Using PET/CT in Prostate Cancer

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Purpose and Audience

Provide urologists, surgeons, medical oncologists,

radiation oncologists and other prostate cancer

specialists with the following information to aid in the

diagnosis and management of prostate cancer patients

A summary of PET radiopharmaceuticals that are FDA-

approved to image prostate cancer

NCCN Practice Guidelines updates for using PET/CT in

prostate cancer

Recent Report from the National Oncologic

PET Registry (NOPR)

Impact on patient management

PET/CT in Prostate Cancer

PET/CT plays an important role in the evaluation of

prostate cancer on many levels

Detecting metastatic disease

Restaging

Biochemical relapse post-radical therapy

A biochemical relapse is one where, after completing treatment

(e.g., prostatectomy), PSA begins rising again but the cancer

cannot (yet) be detected by CT or MRI

Treatment monitoring

Use for primary staging generally limited to only high-risk

disease

Jadvar H. J Nucl Med 2013; 54(10):1685-1688

FDA-Approved PET Radiopharmaceuticals

for Prostate Cancer

Tracers that image metabolism

C-11 choline and F-18 fluciclovine

Used to localize disease recurrence in men who have

rising PSA and inconclusive conventional imaging

F-18 FDG

Used typically in patients with late-stage recurrent prostate

cancer and elevated PSA

Tracers that image bone

F-18 NaF (sodium fluoride)

Used to detect bone metastases

PET/CT in Prostate Cancer:

NCCN Guidelines

C-11 choline: Radioactive diagnostic agent for PET imaging of

patients with suspected prostate cancer recurrence and non-

informative bone scintigraphy, CT or MRI. In these patients, C-11

choline-PET/CT imaging may help identify potential sites of prostate

cancer recurrence for subsequent histologic confirmation

F-18 NaF: Newer technology using F-18 NaF for PET scanning can

be used as a diagnostic staging study; appears to have greater

sensitivity than Tc-99m bone scan for assessing bone metastasis

F-18 FDG: In certain clinical settings, the use of F-18 FDG may

provide useful information; F-18 FDG-PET/CT should not be used

routinely since data on its utility in prostate cancer is limited

F-18 fluciclovine: Indicated for PET imaging with suspected

prostate cancer recurrence based on elevated blood PSA levels

following prior treatment.

www.NCCN.org NCCN Guidelines Prostate Cancer, Version 1.2016 accessed 3/8/16

(NOTE: FDA approved fluciclovine May 2016; it is

not yet included in the NCCN guidelines.)

Cancer Guidelines: Overview for

Prostate Cancer Evaluation

The NCCN guidelines have specific recommendations when using PET/CT

imaging in prostate cancer: (1) primary disease, (2) biochemical recurrence and

(3) advanced disease. Below is a sample of information taken from these

guidelines. Please consult the NCCN website for their complete set of

guidelines. www.NCCN.org/prostate cancer guidelines accessed 3/8/16

PET/CT in Prostate Cancer:

Benefits of C-11 Choline Imaging

CMS may reimburse the use of C-11 choline-PET/CT in

biochemical failure (i.e., relapse of prostate cancer with

inconclusive bone scan, CT and/or MRI)

Contact your local MAC for your area’s coverage decision

Established tracer to identify progression to support

more appropriate treatment options

Shows soft tissue and osseous metastatic disease

Availability varies due to half-life of 20 minutes

Ceci F, et al. EJNMMI 2014; 41(12):2222-2231

CASE EXAMPLE: 74-year-old male with history of prostate

cancer and definitive therapy now presenting with

biochemical recurrence; CT and bone scan were negative.

