Coverage Policy Manual
Policy #: 2001035
Category: Radiology
Initiated: December 1999
Last Review: November 2023
  PET or PET/CT for Prostate Cancer, FDG and non-FDG
Description:
Note:  This policy is intended for those members with contracts that do not have requirements for prior approval for imaging procedures through an independent imaging review organization.
 
Positron Emission Tomography (PET) imaging uses radiotracers that can reveal both anatomical and physiological information. A variety of tracers are used for positron emission tomography (PET) scanning, including oxygen-15, nitrogen-13, carbon-11 choline, and fluorine-18. In 2016, 2 additional tracers, gallium-68, and fluciclovine-18, were approved by the Food and Drug Administration (FDA). Because of their short half-life, some tracers must be made locally using an onsite cyclotron. For certain malignancies PET scans have been shown to be more accurate than other non-invasive tests in detecting malignant disease.  However, as with all diagnostic tests, PET scans do not detect cancer 100% of the time that cancer is present (a false negative test),nor do all positive PET scans represent the presence of malignant disease (a false positive test).  A false negative test may occur because a critical volume of malignant cells is necessary for a PET scan to be positive. PET scans may be false positive in the presence of inflammation or granulomatous disease.
 
The reported sensitivity of scanning with the radiotracer FDG varies between only 4% and 64% in the studies reported on carcinoma of the prostate.
 
Choline C 11 Injection is a radioactive diagnostic agent for PET imaging to assist in the diagnosis of recurrent prostate cancer in patients with non-informative conventional imaging (bone scintigraphy, computerized tomography [CT], or magnetic resonance imaging [MRI]).  Suspected prostate recurrence is based upon elevated blood prostatic antigen (PSA) levels following initial therapy.
 
Definitions
 
Screening – testing in the absence of an established or clinically suspected diagnosis
 
Diagnosis - testing based on a reasonable clinical suspicion of a particular condition or disorder
 
Diagnostic Workup – initial staging of documented malignancy
 
Management – testing to direct therapy of an established condition, which may include preoperative or postoperative imaging, or imaging performed to evaluate the response to nonsurgical intervention. In oncologic imaging, management applies to patients with measurable disease and to imaging performed before or after planned treatment intervention, therapy response, restaging or clinically suspected recurrence.
 
Surveillance – periodic assessment following completion of therapy. In oncologic imaging, surveillance applies to asymptomatic patients in remission and/or without measurable disease
 
Cannot be performed or is nondiagnostic – applies when the test:
    • Is positive or indeterminate for clinically significant pathology when the information provided about the abnormality by the test is not sufficient to direct subsequent management
    • Is negative when the negative likelihood ratio of the test is both insufficient to confidently exclude the absence of suspected disease and unable to direct subsequent management. This typically applies in scenarios with moderate to high clinical pretest probability with negative testing or low pretest probability with clear evidence for net benefit
    • Has been previously nondiagnostic because of a persistent clinical factor (e.g., body habitus, immobility) that is very likely to make retesting nondiagnostic as well Cannot be performed due to a medical contraindication (e.g., contrast nephrotoxicity, allergy, or in highly radiation sensitive populations such as pediatrics and pregnancy) or reasonable unavailability related to lack of local expertise or service availability
Standard or conventional imaging: Refers to imaging that does not require a PET/CT. Depending on the clinical scenario and individual patient circumstances, this may include computed tomography, magnetic resonance imaging, ultrasound and/or scintigraphy.
Policy/
Coverage:
Effective April 14, 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Positron emission tomography (PET) scanning for patients with recurrent/persistent prostate cancer meets primary coverage criteria for effectiveness (may be considered medically necessary) and is covered for:
18F Fluciclovine PET/CT or 11C Choline PET/CT
 
Management of Recurrent/Persistent disease
Indicated when ALL of the following criteria are met:
        • Original clinical stage T1-T3 and NX or N0 treated with prostatectomy and/or radiation therapy, with biochemically recurrent/persistent disease (see note #1 for definition); and
        • Negative or nondiagnostic imaging within past 60 days, based on most recent PSA value (if applicable):
            • PSA < 1 ng/ml and rising: Prostate/Pelvic MRI (within past 60 days)
            • PSA > 10 ng/ml: Any conventional imaging (see note #2 for imaging list) within past 60 days; and
        • Patient is a candidate for curative intent salvage therapy (see note #3 for definition); and
        • PET/CT with 18F Fluciclovine or 11C Choline has not been performed within the past 3 months
 
68Ga Prostate-specific membrane antigen (PSMA) PET/CT or 18Flabeled radiotracers targeting prostate specific membrane antigen (PSMA) PET/CT
 
Diagnostic Workup
        • Indicated for unfavorable intermediate or high-risk disease with equivocal or nondiagnostic conventional imaging, (see note #2 for imaging list) when confirmation may inform decisions about prostatectomy and/or radiation therapy
 
Management of Recurrent/Persistent disease
Indicated in EITHER of the following scenarios:
        • When ALL of the following criteria are met:
            • Original clinical stage T1-T3 and NX or N0 treated with prostatectomy and/or radiation therapy, with biochemically recurrent/persistent disease (see note #1 for definition); and
            • Negative or nondiagnostic conventional imaging (see note #2 for imaging list) within past 60 days if PSA > 10 ng/ml
            • Patient is a candidate for curative intent salvage therapy (see note #3 for definition); and
            • PET/CT has not been performed within the past 3 months
OR
        • Evaluation of metastatic castrate-resistant disease for radioligand therapy when previously treated with taxane-based chemotherapy AND ANY of the following androgen-receptor pathway inhibitors:
            • Abiaterone
            • Apalutamide
            • Enzalutamide
            • Darolutamide
Notes:
        1. Biochemical recurrence/persistence” definition depends on prior treatment:
            • Post-prostatectomy (PSA should be 0 after surgery):
                • Persistence: Detection of a PSA higher than 0 within the first three months after surgery
                • Recurrence: PSA initially undetectable, then rising PSA > 0.2 ng/ml, with a second confirmatory level > 0.2 ng/mL (American Urological Association definition)
            • Post-radiation therapy:
                • Recurrence: rise by > 2 ng/mL above the nadir PSA (Radiation Therapy Oncology Group-American Society of Therapeutic Radiology and Oncology (RTOG-ASTRO) Phoenix Consensus)
2. Conventional imaging: CT Abdomen/Pelvis (MRI if CT contraindicated) or MRI or bone scan. Conventional imaging not required for low-risk disease (T1-T2a, PSA < 10 ng/ml, and Gleason < 6/Group 1).
3. External beam radiation therapy +/- androgen deprivation therapy after prostatectomy OR radical prostatectomy, cryosurgery, high intensity focused ultrasound, or brachytherapy after external beam radiation therapy
 
