Prostate Cancer Guidelines

Updated: Sep 23, 2020
  • Author: Chad R Tracy, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Guidelines

Guidelines Summary

Guidelines Contributor: Bagi RP Jana, MD Associate Professor of Medicine (Genitourinary Oncology), Division of Hematology and Oncology, University of Texas Medical Branch

Prostate Cancer Screening

Guidelines on prostate cancer screening have been issued by the following organizations:

  • American Cancer Society (ACS)
  • National Comprehensive Cancer Network (NCCN)
  • American Urological Association (AUA)
  • U.S. Preventive Services Task Force (USPSTF)
  • American College of Physicians (ACP)
  • European Society for Medical Oncology (ESMO)
  • European Association of Urology/European Society for Radiotherapy and Oncology/International Society of Geriatric Oncology (EAU/ESTRO/SIOG)

The guidelines differ in their recommendations regarding whether or not to provide routine prostate-specific antigen (PSA)–based prostate cancer screening, in what age groups and life expectancies, and at what intervals. The guidelines agree that PSA-based prostate cancer screening requires an informed, shared decision-making process, and that the decision should reflect the patient’s understanding of the possible benefits and risks and should respect the patient’s preferences and values. [201, 63, 202, 203, 204, 205, 58]

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Genetic Testing

National Comprehensive Cancer Network (NCCN) guidelines [41] recommend that at the time of initial diagnosis of prostate cancer, clinicians should inquire about family and personal history of cancer. The NCCN recommends germline genetic testing, with or without pretest genetic counseling, for patients with prostate cancer and any of the following:

  • A positive family history of cancer (eg, prostate, breast)
  • High-risk, very-high-risk, regional or metastatic prostate cancer, regardless of family history
  • Ashkenazi Jewish ancestry
  • Intraductal histology

Germline testing, when performed, should include the following:

  • MLH1, MSH2, MSH6, and  PMS2 (for Lynch syndrome)
  • The homologous recombination genes  BRCA2, BRCA1, ATM, PALB2,and  CHEK2

Clinicians may also consider a next-generation sequencing (NGS) panel to test for cancer predisposition. At minimum, the panel should include the following:

  • BRCA2
  • BRCA1
  • ATM
  • CHEK2
  • PALB2
  • MLH1
  • MSH2
  • MSH6
  • PMS2

​ Testing of additional genes may be appropriate, depending on the clinical context. For example, HOXB13 is a prostate cancer risk gene; although its presence does not currently have clear therapeutic implications in the advanced disease setting, testing for it may be valuable for family counseling.

Somatic tumor testing based on risk groups

NCCN recommendations for testing of prostate cancer tumors are as follows:

  • Tumor testing for homologous recombination gene mutations (HRRm) and for microsatellite instability (MSI) or mismatch repair deficiency (dMMR) can be considered in patients with regional prostate cancer.

  • Tumor testing for somatic HRRm (eg, BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51DCHEK2) is recommended in patients with metastatic prostate cancer.

  • Multigene molecular testing can be considered for patients with low- and favorable-intermediate risk prostate cancer and life expectancy ≥10 years.

  • The Decipher molecular assay can be considered as part of counseling for risk stratification in patients with PSA resistance/recurrence after radical prostatectomy.

  • If mutations in BRCA2, BRCA1, ATM, CHEK2,  or PALB2  are found, the patient should be referred for genetic counseling to assess for the possibility of hereditary breast and ovarian cancer (HBOC) syndrome.

  • If MSI testing is performed, testing using an NGS assay validated for prostate cancer is preferred. If high MSI (MSI-H) or dMMR is found, the patient should be referred for genetic counseling to assess for the possibility of Lynch syndrome. MSI-H or dMMR indicate eligibility for pembrolizumab in second and subsequent lines of treatment of castration-resistant prostate cancer.

