B2 TFE+ RCC is the most common histology in AYA RCC LN involvement is common and observed even among patients with small primary tumors Failure to sample LNs results in incomplete staging and potentially inadequate disease control for these patients
Oncologic Outcomes in AYA RCC Based on single institution and administrative data COG data from AREN 0321 not yet published
Rialon et al. J Peds Surg 2015.
Rialon et al. J Peds Surg 2015.
Akhavan et al. J Urol. 2015.
Surgical Management Radical Nephrectomy Predominate approach, especially in younger patients and larger tumors Nephron Sparing Surgery (Approximately 15-20% of cases) Most used with smaller tumors (pt1) appears reasonable in pt1 Poor rates of LN sampling with NSS Reports of robotic approaches to NSS (can still get adequate LNs)
Role of LN Dissection Reports of improved survival in those who had LN+ disease who had an extended LND (Indolfi et al.)
Rialon et al. J Peds Surg 2015.
Role of LN Dissection Similar data exist in adult RCC with a survival advantage with RPLND in those with N+ disease Thomas et al - approximately 40% 10 yr CSS after RPLND in those with isolated retroperitoneal recurrence Thus, appears rational to do LND if RCC suspected Also, if +LNs found, reasonable to do RPLND even as a 2 nd procedure
Role of Metastectomy In general, only long term survivors with metastatic disease are those made NED by surgical resection No known curative medical therapy Stage IV Rialon et al. J Peds Surg 2015.
Role of Medical Therapy HD IL-2 Not reported to be beneficial in this age group Likely due to low incidence of true ccrcc Targeted Agents Reports of clinical response to Sunitinib and other TKIs Also, some mechanistic rationale for mtor inhibition Cytotoxic Chemotherapy Reports of limited response to Gem/Dox or Gem/Ox regimens analogous to those used in Sarcomatoid RCC no reported long term responders
Future Study COG Study AREN 1621 Randomized Phase 2 Trial of Axitinib/Pembrolizumab combination therapy vs. single agent Axitinib or Pembrolizumab for the treatment of TFE/Translocation Renal Cell Carcinoma across all age groups: Arm A: Axitinib + Pembrolizumab Arm B: Axitinib Arm C: Pembrolizumab Stratified by age and prior systemic therapy Will be available to adult institutions via NCTN National Clinical Trials Network of the NCI
COG AREN 1621 Inclusion Criteria: Age 1 year old Histologically confirmed translocation morphology RCC Unresectable or Metastatic and Measurable disease as defined by RECIST Inability to undergo complete resection of the disease by surgery
COG AREN 1621 Exclusion Criteria: Prior PD-1 and PD-L1 directed therapy Prior anti-vegf therapy Chemotherapy, Targeted Therapy or XRT within 2 weeks
COG AREN 1621 Schema: Absent disease progression or intolerable toxicity, patients may continue on study drug for up to 2 years duration Tumor disease status imaging will be assessed after cycles 2, 4, 6 and then every 3 months thereafter, or at any time clinical progression is suspected
COG AREN 1621 Primary Endpoint: Progression-Free Survival (PFS) The primary comparisons are between Axitinib and concurrent Axitinib + pembrolizumab and between pembrolizumab and concurrent Axitinib + pembrolizumab. The study is powered to detect a difference in median PFS time of 6 months
Conclusions AYA RCC is rare overall, but incidence is increasing AYA differs from typical adult RCC TFE+ RCC is most common type of AYA RCC Increased incidence of advanced disease Possible benefits for aggressive surgical resection Lymph Node Dissection New clinical trial on the horizon!
Conclusions Thank you! Questions or Comments? Please feel free to contact me anytime for questions nicholas.cost@ucdenver.edu Fifteenth International Kidney Cancer Symposium November 4-5, 2016 Marriott Miami Biscayne Bay, Miami, Florida, USA www.kidneycancersymposium.com