NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
`
`Kidney Cancer
`
`Version 1.2017 — September 26, 2016
`
`NCCN.org
`
`NCCN Guidelines for Patients® available at www.nccn.org/patients
`
`Continue
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0001
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`*
`
`*
`
`NCCN Guidelines Version 1.2017 Panel Members
`Kidney Cancer
`John L. Gore, MD, MS ω
`Robert J. Motzer, MD/Chair † Þ
`Memorial Sloan Kettering Cancer Center
`Fred Hutchinson Cancer Research Center/
`Seattle Cancer Care Alliance
`Eric Jonasch, MD/Vice-chair †
`The University of Texas
`MD Anderson Cancer Center
`Neeraj Agarwal, MD ‡ †
`Huntsman Cancer Institute
`at the University of Utah
`
`NCCN Guidelines Index
`Kidney Cancer TOC
`Discussion
`
`Phillip M. Pierorazio, MD ω
`The Sidney Kimmel Comprehensive
`Cancer Center at Johns Hopkins
`
`Elizabeth R. Plimack, MD, MS †
`Fox Chase Cancer Center
`Bruce G. Redman, DO †
`University of Michigan
`Comprehensive Cancer Center
`
`Steven L. Hancock, MD § Þ
`Stanford Cancer Institute
`
`Michael R. Harrison, MD †
`Duke Cancer Institute
`
`Sam Bhayani, MD ω
`Siteman Cancer Center at Barnes-
`Jewish Hospital and Washington
`University School of Medicine
`
`William P. Bro ¥
`Kidney Cancer Association
`
`Sam S. Chang, MD ω
`Vanderbilt-Ingram Cancer Center
`
`Toni K. Choueiri, MD † Þ
`Dana-Farber/Brigham and Women’s
`Cancer Center
`Brian A. Costello, MD, MS †
`Mayo Clinic Cancer Center
`Ithaar H. Derweesh, MD ω
`UC San Diego Moores Cancer Center
`
`Mayer Fishman, MD, PhD † Þ ‡
`Moffitt Cancer Center
`
`Thomas H. Gallagher, MD Þ
`Fred Hutchinson Cancer Research Center/
`Seattle Cancer Care Alliance
`
`Won Kim, MD †
`UCSF Helen Diller Family
`Comprehensive Cancer Center
`
`Christos Kyriakopoulos, MD ‡
`University of Wisconsin
`Carbone Cancer Center
`
`Chad LaGrange, MD ω
`Fred & Pamela Buffett Cancer Center
`Elaine T. Lam, MD †
`University of Colorado Cancer Center
`
`Clayton Lau, MD ω
`City of Hope Comprehensive Cancer Center
`M. Dror Michaelson, MD, PhD †
`Massachusetts General Hospital
`Cancer Center
`Thomas Olencki, DO †
`The Ohio State University Comprehensive
`Cancer Center - James Cancer Hospital
`and Solove Research Institute
`
`Brian Shuch, MD ω
`Yale Cancer Center/Smilow Cancer Hospital
`Brad Somer, MD †
`St. Jude Children’s Research Hospital/
`University of Tennessee Cancer Institute
`Guru Sonpavde, MD †
`University of Alabama at Birmingham
`Comprehensive Cancer Center
`
`Jeffrey Sosman, MD ‡
`Robert H. Lurie Comprehensive Cancer
`Center of Northwestern University
`
`NCCN
`Mary Dwyer, MS
`Rashmi Kumar, PhD
`
`† Medical oncology
`‡ Hematology/hematology oncology
`§ Radiotherapy/Radiation oncology
`Þ Internal medicine
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`NCCN Guidelines Panel Disclosures
`
`ω Urology
`≠ Pathology
`¥ Patient advocacy
`*Discussion writing
`committee member
`
`Continue
`
`Ex. 1091-0002
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`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Version 1.2017 Table of Contents
`Kidney Cancer
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`NCCN Kidney Cancer Panel Members
`Summary of the Guidelines Updates
`
`Initial Workup (KID-1)
`Primary Treatment and Follow-Up for Stage I-III (KID-1)
`Primary Treatment for Stage IV (KID-2)
`
`Relapse and Stage IV Surgically Unresectable Disease
`First-Line Therapy and Subsequent Therapy for Predominant Clear Cell Histology
`(KID-3)
`Systemic Therapy for Non-Clear Cell Histology (KID-4)
`
`Principles of Surgery (KID-A)
`Follow-up (KID-B)
`Predictors of Short Survival Used to Select Patients for Temsirolimus (KID-C)
`
`Staging (ST-1)
`
`Clinical Trials: NCCN believes that
`the best management for any patient
`with cancer is in a clinical trial.