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Multiparametric Magnetic Resonance Imaging

The National Comprehensive Cancer Network (NCCN) advises that although standard MRI techniques can be considered for initial evaluation of high-risk patients, multiparametric magnetic resonance imaging (mpMRI) can be used in the staging and characterization of prostate cancer. mpMRI images are defined as those acquired with at least one more sequence in addition to the anatomic T2-weighted images, such as diffusion-weighted imaging and dynamic contrast images. In addition, the NCCN guidelines recommend considering mpMRI in patients undergoing active surveillance if anterior and/or aggressive cancer is suspected when PSA increases and systematic prostate biopsies are negative. [41]

The 2016 EAU/ESTR/SIOG guidelines recommend mpMRI prior to performing a repeat biopsy when clinical suspicion of prostate cancer persists in spite of negative biopsies. During repeat biopsy, target any mpMRI lesions seen. Additionally, the guidelines recommend performing mpMRI for local staging and metastatic screening in predominantly Gleason pattern 4 intermediate risk patients and for local staging in high-risk localised prostate cancer. [205]

 

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Management of Clinically Localized Prostate Cancer

American Urological Association

Guidelines from the American Urological Association, the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO) for management of clinically localized prostate cancer include the following recommendations for very-low-risk and low-risk disease [88] :

  • Abdominal-pelvic CT or routine bone scans should not be performed as part of the staging of asymptomatic patients with very-low-risk or low-risk prostate cancer. (Strong Recommendation; Evidence Level: Grade C)
  • Clinicians should recommend active surveillance as the best available care option for patients with very-low-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
  • Clinicians should recommend active surveillance as the preferable care option for most patients with low-risk localized prostate cancer. (Moderate Recommendation; Evidence Level: Grade B)
  • Clinicians may offer definitive treatment (ie, radical prostatectomy or radiotherapy) to select low-risk localized prostate cancer patients who may have a high probability of progression on active surveillance. (Conditional Recommendation; Evidence Level: Grade B)
  • Clinicians should not add androgen deprivation therapy (ADT) to radiotherapy for low-risk localized prostate cancer, except to reduce the size of the prostate for brachytherapy. (Strong Recommendation; Evidence Level: Grade B)
  • Clinicians should inform low-risk prostate cancer patients considering whole gland cryosurgery that consequent side effects are considerable and survival benefit has not been shown in comparison with active surveillance. (Conditional Recommendation; Evidence Level: Grade C)
  • Clinicians should inform low-risk prostate cancer patients who are considering focal therapy or high-intensity focused ultrasound (HIFU) that these interventions are not standard care options because comparative outcome evidence is lacking. (Expert Opinion)
  • Clinicians should recommend observation or watchful waiting for men with a life expectancy ≤5 years with low-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade B)
  • In most cases of low-risk localized prostate cancer, tissue-based genomic biomarkers have not shown a clear role in the selection of candidates for active surveillance. (Expert Opinion)

For patients with intermediate-risk disease, care recommendations are as follows:

  • Clinicians should consider staging unfavorable intermediate-risk localized prostate cancer with cross-sectional imaging (CT or MRI) and bone scan. (Expert Opinion)
  • Clinicians should recommend radical prostatectomy or radiotherapy plus ADT as standard treatment options for patients with intermediate-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
  • Clinicians should inform patients that favorable intermediate-risk prostate cancer can be treated with radiation alone, but that the evidence basis is less robust than for combining radiotherapy with ADT. (Moderate Recommendation; Evidence Level: Grade B)
  • In select patients with intermediate-risk localized prostate cancer, clinicians may consider other treatment options such as cryosurgery. (Conditional Recommendation; Evidence Level: Grade C)
  • Active surveillance may be offered to select patients with favorable intermediate-risk localized prostate cancer; however, patients should be informed that this comes with a higher risk of developing metastases compared with definitive treatment. (Conditional Recommendation; Evidence Level: Grade C)
  • Clinicians should recommend observation or watchful waiting for men with a life expectancy ≤5 years with intermediate-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
  • Clinicians should inform patients with intermediate-risk prostate cancer who are considering focal therapy or HIFU that these interventions are not standard care options because comparative outcome evidence is lacking. (Expert Opinion)