For all fully insured contracts, all self-funded church-sponsored health plans and all self-funded government-sponsored health plans other than the Arkansas State and Public School Employees program, the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET scanning for patients with prostate cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • FDG-PET/CT scanning
    • Surveillance*
 
For members with contracts without primary coverage criteria, PET scanning for patients with Prostate Cancer is considered investigational and is not covered for any indication or any circumstance other than those listed above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
*For all fully insured contracts, all self-funded church-sponsored health plans and all self-funded government-sponsored health plans other than the Arkansas State and Public School Employees program, the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Effective April 09, 2023 - April 13, 2024
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Positron emission tomography (PET) scanning for patients with recurrent/persistent prostate cancer meets primary coverage criteria for effectiveness (may be considered medically necessary) and is covered for:
18F Fluciclovine PET/CT or 11C Choline PET/CT
 
Management of Recurrent/Persistent disease
Indicated when ALL of the following criteria are met:
        • Original clinical stage T1-T3 and NX or N0 treated with prostatectomy and/or radiation therapy, with biochemically recurrent/persistent disease (see note #1 for definition); and
        • Negative or nondiagnostic imaging within past 60 days, based on most recent PSA value (if applicable):
            • PSA < 1 ng/ml and rising: Prostate/Pelvic MRI (within past 60 days)
            • PSA > 10 ng/ml: Any conventional imaging (see note #2 for imaging list) within past 60 days; and
        • Patient is a candidate for curative intent salvage therapy (see note #3 for definition); and
        • PET/CT with 18F Fluciclovine or 11C Choline has not been performed within the past 3 months
 
68Ga Prostate-specific membrane antigen (PSMA) PET/CT or 18F-DCFPyL (piflufolastat or Pylarify) PET/CT
 
Management of Recurrent/Persistent disease
Indicated in EITHER of the following scenarios:
        • When ALL of the following criteria are met:
            • Original clinical stage T1-T3 and NX or N0 treated with prostatectomy and/or radiation therapy, with biochemically recurrent/persistent disease (see note #1 for definition); and
            • Negative or nondiagnostic conventional imaging (see note #2 for imaging list) within past 60 days if PSA > 10 ng/ml
            • Patient is a candidate for curative intent salvage therapy (see note #3 for definition); and
            • PET/CT has not been performed within the past 3 months
OR
        • Metastatic castrate-resistant disease previously treated with androgen receptor pathway inhibition and taxane-based chemotherapy, prior to planned treatment with radioligand therapy.
Notes:
        1. Biochemical recurrence/persistence” definition depends on prior treatment:
            • Post-prostatectomy (PSA should be 0 after surgery):
                • Persistence: Detection of a PSA higher than 0 within the first three months after surgery
                • Recurrence: PSA initially undetectable, then rising PSA > 0.2 ng/ml, with a second confirmatory level ≥ 0.2 ng/mL (American Urological Association definition)
            • Post-radiation therapy:
                • Recurrence: rise by > 2 ng/mL above the nadir PSA (Radiation Therapy Oncology Group-American Society of Therapeutic Radiology and Oncology (RTOG-ASTRO) Phoenix Consensus)
2. Conventional imaging: CT Abdomen/Pelvis (MRI if CT contraindicated) or MRI or bone scan. Conventional imaging not required for low-risk disease (T1-T2a, PSA < 10 ng/ml, and Gleason < 6/Group 1).
3. External beam radiation therapy +/- androgen deprivation therapy after prostatectomy OR radical prostatectomy, cryosurgery, high intensity focused ultrasound, or brachytherapy after external beam radiation therapy  
For all fully insured contracts, all self-funded church-sponsored health plans and all self-funded government-sponsored health plans other than the Arkansas State and Public School Employees program, the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
PET scanning for patients with prostate cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • FDG-PET/CT scanning
    • Diagnostic Workup and Diagnosis
    • Surveillance*
 
For members with contracts without primary coverage criteria, PET scanning for patients with Prostate Cancer is considered investigational and is not covered for any indication or any circumstance other than those listed above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
*For all fully insured contracts, all self-funded church-sponsored health plans and all self-funded government-sponsored health plans other than the Arkansas State and Public School Employees program, the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Effective November 06, 2022 to April 08, 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Positron emission tomography (PET) scanning for patients with recurrent prostate cancer meets primary coverage criteria for effectiveness and is covered for:
18F Fluciclovine PET/CT or 11C Choline PET/CT
 
Management (of treatment or disease)
Indicated when ALL of the following criteria are met:
        • Original clinical stage T1-T3 and NX or N0 treated with prostatectomy and/or radiation therapy, with biochemically recurrent/persistent disease (1); and
        • Results of conventional imaging (2) performed within the past 60 days are negative for metastasis; and
        • Patient is a candidate for curative intent salvage therapy (3); and
        • PSA level is > 1 ng/ml; OR PSA is rising and prostate MRI cannot be performed or is nondiagnostic
        • PET/CT with 18F Fluciclovine or 11C Choline has not been performed within the past 3 months
68Ga Prostate-specific membrane antigen (PSMA) PET/CT or 18F-DCFPyL (piflufolastat or Pylarify) PET/CT
 
Management (of treatment or disease)
Indicated in EITHER of the following scenarios:  
        • When ALL of the following criteria are met:
            • Original clinical stage T1-T3 and NX or N0 treated with prostatectomy and/or radiation therapy, with biochemically recurrent/persistent disease (1); and
            • Results of conventional imaging (2) performed within the past 60 days are negative for metastasis; and
            • Patient is a candidate for curative intent salvage therapy (3); and
            • PSA level is > 1 ng/ml or PSA is rising; and
            • PET/CT has not been performed within the past 3 months;OR
        • Metastatic castrate-resistant disease previously treated with androgen receptor pathway inhibition and taxane-based chemotherapy, prior to planned treatment with radioligand therapy
 
