i3 Health is pleased to make the Clinician's Resource Guide from this activity available for use as a nonaccredited self-study or teaching resource.

1. Clinical Tools and Resources for
Self-Study and Patient Education
CASTRATION-RESISTANT PROSTATE CANCER
REFERENCE GUIDE
The clinical tools and resources contained herein are provided as educational adjuncts
to the CME/CE-certified online activity Current Trends in the Management of
Castration-Resistant Prostate Cancer. To access the activity and earn CME/CE credit,
visit:
https://www.i3Health.com/
CONTENTS
I: TNM Staging of Prostate Tumors..................................................................................2
II: NCCN Guidelines for Systemic Therapy: M0 CRPC.....................................................4
III: NCCN Guidelines for Systemic Therapy: M1 CRPC....................................................5
IV: NCCN Guidelines for Subsequent Systemic Therapy: M1 CRPC ...............................6
V: NCCN Guidelines for Systemic Therapy: Additional Options for M1 CRPC................7
VI: Principles of Androgen Deprivation Therapy..............................................................8
VII: Glossary of Systemic Treatments for Prostate Cancer .............................................10
VIII: Common Terminology Criteria for Adverse Events (CTCAE): Osteoporosis ..........11
IX: Managing Treatment-Related Adverse Events: Osteoporosis..................................12

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I: TNM STAGING OF PROSTATE TUMORS
TNM Clinical Classifications
TNM Stage Definition
T1
Tumor cannot be felt or seen with imaging tests. Found in tissue
removed by biopsies or surgical treatments (incidental finding)
T1a Incidental cancer found in £5% of removed tissue
T1b Incidental cancer found in >5% of removed tissue
T1c Tumors found by needle biopsy done as a result of high PSA level
T2
Tumors felt during digital rectal exams. Cancer growth within the
lobes (left and right halves of the prostate); hasn’t grown outside the
prostate gland
T2a Tumors have not grown beyond half of one lobe
T2b Tumors have grown beyond half of one lobe but not to the other lobe
T2c Tumors have grown into both lobes
T3
Tumors have spread outside the prostate, reaching connective tissue
around the prostate, the seminal vesicles, or the neck of the bladder
T3a
Tumors have grown outside the prostate but not into the seminal
vesicles
T3b Tumors have grown outside the prostate and into the seminal vesicles
T4
Tumors have fixed or invaded other nearby tissues such as the external
sphincter, rectum, bladder, levator muscles, or pelvic wall
TNM = tumor/nodes/metastases; PSA = prostate-specific antigen.

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TNM Clinical Classifications (Cont.)
TNM Stage Definition
NX Unknown if cancer is in lymph nodes
N0 No cancer within nearby lymph nodes
N1 Cancer has spread into nearby lymph nodes
MX Unknown if cancer has spread to distant sites
M0 No growth to distant sites
M1 Cancer has spread to distant sites
M1a Cancer has spread to non-regional lymph nodes
M1b Cancer has spread to distant bones
M1c Cancer has spread to distant organs
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: prostate cancer. Version
4.2018. Available at http://www.nccn.org

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II: NCCN GUIDELINES FOR SYSTEMIC THERAPY: M0 CRPC
All recommendations are category 2A unless otherwise indicated.
CRPC = Castration-resistant prostate cancer; PSADT = prostate-specific antigen doubling time; mo = months.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: prostate cancer. Version
4.2018. Available at http://www.nccn.org

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III: NCCN GUIDELINES FOR SYSTEMIC THERAPY: M1 CRPC
All recommendations are category 2A unless otherwise indicated.
MSI-H = microsatellite instability high; dMMR = deficient mismatch repair; RT = radiotherapy.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: prostate cancer. Version
4.2018. Available at http://www.nccn.org

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IV: NCCN GUIDELINES FOR SUBSEQUENT SYSTEMIC THERAPY:
M1 CRPC
All recommendations are category 2A unless otherwise indicated.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: prostate cancer. Version
4.2018. Available at http://www.nccn.org

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V: NCCN GUIDELINES FOR SYSTEMIC THERAPY: ADDITIONAL
OPTIONS FOR M1 CRPC
All recommendations are category 2A unless otherwise indicated.
MRI = magnetic resonance imaging.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: prostate cancer. Version
4.2018. Available at http://www.nccn.org

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VI: PRINCIPLES OF ANDROGEN DEPRIVATION THERAPY
Indication Treatments
ADT for regional disease, adjuvant
treatment of lymph node
metastases, or patients on
observation who require treatment
• Orchiectomy
• LHRH agonist alone
o Goserelin, histrelin, leuprolide, or triptorelin
Neoadjuvant, concurrent, and/or
adjuvant ADT as part of radiation
therapy for clinically localized
disease
• LHRH agonist alone
o Goserelin, histrelin, leuprolide, or triptorelin
• LHRH agonist (as above) plus a first-generation
antiandrogen
o Nilutamide, flutamide, or bicalutamide
ADT for M0 or M1 castration-naive
disease
• Orchiectomy
• LHRH agonist alone (first-generation antiandrogen
must be given for ³7 days to prevent testosterone
flare if metastases are present in weight-bearing
bone)
• Goserelin, histrelin, leuprolide, or triptorelin
• LHRH agonist (as above) plus first-generation
antiandrogen
• Nilutamide, flutamide, or bicalutamide
• LHRH antagonist
• Degarelix
• Orchiectomy, LHRH agonist, or LHRH antagonist (as
above) plus abiraterone plus prednisone or
abiraterone with methylprednisolone (category 2B)
(for M1)