For high-risk patients the guideline recommendations include the following:

  • Clinicians should stage high-risk localized prostate cancer patients with cross-sectional imaging (CT or MRI) and bone scan. (Clinical Principle)
  • Clinicians should recommend radical prostatectomy or radiotherapy plus ADT as standard treatment options for patients with high-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
  • Clinicians should not recommend active surveillance for patients with high-risk localized prostate cancer. Watchful waiting should be considered only in asymptomatic men with limited life expectancy (≤5 years). (Moderate Recommendation; Evidence Level: Grade C)
  • Cryosurgery, focal therapy, and HIFU treatments are not recommended for men with high-risk localized prostate cancer outside of a clinical trial. (Expert Opinion)
  • Clinicians should not recommend primary ADT for patients with high-risk localized prostate cancer unless the patient has both limited life expectancy and local symptoms. (Strong Recommendation; Evidence Level: Grade
  • Clinicians may consider referral for genetic counseling for patients (and their families) with high-risk localized prostate cancer and a strong family history of specific cancers (eg, breast, ovarian, pancreatic, other gastrointestinal tumors, lymphoma). (Expert Opinion)

European Society of Medical Oncology

The 2015 ESMO guidelines recommend watchful waiting with delayed hormone therapy as an option for localized disease or as an alternative for men with localized or locally advanced disease who are unwilling or unsuited for radical therapy. [206]

Other recommended treatment options include [203] :

  • Active surveillance for men with low-risk disease 

  • Radical prostatectomy (RP) or radiotherapy (external beam or brachytherapy) for men with low- or intermediate-risk disease 

  • Primary androgen deprivation therapy (ADT)  alone is not recommended for treatment of non-metastatic disease 

  • For patients with high-risk or locally advanced prostate cancer, external beam RT plus hormone treatment or RP plus pelvic lymphadenectomy 

Cancer Care Ontario/American Society of Clinical Oncology

In 2016, the American Society of Clinical Oncology (ASCO) endorsed Cancer Care Ontario’s guideline on active surveillance for the management of localized prostate cancer. [207] The recommendations include the following:

  • Active surveillance is the recommended disease management strategy for most patients with low‐risk (Gleason score ≤6) localized prostate cancer.
  • Because of heterogeneity within this population, factors such as younger age, high-volume Gleason 6 cancer, patient preference, and/or African American ethnicity should be taken into account in the decision to use active surveillance.
  • Young patients (under age 55) with high-volume Gleason 6 cancer should be closely scrutinized for the presence of higher‐grade cancer; definitive therapy may be warranted for select patients.
  • For patients with limited life expectancy (< 5 years) and low‐risk cancer, watchful waiting may be more appropriate than active surveillance.
  • Active treatment (radical prostatectomy or radiotherapy) is recommended for most patients with intermediate‐risk (Gleason score 7) localized prostate cancer, but active surveillance may be offered to select patients with low‐volume, intermediate‐risk (Gleason 3+4=7) localized prostate cancer.

The guidelines recommend that the active surveillance protocol include the following tests:

  • Prostate-specific antigen (PSA) testing every 3 to 6 months
  • Digital rectal examination (DRE) at least every year
  • At least a 12-core confirmatory transrectal ultrasound (TRUS)–guidedbiopsy (including anterior directed cores) within 6 to 12 months, then serial biopsy every 2 to 5 years thereafter, or more frequently if clinically warranted; men with limited life expectancy may transition to watchful waiting and avoid further biopsies.
  • Ancillary tests that are still under investigation but may be included in the protocol could include  multiparametric MRI (mpMRI) and/or genomic testing. Such tests may beindicated when a patient’s clinical findings are discordant with the pathologic findings
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Bone Scan for Diagnosis of Metastatic Disease