`Participation in clinical trials is
`especially encouraged.
`To find clinical trials online at NCCN
`Member Institutions, click here:
`nccn.org/clinical_trials/physician.html.
`NCCN Categories of Evidence and
`Consensus: All recommendations
`are category 2A unless otherwise
`specified.
`See NCCN Categories of Evidence
`and Consensus.
`
`The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.
`Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical
`circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or
`warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
`Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may
`not be reproduced in any form without the express written permission of NCCN. ©2016.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0003
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Version 1.2017 Updates
`Kidney Cancer
`Updates in Version 1.2017 of the NCCN Guidelines for Kidney Cancer from Version 3.2016 include:
`KID-1
`KID-3 (continued)
`• Initial workup
`Subsequent Therapy
`4th bullet was revised by adding " ±" to "Abdominal ± pelvic CT"
` ◊ The category designation for the following options were revised:
`5th bullet, chest imaging was clarified as "chest x-ray" and "Chest CT" was
` – Lenvatinib + everolimus was changed from a category 2A to
`added to the "If clinically indicated" bullet.
`category 1 designation.
`Footnote "a" was added, "Imaging with contrast when clinically indicated."
` – Everolimus was category 1 after antiangiogenic therapy and after
`Also added to all KID-B pages.
`cytokine therapy and is now a category 2A.
`• Primary treatment
` – Pazopanib was category 2A after antiangiogenic therapy and a
`For Stage I (pT1a), the option for ablative techniques was revised: "Ablative
`category 1 after cytokine therapy and is now a category 2A.
`techniques in selected patients for non-surgical candidates"
` – Sorafenib was category 2A after antiangiogenic therapy and a
`For Stage II, III, "Partial nephrectomy, if clinically indicated" was added.
`category 1 after cytokine therapy and is now a category 2A.
` – Sunitinib was category 2A after antiangiogenic therapy and a
`category 1 after cytokine therapy and is now a category 2A.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`KID-2
`• Stage IV
`Primary treatment for potentially surgically resectable primary with multiple
`metastatic sites was revised: "Cytoreductive nephrectomy in select patients
`prior to systemic therapy."
`For surgically unresectable, "tissue sampling" was added before first-line
`therapy.
`
`KID-3
`• Predominant clear cell histology
`First-line therapy
` ◊ The first-line therapy options were reorganized and "alphabetical by
`category and preference" was added to the heading.
` ◊ "Preferred" was added to both sunitinib and pazopanib.
`Subsequent therapy
` ◊ The subsequent therapy options were reorganized by removing the "After
`antiangiogenic therapy" and "after cytokine therapy" categories and
`adding "Alphabetical by category and preference" to the heading.
` ◊ "Preferred" was added to cabozantinib (category 1) and nivolumab
`(category 1)
`
`The following footnotes were removed from this page:
` ◊ "Category 1 recommendations are listed in order of FDA approval."
` ◊ "Currently available tyrosine kinase inhibitors used in first-line
`therapy include: axitinib, pazopanib, sorafenib, or sunitinib."
`
`KID-4
`• Non-clear cell histology
` ◊ The systemic therapy options were reorganized and "alphabetical by
`category and preference" was added to the heading.
` ◊ "Preferred" was added to sunitinib
` ◊ Cabozantinib was added with a category 2A designation.
` ◊ Lenvatinib + everolimus was added with a category 2A designation.
` ◊ Nivolumab was added with a category 2A designation.
`KID-A
`• Principles of surgery
`1st bullet, 1st sub-bullet was revised from "Small unilateral tumors
`(Patients with T1a and selected T1b and T2a tumors)" to "Unilateral
`Stage I-III tumors where technically feasible."
`6th bullet, 1st sub-bullet was revised, "Can be considered for
`selected patients with clinical stage T1 renal lesions who are not
`surgical candidates."