PET/CT in Prostate Cancer:

Benefits of C-11 Choline Imaging

Results: C-11 choline-PET/CT revealed both soft tissue and

osseous multifocal metastases

R R R L L L

PET/CT in Prostate Cancer:

C-11 Choline Imaging Data

Recent publication: Ceci et al. 2014

150 patients with recurrent prostate cancer

Subjects having C-11 choline-PET/CT imaging resulted

in 46.7% overall treatment change

14% did not undergo radiation due to distant mets

18% had a major clinical change (note: paper did not

provide information on the reported change)

Ceci F, et al. EJNMMI 2014; 41(12):2222-2231

PET/CT in Prostate Cancer:

Benefits of F-18 NaF Imaging

SPECT PET/CT

Even-Sapir E, et al. J Nucl Med 2006; 47:287–297

F-18 NaF-PET/CT has higher sensitivity and specificity

than planar or SPECT bone scan using Tc-99m

Study compared planar and SPECT bone scan to F-18

NaF imaging in 44 patients with high-risk prostate cancer

23 (52%) had bone metastases

Test Sensitivity Specificity

Planar bone scan 70% 57%

Multi FOV SPECT 92% 82%

F-18 NaF-PET/CT 100% 100%

PET/CT in Prostate Cancer:

F-18 NaF Imaging Data

Even-Sapir E, et al. J Nucl Med 2006; 47:287–297

The National Oncologic PET Registry (NOPR) is a

mechanism for CMS Coverage

A registry for F-18 NaF-PET to identify bone metastasis

similar to that now in place for F-18 FDG-PET

Launched February 7, 2011

>30,000 scans with complete data submitted to date

PET/CT in Prostate Cancer:

F-18 NaF and NOPR

Hillner B, et al. J Nucl Med 2014; 55:574-581

F-18 NaF-PET changed intended management in 77%

of cases

Initial no treatment decision revised to treatment in 77%

Switch from initial staging [IS] to primary osseous

metastization [POM]

Therapy management changed in 44% to 52%

Consideration for coverage request for F-18 NaF still

under evaluation by CMS

Hillner B, et al. J Nucl Med 2014; 55:574-581

Impact of F-18 NaF on Prostate

Cancer Management

PET/CT in Prostate Cancer Recurrence:

Imaging with F-18 Fluciclovine

Emission image at 0.12h in healthy

adult volunteer following IV

administration of F-18 fluciclovine (McParland B, et al. EJNMMI 2013; 40(8):1256–1264)

PET (A) and PET/CT (B) image of fluciclovine in

man with biopsy-proven recurrence in the

prostate bed (Schuster et al. J Nucl Med 2007; 48:56–63)

The color scale ranges from radiotherapy dose of 0 to 77 Gy.

F-18 fluciclovine imaging can be used to plan

radiotherapy treatment

PET/CT in Prostate Cancer:

Image-Guided Radiotherapy Planning

Schreibmann E, et al. Int J Rad Onco 2016

A. Original radiotherapy

(Rx) treatment plan B. Fluciclovine imaging

results reveal iliac lymph

node involvement

C. Revised treatment plan

now includes involved LN

A B C

Impact of Prostate Cancer Imaging

on Disease Management

Change in management: a summary review of clinical

studies and the literature

C-11 choline-PET/CT1

7% in overall treatment change

18% in major changes

F-18 fluciclovine-PET/CT imaging in subjects undergoing

salvage radiotherapy treatment planning2

F-18 fluciclovine results changed planning volumes for 46/55

abnormalities: 28(51%) in the lymph nodes, 11(20%) in the

prostate bed, 10(18%) in the prostate and 6(11%) in the seminal

vesicles

1. Ceci F, et al. EJNMMI 2014; 41(12):2222-2231

2. Schreibmann E, et al. J Rad Onc Biol Phys 2016, doi:

10.1016/j.ijrobp.2016.04.023

Impact of Prostate Cancer Imaging

on Disease Management

Change in management: a summary review of clinical

studies and the literature (cont.)