Current NCCN guidelines include scanning technology utilizing fluorine-18 sodium fluoride (18F-NaF) as the tracer for the subsequent positron-emission tomography (PET) scan as an option for men with prostate cancer who undergo a bone scan to search for metastatic disease. PET and hybrid imaging bone scans appear more sensitive than conventional 99-technetium bone scans. [41]

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Advanced Prostate Cancer

AUA/ASTRO/SUO guidelines on advanced prostate cancer separate management considerations into the following four disease states, which encompass the entire continuum of advanced prostate cancer. [130]

  1. Biochemical recurrence without metastatic disease, after exhaustion of local treatment options
  2. Metastatic hormone-sensitive prostate cancer
  3. Non-metastatic castration-resistant prostate cancer
  4. Metastatic castration-resistant prostate cancer

Management based on these disease states is discussed in the Treatment section. 

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Castration-Resistant Prostate Cancer

The following organizations have published guidelines for the treatment of castration-resistant prostate cancer (CRPC):

  • American Society of Clinical Oncology (ASCO)/Cancer Care Ontario (CCO)

  • American Urology Association (AUA)

  • National Comprehensive Cancer Network (NCCN)

  • European Association of Urology/European Society for Radiotherapy and Oncology/International Society of Geriatric Oncology (EAU/ESTRO/SIOG)

American Society of Clinical Oncology/Cancer Care Ontario recommendations

ASCO and CCO released a joint clinical practice guideline for treatment of men with metastatic CRPC in 2014. The guideline recommendations include the following [208] :

  • Pharmacologic androgen deprivation therapy (ADT) should be continued indefinitely

  • Offer patients one of three treatment options—abiraterone/prednisone, enzalutamide, or radium-223 (if cancer has spread to bone)—in addition to hormone deprivation

  • When considering chemotherapy, docetaxel/prednisone should be an option but side effects must be discussed

  • Offer cabazitaxel to men whose disease worsens even if docetaxel has been tried, but again, discuss side effects

  • Offer sipuleucel-T to men with no symptoms or minimal symptoms of cancer

  • Offer mitoxantrone, but include a discussion of the drug's limited clinical benefit and side effect risk

  • Offer ketoconazole or the anti-androgen therapies bicalutamideflutamide or nilutamide but discuss the limited clinical benefit for these three medications

  • Do not offer the drugs bevacizumab (Avastin), estramustine, or sunitinib

  • Begin discussion of palliative care early on while discussing treatment options

American Urological Association recommendations

American Urological Association guidelines for the management of CRPC describe six index-patient scenarios for which recommendations could be formulated. [208]

Index patient no. 1: Asymptomatic non-metastatic CRPC

Recommendations are as follows:

  • Observation with continued ADT

  • First-generation antiandrogens (flutamide, bicalutamide, and nilutamide) or first-generation androgen-synthesis inhibitors (ketoconazole plus steroid) to patients unwilling to accept observation.

  • Systemic chemotherapy or immunotherapy should not be offered to patients with non-metastatic CRPC outside the context of a clinical trial

Index patient no. 2: Asymptomatic or minimally-symptomatic, metastatic CRPC with good performance status and without prior docetaxel chemotherapy

Recommendations are as follows:

  • Abiraterone plus prednisone, enzalutamide, docetaxel, or sipuleucel-T

  • First-generation antiandrogen therapy or ketoconazole plus steroid or observation to patients who do not want or cannot have one of the standard therapies

Index patient no. 3: Symptomatic, metastatic CRPC with good performance status and no prior docetaxel chemotherapy

Recommendations are as follows:

  • Docetaxel

  • Abiraterone plus prednisone, enzalutamide, or docetaxel

  • Ketoconazole plus steroid, mitoxantrone, or radionuclide therapy for patients who do not want or cannot have one of the standard therapies

  • Radium-223 to patients with symptoms from bony metastases and without known visceral disease