`
`KID-B 1 of 4
`• Follow-up
`Bullet regarding pelvic imaging was revised, "Pelvic imaging CT or
`MRI, as clinically indicated"
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`UPDATES
`
`Ex. 1091-0004
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`INITIAL WORKUP
`
`STAGE
`
`PRIMARY TREATMENTc
`
`FOLLOW-UPd
`(category 2B)
`
`Suspicious
`mass
`
`• H&P
`• CBC, comprehensive
`metabolic panel
`• Urinalysis
`• Abdominal ± pelvic CTa
`or abdominal MRIa
`• Chest x-ray
`• If clinically indicated
`Bone scan,
`Brain MRIa
`Chest CTa
`Consider needle
`biopsyb
`• If urothelial carcinoma
`suspected (eg, central
`mass)
`Consider urine
`cytology, ureteroscopy
`
`Partial nephrectomy
`(preferred)
`or
`Radical nephrectomy
`(if partial not feasible
`or central location)
`or
`Active surveillance in
`selected patients
`or
`Ablative techniques
`in selected patients
`
`Partial nephrectomy
`or
`Radical nephrectomy
`
`Radical nephrectomy
`or
`Partial nephrectomy,
`if clinically indicated
`
`See KID-2
`
`Stage I
`(pT1a)
`
`Stage I
`(pT1b)
`
`Stage
`II, III
`
`Stage
`IV
`
`Follow-up
`(See KID-B)
`
`Relapse
`See First-Line
`Therapy (KID-3)
`
`aImaging with contrast when clinically indicated.
`bBiopsy of small lesions may be considered to obtain or confirm a diagnosis of malignancy and guide surveillance, cryosurgery, and radiofrequency ablation strategies.
`cSee Principles of Surgery (KID-A).
`dNo single follow-up plan is appropriate for all patients. Follow-up should be individualized based on patient requirements.
`
`KID-1
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0005
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`STAGE
`
`PRIMARY TREATMENTc
`
`Potentially surgically
`resectable primary with
`solitary metastatic site
`
`Nephrectomy + surgical
`metastasectomyd
`
`Relapse
`See First-Line
`Therapy (KID-3)
`
`Stage IV
`
`Potentially surgically
`resectable primarye with
`multiple metastatic sites
`
`Cytoreductive nephrectomy
`in select patients
`
`See First-Line
`Therapy (KID-3)
`
`Surgically unresectablee
`
`Tissue sampling
`
`See First-Line
`Therapy (KID-3)
`
`cSee Principles of Surgery (KID-A).
`dNo single follow-up plan is appropriate for all patients. Follow-up should be individualized based on patient requirements.
`eIndividualize treatment based on symptoms and extent of metastatic disease.
`
`KID-2
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0006
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`FIRST-LINE THERAPY
`(alphabetical by category and preference)
`Clinical trial
`or
`Pazopanib (category 1, preferred)
`or
`Sunitinib (category 1, preferred)
`or
`Bevacizumab + IFN (category 1)
`or
`Temsirolimus (category 1 for poor-
`prognosis patients,f category 2B for
`selected patients of other risk groups)
`or
`Axitinib
`or
`High-dose IL-2 for selected patientsg
`or
`Sorafenib for selected patients
`
`and
`Best supportive care:h
`See NCCN Guidelines for Palliative Care
`
`Follow-up
`(See KID-B)
`
`Predominant
`clear cell
`histology
`
`Relapse or
`Stage IV and
`surgically
`unresectable
`
`Non-clear cell
`histology
`
`See Systemic Therapy (KID-4)
`
`fPoor-prognosis patients, defined as those with ≥3 predictors of short survival.
`See Predictors of Short Survival Used to Select Patients for Temsirolimus (KID-C).
`gPatients with excellent performance status and normal organ function.
`hBest supportive care can include palliative RT, metastasectomy, bisphosphonates, or RANK ligand inhibitors for bony metastases.
`iIn clear cell and non-clear cell RCC with predominant sarcomatoid features, gemcitabine + doxorubicin (category 2B) and gemcitabine +
`sunitinib (category 2B) have shown benefit.
`jBased on the results of phase III trials, eligible patients should preferentially receive this agent over everolimus. See Discussion.