Notes:
        1. Post-prostatectomy (PSA should be 0 after surgery):
Persistence: Detection of a PSA higher than 0 within the first three months after surgery; Recurrence: PSA initially undetectable, then rising PSA > 0.2 ng/ml, with a second confirmatory level ≥ 0.2 ng/mL (American Urological Association definition)
Post-radiation therapy:
Recurrence: rise by > 2 ng/mL above the nadir PSA (Radiation Therapy Oncology Group-American Society of Therapeutic Radiology and Oncology (RTOG-ASTRO) Phoenix Consensus)
2. Conventional imaging: CT Abdomen/Pelvis (MRI if CT contraindicated) or MRI or bone scan. Conventional imaging not required for low-risk disease (T1-T2a, PSA < 10 ng/ml, and Gleason < 6/Group 1).
3. External beam radiation therapy +/- androgen deprivation therapy after prostatectomy OR radical prostatectomy, cryosurgery, high intensity focused ultrasound, or brachytherapy after external beam radiation therapy  
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
PET scanning for patients with prostate cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • FDG-PET/CT scanning
    • Diagnostic Workup and Diagnosis
    • Surveillance   
For members with contracts without primary coverage criteria, PET scanning for patients with Prostate Cancer is considered investigational and is not covered for any indication or any circumstance other than those listed above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to November 06, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Positron emission tomography (PET) scanning for patients with recurrent prostate cancer meets primary coverage criteria for effectiveness and is covered for:
18F Fluciclovine PET/CT or 11C Choline PET/CT
 
Management (of treatment or disease)
Indicated when ALL of the following criteria are met:
        • Original clinical stage T1-T3 and NX or N0 treated with prostatectomy and/or radiation therapy, with biochemically recurrent/persistent disease (1); and
        • Results of conventional imaging (2) performed within the past 60 days are negative for metastasis; and
        • Patient is a candidate for curative intent salvage therapy (3); and
        • PSA level is > 1 ng/ml; OR PSA is rising and prostate MRI cannot be performed or is nondiagnostic
        • PET/CT with 18F Fluciclovine or 11C Choline has not been performed within the past 3 months
68Ga Prostate-specific membrane antigen (PSMA) PET/CT or 18F-DCFPyL (piflufolastat or Pylarify) PET/CT
 
Management (of treatment or disease)
Indicated when ALL of the following criteria are met:
        • Original clinical stage T1-T3 and NX or N0 treated with prostatectomy and/or radiation therapy, with biochemically recurrent/persistent disease (1); and
        • Results of conventional imaging (2) performed within the past 60 days are negative for metastasis; and
        • Patient is a candidate for curative intent salvage therapy (3); and
        • PSA level is > 1 ng/ml or PSA is rising; and
        • PET/CT has not been performed within the past 3 months;  
Notes:
        1. Post-prostatectomy (PSA should be 0 after surgery):
Persistence: Detection of a PSA higher than 0 within the first three months after surgery; Recurrence: PSA initially undetectable, then rising PSA > 0.2 ng/ml, with a second confirmatory level ≥ 0.2 ng/mL (American Urological Association definition)
 
Post-radiation therapy:
Recurrence: rise by > 2 ng/mL above the nadir PSA (Radiation Therapy Oncology Group-American Society of Therapeutic Radiology and Oncology (RTOG-ASTRO) Phoenix Consensus)
2. Conventional imaging: CT Abdomen/Pelvis (MRI if CT contraindicated) or MRI or bone scan. Conventional imaging not required for low-risk disease (T1-T2a, PSA < 10 ng/ml, and Gleason < 6/Group 1).
3. External beam radiation therapy +/- androgen deprivation therapy after prostatectomy OR radical prostatectomy, cryosurgery, high intensity focused ultrasound, or brachytherapy after external beam radiation therapy
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria  
PET scanning for patients with prostate cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • FDG-PET/CT scanning
    • Diagnostic Workup and Diagnosis
    • Surveillance*   
For members with contracts without primary coverage criteria, PET scanning for patients with Prostate Cancer is considered investigational and is not covered for any indication or any circumstance other than those listed above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.  
 
Effective Prior to March 13, 2022
Positron emission tomography (PET) scanning meets primary coverage criteria for effectiveness and is covered for patients with recurrent prostate cancer for:
 
Subsequent treatment strategy for 11C Choline PET/CT or 18F Fluciclovine PET/CT when all of the following criteria are met:
    • Original clinical stage T1-T3 or NX or N0 s/p prostatectomy and/or radiation; AND
    • Biochemically recurrent/persistent disease; AND
    • Conventional imaging is negative or not indicated; AND
    • MRI pelvis is negative or non-diagnostic for local recurrence; and
    • Patient is a candidate for local salvage therapy; AND
    • PSA is >1ng/ml
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET scanning for patients who have or are suspected of having prostate cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following:
    • the differential diagnosis of carcinoma of the prostate.
    • any other indication not specifically listed as covered above.  
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
For members with contracts without primary coverage criteria, PET scanning for patients who have or are suspected of having prostate cancer is considered investigational for the following:
    • the differential diagnosis of carcinoma of the prostate.
    • any other indication not specifically listed as covered above.  
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective September 2018 to October 2019
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Positron emission tomography (PET) imaging using Choline C 11 meets member benefit certificate of primary coverage criteria for effectiveness and is covered for recurrent prostate cancer in adult males based on elevated blood PSA after therapy with non-informative conventional imaging.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET scanning for the differential diagnosis of carcinoma of the prostate, or for any other indication related to the diagnosis of carcinoma of the prostate, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, PET scanning for the differential diagnosis of carcinoma of the prostate, or for any other indication related to the diagnosis of carcinoma of the prostate, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
PET scanning with 18-FDG, 68 Gallium, F18 Fluciclivine or any other radiotracer not mentioned above for the diagnosis and treatment of prostate cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.  
 
For members with contracts without primary coverage criteria, 18-FDG, 68 Gallium, F18 Fluciclivine or any other radiotracer not mentioned above for the diagnosis and treatment of prostate is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to September 2018
Positron emission tomography (PET) imaging using Choline C 11 meets member certificate of benefit Primary Coverage Criteria for effectiveness and is covered for recurrent prostate cancer in adult males with non-informative conventional imaging.
 
PET scanning for the differential diagnosis of  carcinoma of the prostate, or for any other indication related to the diagnosis of carcinoma of the prostate, is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For contracts without primary coverage criteria, (PET) imaging using Choline C 11 is covered for recurrent prostate cancer in adult males with non-informative conventional imaging.
 
PET scanning with 18-FDG for prostate cancer does not meet benefit certificate primary  coverage criteria that the be scientific evidence of effectiveness.  This use of FDG PET is also the subject of an ongoing trial (NCT00282906).
 
For contracts without primary coverage criteria the use of 18-FDG PET for the diagnosis  of prostate cancer would be considered investigational.  
 