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Indication (Cont.) Treatments
Secondary hormone therapy for
M0 or M1 CRPC
• Continue LHRH agonist or antagonist to maintain
castrate serum levels of testosterone (<50 ng/dL) and
add:
o Second-generation antiandrogen
o First-generation antiandrogen
§ Apalutamide (for M0)
§ Enzalutamide (for M0 or M1)
o First-generation antiandrogen
§ Nilutamide, flutamide, or bicalutamide
o Ketoconazole
o Ketoconazole plus hydrocortisone
o Corticosteroids
§ Hydrocortisone, prednisone,
dexamethasone
o DES or other estrogen
All recommendations are category 2A unless otherwise indicated.
DES = diethylstilbestrol.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: prostate cancer. Version
4.2018. Available at http://www.nccn.org

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VII: GLOSSARY OF SYSTEMIC TREATMENTS
Agent Definition
Abiraterone (Zytiga®
)
Androgen biosynthesis inhibitor. Blocks CYP17 (enzyme
that produces testosterone)
Apalutamide (ErleadaÔ)
Androgen receptor inhibitor; decreases testosterone.
Used for M0 CRPC resistant to ADT
Cabazitaxel (Jevtana®
) Microtubule inhibitor; interferes with the cell division
Denosumab (Prolia®
, Xgeva®
)
Monoclonal antibody that binds to RANKL, a protein
involved in the growth and survival of osteoclasts (cells
that disintegrate bone). Stops osteoclasts from forming
Docetaxel (Taxotere®
, Docefrez®
) Stops or slows growth of cancer cells in the body
Enzalutamide (Xtandi®
)
Androgen receptor inhibitor for M0/M1 CRPC. Used in
patients who no longer respond to hormone therapy to
lower testosterone. Reduces risk of metastasis
Leuprolide (Eligard®
, Lupron
Depot®
, Viadur®
)
Works as a gonadotropin-releasing hormone (GnRH) to
reduce testosterone levels
Mitoxantrone (Novantrone®
) Antitumor antibiotic
Pembrolizumab (Keytruda®
)
Monoclonal antibody; checkpoint inhibitor blocking the
PD-1 pathway
Prednisone, methylprednisolone
Steroids used to treat pain, inflammation, and edema.
Have been shown to decrease PSA levels in M1 CRPC
Radium-223 (Xofigo®
) Alpha particle-emitting drug to treat bone metastases
Sipuleucel-T (Provenge®
) Autologous active cellular immunotherapy M1 CRPC
Chemotherapy combinations
Cisplatin/etoposide
Carboplatin/etoposide
Docetaxel/carboplatin
Cancer Treatment Centers of America (2017). Prostate cancer drug information. Available at
https://www.cancercenter.com
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: prostate cancer. Version
4.2018. Available at http://www.nccn.org

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VIII: COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS
(CTCAE): OSTEOPOROSIS
CTCAE Term Grade 1 Grade 2 Grade 3 Grade 4
Osteoporosis
Radiologic
evidence of
osteoporosis or
BMD T-score of -
1 to -2.5
(osteopenia)
BMD T-score
<-2.5; loss of
height <2 cm;
limited
instrumental
ADL. Therapy to
improve BMD
indicated.
Loss of height ≥2
cm; limited self-
care ADL.
Hospitalization
indicated.
—
National Cancer Institute (2017). Common terminology criteria for adverse events (CTCAE). Version 5.2017.
Available at https://ctep.cancer.gov

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IX: MANAGING TREATMENT-RELATED ADVERSE EVENTS:
OSTEOPOROSIS
Osteoporosis
Risk Factors
• Hormone deprivation therapy
• Being thin or having a small frame
• Having a family history of the disease
• Using certain medications, such as glucocorticoids
• Not getting enough calcium
• Not getting enough physical activity
• Smoking
• Drinking too much alcohol
Management
• Medication
• Alendronate (BinostoÒ, FosamaxÒ)
• Pamidronate (ArediaÒ) and zoledronic acid
(ZometaÒ)
• Denosumab (Prolia®, Xgeva®)
• Nutrition (diet high in vitamin D and calcium)
• Exercise
• Healthy lifestyle (no smoking, moderate drinking)
• Bone mineral density (BMD) test
• Central dual-energy x-ray absorptiometry
(DEXA)
American Society of Clinical Oncology (2012). Hormone deprivation symptoms in men. Available at
http://www.cancer.net
National Institute of Arthritis and Musculoskeletal and Skin Diseases (2016). What prostate cancer survivors need to
know about osteoporosis. Available at http://www.bones.nih.gov