`
`SUBSEQUENT THERAPYi
`(alphabetical by category and preference)
`Clinical trial
`or
`Cabozantinib (category 1, preferred)j
`or
`Nivolumab (category 1, preferred)j
`or
`Axitinib (category 1)
`or
`Lenvatinib + everolimus (category 1)
`or
`Everolimus
`or
`Pazopanib
`or
`Sorafenib
`or
`Sunitinib
`or
`Bevacizumab (category 2B)
`or
`High-dose IL-2 for selected patientsg
`(category 2B)
`or
`Temsirolimus (category 2B)
`and
`Best supportive care:h
`See NCCN Guidelines for Palliative Care
`
`KID-3
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0007
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`Relapse or
`Stage IV and
`surgically
`unresectable
`
`Non-clear cell
`histology
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`Follow-up
`(See KID-B)
`
`SYSTEMIC THERAPYi,k
`(alphabetical by category and preference)
`Clinical trial (preferred)
`or
`Sunitinib (preferred)
`or
`Axitinib
`or
`Bevacizumab
`or
`Cabozantinib
`or
`Erlotinib
`or
`Everolimus
`or
`Lenvatinib + everolimus
`or
`Nivolumab
`or
`Pazopanib
`or
`Sorafenib
`or
`Temsirolimus (category 1 for poor-prognosis patients;f
`category 2A for other risk groups)
`
`and
`Best supportive care:h See NCCN Guidelines for Palliative Care
`
`fPoor-prognosis patients, defined as those with ≥3 predictors of short survival. See Predictors of Short Survival Used to Select Patients for Temsirolimus (KID-C).
`hBest supportive care can include palliative RT, metastasectomy, bisphosphonates, or RANK ligand inhibitors for bony metastases.
`iIn clear cell and non-clear cell RCC with predominant sarcomatoid features, gemcitabine + doxorubicin (category 2B) and gemcitabine + sunitinib (category 2B)
`have shown benefit.
`kPartial responses have been observed for cytotoxic chemotherapy (carboplatin + gemcitabine, carboplatin + paclitaxel, or cisplatin + gemcitabine) with collecting
`duct or medullary subtypes.
`
`KID-4
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0008
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`PRINCIPLES OF SURGERY
`• Nephron-sparing surgery (partial nephrectomy) is appropriate in selected patients, for example:
`Unilateral Stage I-III tumors where technically feasible
`Uninephric state, renal insufficiency, bilateral renal masses, and familial renal cell cancer
`
`• Open, laparoscopic, or robotic surgical techniques may be used to perform radical and partial nephrectomies.
`
`• Regional lymph node dissection is optional but is recommended for patients with adenopathy on preoperative imaging or palpable/
`visible adenopathy at time of surgery.
`
`• If adrenal gland is uninvolved, resection may be omitted.
`
`• Special teams may be required for extensive inferior vena cava involvement.
`
`• Observation or ablative techniques (eg, cryosurgery, radiofrequency ablation):
`Can be considered for selected patients with clinical stage T1 renal lesions.
`Biopsy of small lesions may be considered to obtain or confirm a diagnosis of malignancy and guide surveillance, cryosurgery, and
`radiofrequency ablation strategies.
`Randomized phase III comparison with surgical resection (ie, radical or partial nephrectomy by open or laparoscopic techniques)
`has not been done.
`Ablative techniques are associated with a higher local recurrence rate than conventional surgery.a,b
`
`• Generally, patients who would be candidates for cytoreductive nephrectomy prior to systemic therapy have:
`Excellent performance status (ECOG PS <2)
`No brain metastasis
`
`aCampbell SC, Novick AC, Belldegrun A, et al. Practice Guidelines Committee of the American Urological Association. Guideline for management of the clinical
`T1 renal mass. J Urol 2009;182:1271-1279.
`bKunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: A meta-analysis. Cancer 2008;113:2671-2680.