Rationale:
The FDA website provided the following information on studies to support the use of Choline C 11 for PET imaging to assist in the diagnosis of recurrent prostate cancer.  A systematic review of published reports identified four studies that contained data sufficient to compare11C-choline PET imaging to histopathology (truth standard) among patients with suspected prostate cancer recurrence and non-informative conventional imaging (for most patients, CT or MRI). In general, the suspected recurrence criteria consisted of at least two sequential PSA levels of > 0.2 ng/mL for men who had undergone prostatectomy and PSA levels of ≥ 2 ng/mL above the post-therapy nadir for men who had undergone radiotherapy. The studies were predominantly single clinical site experiences and image acquisition generally surveyed radioactivity distribution from the base of the pelvis to the base of the skull.
Prospective studies: Two studies examined the ability of 11C-choline PET/CT to detect prostate cancer in pelvic and/or retroperitoneal lymph nodes among patients who had previously undergone radical prostatectomy. Both studies used a truth standard of lymph node histopathology. 11C-choline images were interpreted by readers masked to clinical information; surgical resection of lymph nodes was performed by surgeons aware of the 11C-choline PET/CT results.
In the first study by Scattoni  and colleagues (2007), 25 patients who underwent 11C-choline PET/CT and conventional imaging (CT or MRI) were scheduled to undergo pelvic or pelvic plus retroperitoneal lymphadenectomy following the imaging identification of suspected lymph node metastases. The median PSA was 2.0 ng/mL (range 0.2 to 23. ng/mL). The study excluded subjects with metastatic disease detected by bone scintigraphy or isolated prostatic fossa recurrence. Among the 25 patients, 21 had positive 11C-choline PET/CT scans; histopathology verified cancer in 19 of these patients. Lymph node histopathology detected no cancer among the four patients who had surgery based only on positive conventional imaging; 11C-choline PET/CT was negative in all four patients. The study report included information for patients who had non-informative conventional imaging (CT or MRI, bone scintigraphy and transrectal ultrasound).  
In the second study by Rinnab  and colleagues (2008), 15 patients were scheduled to undergo pelvic or pelvis plus retroperitoneal lymphadenectomy solely based upon positive 11C-choline PET/CT imaging in the setting of negative conventional imaging (ultrasound and/or CT and/or MRI and/or bone scintigraphy). The median PSA was 2.0 ng/mL (range 1.0 to 8.0 ng/mL); all patients had previously undergone radical prostatectomy. Eight of the 15 patients had cancer verified by lymph node histology; histology detected no cancer in seven patients.
Retrospective Studies: Two studies were retrospective reviews of patients who underwent 11C-choline PET/CT and had histopathology obtained from biopsy of the prostatic fossa or other suspected recurrence sites.
In the third study by Reske et al (2008), 11C-choline PET/CT imaging was performed among 36 patients with suspected prostate cancer recurrence and 13 subjects without suspected recurrence (controls). Prostatic fossa biopsies were performed among the patients with suspected recurrence. All the patients and control subjects had previously undergone radical prostatectomy; patient with suspected recurrence had no evidence of cancer using conventional clinical evaluations, including trans-rectal ultrasound and bone scintigraphy. PET/CT scans were interpreted by readers masked to clinical information. Median PSA was 2.0 ng/mL (range 0.3 – 12.1 ng/mL) for patients with suspected recurrence and 0.1 ng/mL (range 0.0 – 0.2 ng/mL) in control subjects. Prostatic fossa biopsy showed cancer in 33 of the 36 patients with suspected recurrence. PET/CT scans were positive in 25 of the 36 patients; two patients had false positive scans (one scan in a control subject and one scan in a suspected recurrence subject who had no cancer detected on prostatic fossa biopsy). Among the 13 control subjects, 12 had negative PET/CT scans.
In the fourth study by Mithcell (2012), 34 patients with negative conventional imaging underwent 11C-choline PET/CT and subsequently had biopsies of suspected recurrence sites. The median PSA level of the 34 patients was 3.9 ng/mL (range 0.2 to 65.0 ng/mL); 22 of the patients had previously undergone radical prostatectomy and 12 had received other therapy (radiotherapy, anti-androgen therapy or cryotherapy). 11C-choline PET/CT images were positive in 30 patients and negative in four patients. Cancer was verified by histopathology in 29 patients; 25 had positive PET/CT images and four had negative PET/CT images. Five patients with positive PET/CT images did not have cancer confirmed with histopathology.  
 
Within each study at least half the patients with non-informative conventional imaging had positive 11C-choline PET/CT images and histologically verified recurrent prostate cancer.  In the 3rd and 4th studies, PSA levels were generally lower for patients with negative 11 C-choline PET/CT results than for patients with positive results.  In the 3rd study , the median PSA was 2.6 ng/mL (range 0.6 – 12.1 ng/mL) among the 23 patients with true positive images; nine out of 11 patients with false negative or false positive images had PSA levels < 2 ng/mL. In the 4th study, the median PSA was 4.2 ng/mL (range 0.2 – 65.0 ng/mL) among the 25 patients with true positive images; PSA levels < 2 ng/mL were observed in four of the nine patients with false negative or false positive images. These data, combined with other published reports, suggest that 11C-choline PET imaging performance may be more reliable among patients with blood PSA levels > 2 ng/mL, compared to patients with lower levels.
 
Ongoing Clinical Trials:
  • NCT00804245 – “A Pilot Study of Use of 11C-Choline PET-CT in the Metastatic Evaluation of Patients With Newly Diagnosed High Risk Adenocarcinoma of the Prostate”; estimated enrollment 78 and a completion date of 12/2015.
 
  • NCT00282906 [F-18]-Fluorodeoxglucose (FDG)Positron Emission Tomography and Comptued Tomography (PET-CT) in metastatic prostate cancer.  It is an ongoing, single center, NIH funded, trial.
 
2013 Update
A search of the MEDLINE database through August 2013 did not reveal any new literature that would prompt a change in the coverage statement.  
 
2014 Update
A literature search conducted through September 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In a meta-analysis of 10 studies (n=637) by Umbehr et al on initial prostate cancer evaluation, pooled sensitivity was 84% (95% CI, 68% to 93%) and specificity was 79% (95% CI, 53% to 93%) (Umbehr, 2013).  In the analysis of 12 studies (n=1055) on patients with biochemical failure after local treatment, the pooled sensitivity was 85% (95% CI, 79% to 89%) and specificity was 88% (95% CI, 73% to 95%).
 
In a meta-analysis by von Eyben and Kairemo, the pooled sensitivity and specificity of choline PET-CT for detecting prostate cancer recurrence in 609 patients was 0.62 (95% CI, 0.51 to 0.66) and 0.92 (95% CI, 0.89 to 0.94), respectively (von Eyben, 2014). In an evaluation of 280 patients from head-to-head studies comparing choline PET-CT with bone scans, PET-CT identified metastasis significantly more often than bone scanning (127 [45%] vs 46 [16%], respectively; odds ratio, 2.8; 95% CI, 1.9 to 4.1; p<0.001). The authors also reported results of the choline PET-CT changed treatment in 381 (41%) of 938 patients. Complete prostate-specific antigen (PSA) response occurred in 101 of 404 (25%) patients.
 