F-18 NaF3,4

In specificity and sensitivity vs planar bone scan and multi-FOV

SPECT

In recognition of bone metastases for high-risk prostate cancer

patients (52%)

In intended management of NOPR patients (77%)

In changes in therapy management (44% to 52%)

3. Even-Sapir E, et al. J Nucl Med 2006; 47:287-297

4. Hillner B, et al. J Nucl Med 2014; 55:574-581

Key Messages

PET/CT is a powerful non-invasive diagnostic tool

Effective for: Detecting metastatic disease, restaging, identifying

biochemical relapse post-radical therapy, monitoring treatment

and primary staging generally limited to only high-risk disease

F-18 NaF imaging is an important tool for evaluating bone mets

Indications for using PET/CT in prostate cancer patients

Negative CT/MRI/SPECT bone scan and rising PSA

Radiation therapy planning

Staging of aggressive tumor types

F-18 FDG and F-18 fluciclovine show utility in detecting

local and/or regional and distant recurrence

References

www.NCCN.org Prostate Cancer Guidelines v.1.2016 accessed 3/8/16

Ceci F, Herrmann K, Castellucci P, et al. Impact of 11C-choline PET/CT on

clinical decision making in recurrent prostate cancer: results from a

retrospective two-centre trial. EJNMMI Dec 2014; 41(12):2222-2231

Even-Sapir, E. Imaging of Malignant Bone Involvement by morphologic,

scintigraphic, and hybrid modalities. J Nuc Med 2005; 46:1356-1367

Even-Sapir E, Metser U, Mishani E, et al. The detection of bone metastases

in patients with high-risk prostate cancer: 99mTc-MDP planar bone

scintigraphy, single- and multi-Field-of-View SPECT, 18F-fluoride PET, and

18F-fluoride PET/CT. J Nucl Med 2006; 47:287–297

References

Frederick DG, Fahey FH, Packard AB, et al. Skeletal PET with 18F-fluoride:

Applying new technology to an old tracer. J Nucl Med 2008; 49:68–78

Hillner B, Siegel B, Hanna L, et al. Impact of 18F-Fluoride PET in patients

with known prostate cancer: Initial results from the National Oncologic PET

Registry. J Nucl Med 2014; 55:574-581

Jadvar H. Molecular Imaging of Prostate Cancer with PET. J Nucl Med

2013; 54(10):1685-1688

McParland B, Wall A, Johansson S, and Sørensen J. The clinical safety,

biodistribution and internal radiation dosimetry of [18F]fluciclovine in healthy

adult volunteers. EJNMMI 2013; 40(8):1256–1264

Segall G, Delbeke D, Stabin M, et al. SNMMI Practice Guidelines for

Sodium 18F-Fluoride PET/CT Bone Scans 1.1. JNMMI 2010; 51(11):1813-

1820

References

Schirrmeister H, Guhlmann A, Kotzerke J,et al. Early detection and accurate

description of extent of metastatic bone disease in breast cancer with

fluoride ion and positron emission tomography. J Clin Oncol 1999;

17(8):2381-2389a

Schuster D, Votaw J, Nieh P, et al. Initial experience with the radiotracer

anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in

prostate carcinoma. J Nucl Med 2007; 48:56–63

Important Safety Information

Image interpretation errors can occur with PET imaging. A negative image

does not rule out recurrent prostate cancer and a positive image does not

confirm its presence. Clinical correlation, which may include

histopathological evaluation, is recommended.

The performance of F-18 fluciclovine and C-11 choline seem to be affected

by PSA levels. For F-18 fluciclovine, uptake may occur with other cancers

and benign prostatic hypertrophy in primary prostate cancer.

Hypersensitivity reactions, including anaphylaxis, may occur in patients who

receive PET radiopharmaceuticals. Emergency resuscitation equipment and

personnel should be immediately available.

PET/CT imaging contributes to a patient’s overall long-term cumulative

radiation exposure, which is associated with an increased risk of cancer.

Safe handling practices should be used to minimize radiation exposure to

the patient and healthcare providers.

Adverse reactions, although uncommon, may occur when using PET

radiopharmaceuticals. Always refer to the package insert prior to use.