`
`KID-A
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0009
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`FOLLOW-UPa,b
`(category 2B)
`
`Stage I (pT1a)
`Follow-up During Active Surveillancec
`• H&P every 6 mo for 2 y, then annually up to 5 y after diagnosis
`• Comprehensive metabolic panel and other tests as indicated every 6 mo for first 2 y, then annually up to 5 y after diagnosis
`• Abdominal imaging:
`Abdominal CT or MRI within 6 mo of surveillance initiation, then CT, MRI, or US at least annually
`• Chest imaging:
`Chest x-ray or CT annually to assess for pulmonary metastases, if biopsy positive for RCC
`• Pelvic CT or MRI, as clinically indicated
`• CT or MRI of head or MRI of spine, as clinically indicated
`• Bone scan, as clinically indicated
`
`Follow-up After Ablative Techniquesc
`• H&P every 6 mo for 2 y, then annually up to 5 y after diagnosis
`• Comprehensive metabolic panel and other tests as indicated every 6 mo for first 2 y, then annually up to 5 y after diagnosis
`• Abdominal imaging:
`Abdominal CT or MRI at 3–6 mo following ablative therapy unless otherwise contraindicated then CT, MRI, or US annually for 5 y
`• Chest imaging:
`Chest x-ray or CT annually for 5 y for patients who have biopsy-proven low-risk RCC, nondiagnostic biopsies, or no prior biopsy
`• Repeat biopsy:
`New enhancement, a progressive increase in size of an ablated neoplasm, new nodularity in or around the treated zone, failure
`of the treated lesion to regress over time, satellite or port site lesions
`• Pelvic CT or MRI, as clinically indicated
`• CT or MRI of head or MRI of spine, as clinically indicated
`• Bone scan, as clinically indicated
`
`Continued on next page
`
`aDonat SM, Diaz M, Bishoff JT, et al. Follow-up for clinically localized renal neoplasms: AUA Guideline. J Urol 2013;190:407-416.
`bNo single follow-up plan is appropriate for all patients. Follow-up frequency and duration should be individualized based on patient requirements, and may be
`extended beyond 5 years at the discretion of the physician. Further study is required to define optimal follow-up duration.
`cImaging with contrast when clinically indicated.
`
`KID-B
` 1 of 4
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0010
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`FOLLOW-UPa,b
`(category 2B)
`
`Stage I (pT1a) and (pT1b)c
`Follow-up After a Partial or Radical Nephrectomy
`• H&P every 6 mo for 2 y, then annually up to 5 y after nephrectomy
`• Comprehensive metabolic panel and other tests as indicated every 6 mo for 2 y, then annually up to 5 y after nephrectomy
`• Abdominal imaging:
`After partial nephrectomy:
` ◊ Baseline abdominal CT, MRI, or US within 3–12 mo of surgery
` ◊ If the initial postoperative scan is negative, abdominal CT, MRI, or US may be considered annually for 3 y based on individual
`risk factors
`After radical nephrectomy:
` ◊ Patients should undergo abdominal CT, MRI, or US within 3–12 mo of surgery
` ◊ If the initial postoperative imaging is negative, abdominal imaging beyond 12 mo may be performed at the discretion of the
`physician
`• Chest imaging: Chest x-ray or CT annually for 3 y, then as clinically indicated
`• Pelvic CT or MRI, as clinically indicated
`• CT or MRI of head or MRI of spine, as clinically indicated
`• Bone scan, as clinically indicated
`
`Continued on next page
`
`aDonat SM, Diaz M, Bishoff JT, et al. Follow-up for clinically localized renal neoplasms: AUA Guideline. J Urol 2013;190:407-416.
`bNo single follow-up plan is appropriate for all patients. Follow-up frequency and duration should be individualized based on patient requirements, and
`may be extended beyond 5 years at the discretion of the physician. Further study is required to define optimal follow-up duration.
`cImaging with contrast when clinically indicated.
`
`KID-B
`2 of 4
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0011
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`FOLLOW-UPa,b
`(category 2B)
`
`Stage II or III
`Follow-up After a Radical Nephrectomyc
`• H&P every 3–6 mo for 3 y, then annually up to 5 y after radical nephrectomy and then as clinically indicated
`thereafter
`• Comprehensive metabolic panel and other tests as indicated every 6 mo for 2 y, then annually up to 5 y after
`radical nephrectomy, then as clinically indicated thereafter
`• Abdominal imaging:
`Baseline abdominal CT or MRI within 3–6 mo, then CT, MRI, or US (US is category 2B for Stage III),
`every 3–6 mo for at least 3 y and then annually up to 5 y
`Imaging beyond 5 y: as clinically indicated
`Site-specific imaging: as symptoms warrant
`• Chest imaging:
`Baseline chest CT within 3–6 mo after radical nephrectomy with continued imaging (CT or chest x-ray)
`every 3–6 mo for at least 3 y and then annually up to 5 y
`Imaging beyond 5 y: as clinically indicated based on individual patient characteristics and tumor risk factors
`• Pelvic CT or MRI, as clinically indicated
`• CT or MRI of head or MRI of spine, as clinically indicated
`• Bone scan, as clinically indicated
`
`Continued on next page
`
`aDonat SM, Diaz M, Bishoff JT, et al. Follow-up for clinically localized renal neoplasms: AUA Guideline. J Urol 2013;190:407-416.