Mohsen et al conducted a meta-analysis on 23 studies on C11-acetate PET imaging for primary or recurrent prostate cancer (NCCN, 2014). Pooled sensitivity for primary tumor evaluation was 75.1% (69.8% to 79.8%) and specificity was 75.8% (72.4% to 78.9%).For detection of recurrence, sensitivity was 64% (59% to 69%) and specificity was 93% (83% to 98%). While study quality was considered poor, low sensitivities and specificities appear to limit the utility of C11-acetate imaging.
 
NCCN guidelines on prostate cancer indicate C11 choline PET may be considered for biochemical failure after primary treatment, ie, radiation therapy or radical prostatectomy. (70) NCCN considers PET investigational for initial diagnosis and staging and notes FDG or fluoride PET should not be used in the community setting outside of a registry. Additionally, the routine use of PET-CT is not recommended due to limited evidence on its utility.
 
The European Association of Urology guidelines on prostate cancer indicate C11 choline PET-CT has limited value unless PSA levels are greater than 1.0 ng/mL (Heidenreich, 2014).
 
2015 Update
A literature search conducted through September 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Current NCCN guidelines for prostate cancer indicate that C-11-choline PET may be considered for biochemical failure after primary treatment, ie, radiotherapy or radical prostatectomy, although further study is needed to determine the best use of this imaging modality in men with prostate cancer (NCCN, 2015). FDG or fluoride PET should not be used in the community setting outside of a registry. Additionally, routine use of PET/CT is not recommended routinely, for initial assessment or in other settings, due to limited evidence of clinical utility.
 
The European Association of Urology guidelines for prostate cancer indicate that C-11-choline PET/CT has limited value unless PSA levels exceed 1.0 ng/mL (Heidenreich, 2014).  In meta-analysis of 14 studies (total N=1667) of radiolabelled choline PET/CT for restaging prostate cancer, Treglia et al (2014) reported a maximum pooled sensitivity of 0.77 (95% CI, 0.71 to 0.82) in patients with PSA rate of increase greater than 2 ng/mL per year (Treglia, 2014). Pooled sensitivity was lower for patients with PSA rate of increase less than 2 ng/mL per year or with PSA doubling time of 6 months or less. In meta-analysis of 11 studies (total N=609) of radiolabelled choline PET/CT for staging or restaging prostate cancer, Von Eyben et al (2014) reported pooled sensitivity and specificity of 0.59 (95% CI, 0.51 to 0.66) and 0.92 (95% CI, 0.89 to 0.94), respectively (von Eyben, 2014). Pooled positive predictive value and NPV were 0.70 and 0.85, respectively.
 
2017 Update
 
In 2016, Liu et al and Ouyang et al conducted meta-analyses comparing the diagnostic accuracy of 4 radiotracers (fluorine-18 fluorodeoxyglucose, carbon-11 choline [11C-choline], fluorine 18 fluorocholine [18F-FCH], and carbon-11 acetate) in detecting prostate cancer (Liu, 2016; Ouyang, 2016). The literature search by Liu et al, conducted through July 2015, identified 56 studies (total N=3586 patients) for inclusion. Using the QUADAS-2 system to evaluate study quality, the authors determined that the studies were reliable, with scores of 6 to 9 out of 10.  The search by Ouyang et al included studies using elastography and was conducted through April 2015. Study quality was not addressed.
 
Prostate Cancer Restaging
A 2016 meta-analysis by Fanti et al assessed 11C-choline PET/CT accuracy in restaging of prostate cancer patients with biochemical recurrence after initial treatment with curative intent (Fanti, 2016).   The literature search, conducted through December 2014, identified 12 studies (total N=1270 patients) for inclusion in the analysis. Pooled sensitivity and specificity was 89% (95% CI, 83% to 93%) and 89% (95% CI, 73% to 96%).
 
Prostate Cancer Management
In 2017, Akin-Akintayo et al evaluated the role of FACBC (anti–1-amino-3-[18F] fluorocyclobutane-1-carboxylic acid or fluciclovine) PET/CT in the management of post-prostatectomy patients with PSA failure being considered for salvage radiotherapy (Akin-Akintayo, 2017).  Forty-two patients who were initially planning radiotherapy due to post-prostatectomy PSA failure underwent fluciclovine PET/CT. Based on the PET/CT results, 17 (40.5%) patients changed a decision relating to the radiotherapy: 2 patients received hormonal therapy rather than radiotherapy when fluciclovine showed extrapelvic disease; 11 patients increased the radiotherapy field from prostate bed only to prostate plus pelvis; and 4 patients reduced the radiotherapy fields from prostate plus pelvis to prostate bed only.
 
Current NCCN guidelines for prostate cancer indicate that 11C-choline PET may be considered for biochemical failure after primary treatment (ie, radiotherapy or radical prostatectomy), although further study is needed to determine the best use of this imaging modality in patients with prostate cancer (NCCN, V2.2017).   FDG or fluoride PET should not be used routinely for initial assessment or in other settings, due to limited evidence of clinical utility.
 
Evidence for the use of 11C-choline PET and -PET/CT for diagnosis, staging, and restaging of prostate cancer, consists of meta-analyses. The choice of radiotracer affects the sensitivity and specificity of the scans, with most evidence showing that the use of 11C-choline results in the highest sensitivities and specificities. Further study is needed to compare PET and PET/CT with other imaging techniques, such as MRI and radionuclide bone scan. One prospective study has looked at the use of FACBC PET/CT in the management of post-prostatectomy patients with PSA failure considering salvage radiotherapy. PET/CT results altered the radiotherapy treatment plans in 40% of the patients. The evidence supports the use of 11C-choline PET and PET/CT for the diagnosis, staging and restaging, and surveillance of prostate cancer.
 
Prostate Cancer and 68GA-PET and 68GA-PET/CT
A 2016 systematic review by Perera calculated the sensitivity, specificity, and predictive value of 68Gaprostate-specific membrane antigen (PSMA) PET in advanced prostate cancer (Perera, 2016).   The literature search, conducted through April 2016, identified 16 studies (total N=1309 patients) for inclusion, though only 11 studies reported histopathologic correlations. Four studies allowed for calculating the predictive ability of 68Ga-PSMA PET; they showed a pooled sensitivity of 86% (95% CI, 37% to 98%) and a pooled specificity of 86% (95% CI, 3% to 100%). The other studies were used to assess 68Ga-PSMA PET positivity by the amount of radiopharmaceutical injected and for detection of primary and metastatic lesions. Reviewers noted that these analyses were exploratory, because most studies were small, retrospective, from single institutions, and had heterogeneous patient cohorts.
 
Evidence for the use of 68Ga in PET consists of a systematic review of small single-institution studies. The confidence intervals of the sensitivity and specificity are wide, indicating uncertainty in the results provided. The evidence does not support the use of 68Ga-PET and -PET/CT for the diagnosis, staging and restaging, and surveillance of prostate cancer.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2018. No new literature was identified that would prompt a change in the coverage statement.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through July 9, 2018. The key identified literature is summarized below.
 
Prostate Cancer Staging and Restaging
Other systematic reviews, including those by Sandgren et al and Albisinni et al, have also reported that 11C-choline PET/CT exhibits high sensitivity and specificity estimates in the staging and restaging of prostate cancer (Sandgren, 2017; Albisinni 2018).
 
Bach-Gansmo et al conducted a retrospective study assessing the use of anti–1-amino-3-[18F] fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) in the staging of biochemically recurrent prostate cancer (Bach-Gansmo, 2017). The reference standard was histologic confirmation, which was blinded to PET findings. Detection rates were calculated for the prostate, extra-prostate, and whole body at quartiles of PSA levels. At the highest quartile (>6.0 ng/mL), detection rates were 69%, 69%, and 86% for the prostate, extra-prostate, and whole body scans, respectively. For PSA levels from 2.0 to 6.0 ng/mL, detection rates were 50% 46%, and 75%, respectively. For PSA levels from 0.8 to 2.0 ng/mL, detection rates were 22%, 45%, and 59%, respectively. For the lowest quartile (≤0.8 ng/mL), detection rates were 14%, 31%, and 41%, respectively. (Note that BCBSA extrapolated detection rates from a graphic.)
 
Prostate Cancer Management
Andriole et al presented results from the LOCATE trial (Andriole, 2018). The study population consisted of 213 men who had undergone curative intent treatment of histologically confirmed prostate cancer and were suspected to have recurrence based on rising PSA levels. Fluciclovine-avid lesions were detected in 122 (57%) patients. Compared with management plans specified by the treating physicians prior to the PET scans, 126 (59%) patients had a change in management. The most frequent change in management was from salvage or noncurative systemic therapy to watchful waiting (n=32) and from noncurative systemic therapy to salvage therapy (n=30).
 
Akin-Akintayo et al evaluated the role of fluciclovine PET/CT in the management of post-prostatectomy patients with PSA failure being considered for salvage radiotherapy (Akin-Akintayo, 2017).  Forty-two patients who were initially planning radiotherapy due to post-prostatectomy PSA failure underwent fluciclovine PET/CT. Based on the PET/CT results, 17 (40.5%) patients changed a decision relating to the radiotherapy: 2 patients received hormonal therapy rather than radiotherapy when fluciclovine showed extrapelvic disease; 11 patients increased the radiotherapy field from prostate bed only to prostate plus pelvis, and 4 patients reduced the radiotherapy fields from prostate plus pelvis to prostate bed only.
 
68Ga-PET and 68Ga-PET/CT
The Albisinni et al (2018) review, discussed in the 11C-choline PET/CT section, and a systematic review by Eissa et al (2018)" noted that an advantage of using 68Ga prostate-specific membrane antigen (PSMA) PET compared with other radiotracers is the potential to detect local and distant recurrences in patients with lower PSA levels (<0.5 ng/ml).
 
The current NCCN guidelines for prostate cancer (v.3.2018) note that 68Ga-PSMA PET “may provide better detection of recurrences at lower PSA levels than reported for FDA-approved imaging agents.”\l " (NCCN: Prostate Ca, V3.2018).  However, NCCN guidelines consider 68Ga-PSMA investigational at this time.
 
Evidence for the use of 68Ga-PET and 68Ga-PET/CT consists of a systematic review of small single-
Institution studies.  The confidence intervals of the sensitivity and specificity are wide, indicating uncertainty in the results.  The evidence does not support the use of 68Ga-PET and 68Ga-PET/CT for the diagnosis, staging, restaging, and surveillance of prostate cancer.
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2019. No new literature was identified that would prompt a change in the coverage statement.
 
2020 Update
A literature search was conducted through January 2020.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2021. No new literature was identified that would prompt a change in the coverage statement.
 
November 2021 Update
A literature review was performed through September 2021. Following is a summary of the key literature to date.
 
DIAGNOSTIC WORKUP
Prostate cancer is staged using the American Joint Committee on CancerTNM system. Advanced imaging is not indicated for very low and low-risk groups. Multiparametric MRI (mpMRI, referring to prostate MRI protocol within this guideline) can be used in the staging and characterization of prostate cancer. CT is generally not sufficient to evaluate the prostate gland but can be used for initial evaluation of nodal and/or visceral metastatic disease.
 
The prospective multicenter, randomized Phase III PRECISION (PRostate Evaluation for Clinically Important Disease: Sampling Using Image-guidance Or Not?)trial compared mpMRI-targeted biopsy to standard transrectal ultrasoundguided biopsy in 500 men with clinical suspicion of prostate cancer (elevated PSA, abnormal digital rectal exam, or both) who had not undergone biopsy previously. The mpMRI-targeted evaluation was able to detect prostate cancer in 38% of men compared with 26% in the standard biopsy group (P = 0.005). Fewer men in the mpMRI group were diagnosed with clinically insignificant cancers (defined as Gleason 6). (1)
 
In a meta-analysis of 75 studies comparing CT to MRI for initial staging, the pooled data for extracapsular extension and T3 detection showed sensitivity and specificity of 57% and 91% for CT vs 61% and 88% for MRI. (2) For detection of lymph node metastases, the differences in performance of CT and MRI were not statistically significant. (3) Findings from another prospective study confirmed the equivalency of CT and MRI for lymph node staging. (4) For intermediate risk or above, abdominal imaging with contrast should be performed if the risk of pelvic lymph node metastases is greater than 10%. FDG-PET is not indicated, as physiologic activity in the bladder obscures tumor detection. (5) Additionally, there is limited evidence to support 11C-choline and 18F fluciclovine PET for initial staging of prostate cancer
 
MANAGEMENT
For active surveillance, the NCCN recommends mpMRI be considered for suspected anterior and/or aggressive cancers when PSA increases and prostate biopsies are negative. (6) Studies of 11C-choline, 18F-fluciclovine, and prostate-specific membrane antigen (PSMA) PET support their accuracy in evaluating biochemical recurrence (BCR). (7-9)
 