`bNo single follow-up plan is appropriate for all patients. Follow-up frequency and duration should be individualized based on patient requirements, and
`may be extended beyond 5 years at the discretion of the physician. Further study is required to define optimal follow-up duration.
`cImaging with contrast when clinically indicated.
`
`KID-B
` 3 of 4
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0012
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`FOLLOW-UPd
`(category 2B)
`Follow-up for Relapsed or Stage IV and Surgically Unresectable Diseasec
`• H&P every 6–16 weeks for patients receiving systemic therapy, or more frequently as clinically indicated and adjusted for type of
`systemic therapy patient is receiving
`• Laboratory evaluation as per requirements for therapeutic agent being used
`• Chest, abdominal, and pelvic imaging:
`CT or MRI imaging to assess baseline pretreatment or prior to observation
`Follow-up imaging every 6–16 weeks as per physician discretion and per patient clinical status. Imaging interval to be adjusted
`upward and downward according to rate of disease change and sites of active disease
`• Consider CT or MRI of head at baseline and as clinically indicated. Annual surveillance scans at physician discretion
`• MRI of spine as clinically indicated
`• Bone scan as clinically indicated
`
`cImaging with contrast when clinically indicated.
`dNo single follow-up plan is appropriate for all patients. Follow-up should be individualized based on treatment schedules, side effects, comorbidities, and symptoms.
`
`KID-B
`4 of 4
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0013
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`PREDICTORS OF SHORT SURVIVAL USED TO SELECT PATIENTS FOR TEMSIROLIMUSa
`
`Poor-prognosis patients are defined as those with ≥3 predictors of short survival.
`• Lactate dehydrogenase level >1.5 times upper limit of normal
`• Hemoglobin level < lower limit of normal
`• Corrected serum calcium level >10 mg/dL (2.5 mmol/liter)
`• Interval of less than a year from original diagnosis to the start of systemic therapy
`• Karnofsky performance score ≤70
`• ≥2 sites of organ metastasis
`
`aHudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-2281.
`
`KID-C
`
`NCCN Guidelines Version 1.2017
`Kidney Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 1.2017, 09/26/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1091-0014
`
`

`
`Printed by M Ratain on 10/30/2016 3:48:35 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Version 1.2017 Staging
`Kidney Cancer
`
`NCCN Guidelines Index
`Table of Contents
`Discussion
`
`Table 1
`American Joint Committee on Cancer (AJCC)
`TNM Staging System for Kidney Cancer (7th ed., 2010)
`Primary Tumor (T)
`TX
`Primary tumor cannot be assessed
`T0
`No evidence of primary tumor
`T1
`Tumor 7 cm or less in greatest dimension, limited to the kidney
`T1a
`Tumor 4 cm or less in greatest dimension, limited to the kidney
`T1b
` Tumor more than 4 cm but not more than 7 cm in greatest
`dimension, limited to the kidney
`Tumor more than 7 cm in greatest dimension, limited to the kidney
` Tumor more than 7 cm but less than or equal to 10 cm in greatest
`dimension, limited to the kidney
`T2b Tumor more than 10 cm, limited to the kidney
`T3
` Tumor extends into major veins or perinephric tissues but not into
`the ipsilateral adrenal gland and not beyond Gerota’s fascia
` Tumor grossly extends into the renal vein or its segmental (muscle
`containing) branches, or tumor invades perirenal and/or renal sinus
`fat but not beyond Gerota’s fascia
`T3b Tumor grossly extends into the vena cava below the diaphragm
`T3c
` Tumor grossly extends into the vena cava above the diaphragm or
`invades the wall of the vena cava
` Tumor invades beyond Gerota’s fascia (including contiguous
`extension into the ipsilateral adrenal gland)
`
`T4
`
`T2
`T2a
`
`T3a
`
`Regional Lymph Nodes (N)
`NX Regional lymph nodes cannot be assessed
`N0 No regional lymph node metastasis
`N1 Metastasis in regional lymph node(s)
`
`Distant Metastasis (M)
`M0 No distant metastasis
`M1 Distant metastasis
`
`Anatomic Stage/Prognostic Groups
`Stage I
`T1
` N0
`M0
`
`Stage II
`
`T2
`
` N0
`
`M0
`
`M0
`Stage III T1 or T2 N1
` T3 N0 or N1 M0
`
`Stage IV T4 Any N M0
` Any T A