The recent FALCON (18F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer) trial found the detection ability of 18F-fluciclovine PET after radical treatment (prostatectomy or radiation therapy/brachytherapy) broadly proportional to PSA level (one-third scans positive when PSA ≤ 1 ng/mL, compared to 93% positive with PSA greater than 2 ng/mL). (10) Results were similar to that of the previous (LOCATE) study (patient-level detection of 56% with overall 63% management changes, compared with 57% and 59%, respectively), the latter limited to patients with negative or equivocal conventional imaging before 18F-fluciclovine PET/CT. Where 18F-fluciclovine guided salvage therapy, the PSA response rate was higher than when 18F-fluciclovine was not involved (15 out of 17 [88%] vs 28 out of 39 [72%]). (10) 68-Ga PSMA PET was found to have higher diagnostic accuracy than other radiotracers for biochemical recurrence (overall detection rate of 74%) by one systematic review, especially at low PSA values, resulting in management change in 53% of patients. (9) A systematic review and network meta-analysis of 12 studies encompassing eight radiotracers found comparable performance of 68Ga-PSMA-11 and 18F-DCFPyL. (11) Another systematic review, this including 43 studies and 5832 patients, found no difference in detection rate between PSMA tracers based on PSA level, doubling time, or velocity. (9)
 
Although there are some studies showing a correlation between MRI stability and Gleason stability, the American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology 2017 Guidelines for Clinically Localized Prostate Cancer do not currently recommend serial MRI for surveillance. (12-15)
 
Current References
    1. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;378(19):1767-77. PMID: 29552975
    2. de Rooij M, Hamoen EH, Witjes JA, et al. Accuracy of magnetic resonance imaging for local staging of prostate cancer: a diagnostic meta-analysis. Eur Urol. 2016;70(2):233-45. PMID: 26215604
    3. Hovels AM, Heesakkers RA, Adang EM, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol. 2008;63(4):387-95. PMID: 18325358
    4. Heck MM, Souvatzoglou M, Retz M, et al. Prospective comparison of computed tomography, diffusion-weighted magnetic resonance imaging and [11C]choline positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2014;41(4):694-701.
    5. PMID: 24297503
5. Jadvar H. PET of glucose metabolism and cellular proliferation in prostate cancer. J Nucl Med. 2016;57(Suppl 3):25S-9S. PMID: 27694167
6. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer (Version 2.2021). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.
7. Ren J, Yuan L, Wen G, et al. The value of anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT in the diagnosis of recurrent prostate carcinoma: a meta-analysis. Acta Radiol. 2016;57(4):487-93. PMID: 25907118
8. Yu CY, Desai B, Ji L, et al. Comparative performance of PET tracers in biochemical recurrence of prostate cancer: a critical analysis of literature. Am J Nucl Med Mol Imaging. 2014;4(6):580-601. PMID: 25250207
9. Crocerossa F, Marchioni M, Novara G, et al. Detection rate of prostate specific membrane antigen tracers for positron emission tomography/computerized tomography in prostate cancer biochemical recurrence: a systematic review and network meta-analysis. J Urol. 2020;205(2):356-69. PMID: 32935652
10. Scarsbrook AF, Bottomley D, Teoh EJ, et al. Effect of 18F-fluciclovine positron emission tomography on the management of patients with recurrence of prostate cancer: results from the FALCON trial. Int J Radiat Oncol Biol Phys. 2020;107(2):316-24. PMID: 32068113
11. Alberts IL, Seide SE, Mingels C, et al. Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis. Eur J Nucl Med Mol Imaging. 2021;48(9):2978-89. PMID: 33550425
12. Felker ER, Wu J, Natarajan S, et al. Serial magnetic resonance imaging in active surveillance of prostate cancer: incremental value. J Urol. 2016;195(5):1421-7. PMID: 26674305
13. Lai WS, Gordetsky JB, Thomas JV, et al. Factors predicting prostate cancer upgrading on magnetic resonance imaging-targeted biopsy in an active surveillance population. Cancer. 2017;123(11):1941-8. PMID: 28140460
14. Rais-Bahrami S, Turkbey B, Rastinehad AR, et al. Natural history of small index lesions suspicious for prostate cancer on multiparametric MRI: recommendations for interval imaging follow-up. Diagn Interv Radiol. 2014;20(4):293-8. PMID: 24808435
15. Sanda MG, Cadeddu JA, Kirkby E, et al. Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part I: risk stratification, shared decision making, and care options. J Uro l. 2018;199(3):683-90. PMID: 29203269
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2022. No new literature was identified that would prompt a change in the coverage statement.
 
PSMA imaging is needed for patient selection prior to treatment of metastatic castration-resistant prostate cancer (mCRPC) with the radioligand therapeutic agent lutetium Lu 177 vipivotide tetraxetan. In the randomized, multi-center trial demonstrating prolonged imaging-based progression-free survival and overall survival of this treatment, all patients were required to have received at least one AR pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. (12)
 
 
New References
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer (Version 4.2022). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2022.
 
Sartor O, deBono J. Chi KN et al.  Lutetuim-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;1(12)1091-103. PMID 34161051
  
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2023. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2024.
 
Evidence finds PSMA-PET to be more accurate than CT and bone scan in assessing pelvic nodal and distant metastases, though not sensitive enough to forego pelvic lymph node dissection in those with high-risk disease.(Hofman et al, 2020; Stabile et al, 2022).  Confirmation of equivocal findings or nondiagnostic findings may be aided by PSMA-PET given its high specificity. However, data on patient centered outcomes remains limited, with several guidelines advising caution when making therapeutic decisions based on metastases identified by PSMA-PET alone (Eastham et al, 2022; Mottet et al, 2023).
 
Evidence finds PSMA-PET to be more accurate than CT and bone scan in assessing pelvic nodal and distant metastases, though not sensitive enough to forego pelvic lymph node dissection in those with high-risk disease.(Hofman et al, 2020; Stabile et al, 2022).  Confirmation of equivocal findings or nondiagnostic findings may be aided by PSMA-PET given its high specificity. However, data on patient centered outcomes remains limited, with several guidelines advising caution when making therapeutic decisions based on metastases identified by PSMA-PET alone (Eastham et al, 2022; Mottet et al, 2023).
 
Although there are some studies showing a correlation between MRI stability and Gleason stability, the American Urological Association/American Society for Radiation Oncology2022Guidelines for Clinically Localized Prostate Cancer endorsed by Society of Urologic Oncology do not currently recommend serial MRI for surveillance (Eastham et al, 2022; Felker et al, 2016; Lai et al, 2017; Rais-Bahrami et al, 2014).
CPT/HCPCS:
78811Positron emission tomography (PET) imaging; limited area (eg, chest, head/neck)
78812Positron emission tomography (PET) imaging; skull base to mid thigh
78813Positron emission tomography (PET) imaging; whole body
78814Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; limited area (eg, chest, head/neck)
78815Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; skull base to mid thigh
78816Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; whole body
A9515Choline c 11, diagnostic, per study dose up to 20 millicuries
A9587Gallium ga 68, dotatate, diagnostic, 0.1 millicurie
A9588Fluciclovine f 18, diagnostic, 1 millicurie
A9593Gallium ga-68 psma-11, diagnostic, (ucsf), 1 millicurie
A9594Gallium ga-68 psma-11, diagnostic, (ucla), 1 millicurie
A9595Piflufolastat f-18, diagnostic, 1 millicurie
A9596Gallium ga-68 gozetotide, diagnostic, (illuccix), 1 millicurie
A9608Flotufolastat f 18, diagnostic, 1 millicurie
A9800Gallium ga-68 gozetotide, diagnostic, (locametz), 1 millicurie
References: Akin-Akintayo OO, Jani AB, Odewole O, et al.(2017) Change in salvage radiotherapy management based on guidance with FACBC (Fluciclovine) PET/CT in postprostatectomy recurrent prostate cancer. Clin Nucl Med. Jan 2017;42(1):e22-e28. PMID 27749412

Akin-Akintayo OO, Jani AB, Odewole O, et al.(2017) Change in salvage radiotherapy management based on guidance with FACBC (Fluciclovine) PET/CT in postprostatectomy recurrent prostate cancer. Clin Nucl Med. Jan 2017;42(1):e22-e28. PMID 27749412.

Albisinni S, Aoun F, Marcelis Q, et al.(2018) Innovations in imaging modalities for recurrent and metastatic prostate cancer: a systematic review. Minerva Urol Nefrol. Aug 2018;70(4):347-360. PMID 29388415

Andriole GL, Kostakoglu L, Chau A, et al.(2018) The Impact of Positron Emission Tomography with (18)F-Fluciclovine on the Management of Patients with Biochemical Recurrence of Prostate Cancer: Results from the LOCATE Trial. J Urol. Sep 1 2018. PMID 30179618

Bach-Gansmo T, Nanni C, Nieh PT, et al.(2017) Multisite Experience of the Safety, Detection Rate and Diagnostic Performance of Fluciclovine ((18)F) Positron Emission Tomography/Computerized Tomography Imaging in the Staging of Biochemically Recurrent Prostate Cancer. J Urol. Mar 2017;197(3 Pt 1):676-683. PMID 27746282

Fanti S, Minozzi S, Castellucci P, et al.(2016) PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data. Eur J Nucl Med Mol Imaging. Jan 2016;43(1):55-69. PMID 26450693.

Heidenreich A, Bastian PJ, Bellmunt J et al.(2014) EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced, Relapsing, and Castration-Resistant Prostate Cancer. Eur Urol 2014; 65(2):467-79.

Liu J, Chen Z, Wang T, et al.(2016) Influence of four radiotracers in PET/CT on diagnostic accuracy for prostate cancer: a bivariate random-effects meta-analysis. Cell Physiol Biochem. 2016;39(2):467-480. PMID 27383216

Mitchell C, Kwon E, Lowe V, et al.(2012) Detection of consolidated disease recurrences of prostate cancer by 11C-choline PET/Scan: results confirmed by surgical resection; supplemented with subject-level data. J Urol. 2012; 187:e823.

Mitchell C, Kwon E, Lowe V, et al.(2012) Impact of 11C-choline PET/CT scan on detection of recurrent prostate cancer in men with biochemical recurrence following failed initial treatment; supplemented with subject-level data. J Urol. 2012; 187:e823.

Mohsen B, Giorgio T, Rasoul ZS et al.(2013) Application of (11) C-acetate positron-emission tomography (PET) imaging in prostate cancer: systematic review and meta-analysis of the literature. BJU Int 2013; 112(8):1062-72.

National Comprehensive Cancer Network(2022) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer (Version 4.2022). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2022.

National Comprehensive Cancer Network.(2014) Clinical Practice Guidelines in Oncology. Prostate Cancer V1.2014. Available online at: http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Last accessed January, 2014.

National Comprehensive Cancer Network.(2015) Clinical Practice Guidelines in Oncology. Prostate Cancer V1.2015. http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Accessed December 11, 2014.

NCT00282906.(2012) [F-18]-Fluorodeoxglucose (FDG)Positron Emission Tomography and Comptued Tomography (PET-CT) in metastatic prostate cancer. www.clinicaltrials.gov. Last accessed 10/30/2012.

NCT00804245.(2012) A Pilot Study of Use of 11C-Choline PET-CT in the Metastatic Evaluation of Patients With Newly Diagnosed High Risk Adenocarcinoma of the Prostate. www.clinicaltrials.gov. Last accessed 10/30/2012.

Ouyang Q, Duan Z, Lei J, et al.(2016) Comparison of meta-analyses among elastosonography (ES) and positron emission tomography/computed tomography (PET/CT) imaging techniques in the application of prostate cancer diagnosis. Tumour Biol. Mar 2016;37(3):2999-3007. PMID 26415734.

Perera M, Papa N, Christidis D, et al.(2016) Sensitivity, specificity, and predictors of positive 68Ga-Prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and metaanalysis. Eur Urol. Dec 2016;70(6):926-937. PMID 27363387.

Reske SN, Blumstein NM, Glatting G.(2008) [11C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy. Eur J Med Mol Imaging. 2008; 35:9-17.

Rinnab L, Mottaghy FM, Simon J, et al.(2008) [11C]choline PET/CT for targeted salvage lymph. Node dissection in patients with biochemical recurrence after primary curative therapy for prostate cancer. Urologia Int. 2008; 81:191-7.

Sandgren K, Westerlinck P, Jonsson JH, et al.(2017) Imaging for the detection of locoregional recurrences in biochemical progression after radical prostatectomy-a systematic review. Eur Urol Focus. Nov 10 2017. PMID 29133278

Scattoni V, Picchio M, Suardi N, et al.(2007) Detection of lymph-node metastases with integrated [11C]choline PET/CT in patients with PSA failure after radical retropubic prostatectomy: results confirmed by open pelvicretroperitoneal lymphadenectomy. Eur Urol. 2007; 52:423-9.

Treglia G, Ceriani L, Sadeghi R, et al.(2014) Relationship between prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in restaging prostate cancer patients: a metaanalysis. Clin Chem Lab Med. May 2014;52(5):725-733. PMID 24310773

von Eyben FE, Kairemo K.(2014) von Eyben FE, Kairemo K. Meta-analysis of 11C-choline and 18F-choline PET/CT for management of patients with prostate cancer. Nucl Med Commun 2014; 35(3):221-30.
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