  • Treatment with either estramustine or sipuleucel-T should not be offered

Index patient no. 4: Symptomatic, metastatic CRPC with poor performance status and no prior docetaxel chemotherapy

Recommendations are as follows:

  • Abiraterone plus prednisone or enzalutamide

  • Ketoconazole plus steroid or radionuclide therapy to patients who are unable or unwilling to receive abiraterone plus prednisone

  • Docetaxel or mitoxantrone chemotherapy in select cases, specifically when performance status is directly related to the cancer

  • Radium-223 to patients with symptoms from bony metastases and without known visceral disease in select cases, specifically when the performance status is directly related to symptoms related to bone metastases.

  • Treatment with sipuleucel-T should not be offered

Index patient no. 5: Symptomatic, metastatic CRPC with good performance status and prior docetaxel chemotherapy

Recommendations are as follows:

  • Abiraterone plus prednisone, cabazitaxel, or enzalutamide

  • If the patient received abiraterone plus prednisone prior to docetaxel chemotherapy, offer cabazitaxel or enzalutamide

  • Ketoconazole plus steroid if abiraterone plus prednisone, cabazitaxel, or enzalutamide is unavailable

  • Re-treatment with docetaxel for patients who were benefiting from but discontinued treatment with docetaxel because of reversible adverse effects

  • Radium-223 to patients with symptoms from bony metastases and without known visceral disease

Index patient no. 6: Symptomatic, metastatic CRPC with poor performance status and prior docetaxel chemotherapy

Recommendations are as follows:

  • Palliative care

  • For selected patients, offer treatment with abiraterone plus prednisone, enzalutamide, ketoconazole plus steroid, or radionuclide therapy

  • Systemic chemotherapy or immunotherapy should not be offered

Bone health recommendations

Because the skeletal system is the most common site for prostate cancer metastasis, the guideline also makes recommendations regarding bone health not specific to any index patient group:

  • Offer preventive treatment (eg, supplemental calcium, vitamin D) for fractures

  • Choose either denosumab or zoledronic acid as preventative treatment for skeletal-related events

National Comprehensive Cancer Network recommendations

The NCCN guidelines for prostate cancer include treatment recommendations for CRPC based on the presence or absence of visceral metastases. For the most part, these recommendations are based on high-level evidence and are supported by uniform NCCN consensus (category 1 recommendations). [41]

CRPC without distant metastasis

  • Enrollment in clinical trial is preferred

  • Observation is acceptable

  • Secondary hormone therapy can be considered for patients with prostate-specific antigen (PSA) doubling < 10 months; anti-androgen therapy is acceptable for patients who previously received medical or surgical castration, ketoconazole, corticosteroids, diethylstilbestrol or other estrogens

CRPC with bone metastases

Measures to promote bone health include the following:

  • Zoledronic acid or denosumab

  • Avoidance of invasive dental surgery during treatment

  • Calcium and vitamin D supplements to prevent hypocalcemia during treatment

Radium-233 can be used to treat symptomatic bone metastases without visceral metastases.

Metastatic CRPC with no visceral metastases

  • Sipuleucel-T for asymptomatic or minimally symptomatic patients

  • Abiraterone plus prednisone or enzalutamide for asymptomatic patients

  • Docetaxel with prednisone for symptomatic patients; may also be considered in a symptomatic patients with signs of rapid progression

  • Radium-233 for symptomatic patients

  • Secondary hormone therapy or enrollment in clinical trial may be considered

Second-line treatment for patients with no visceral metastases who experience progression of disease after treatment with enzalutamide or abiraterone is as follows:

  • Docetaxel with prednisone

  • Abiraterone, if the patient had previously taken enzalutamide

  • Enzalutamide, if the patient had previously taken abiraterone

  • Radium-233 for bone-predominant disease

  • Sipuleucel-T for asymptomatic or minimally symptomatic patients with no liver metastases, life expectancy > 6 mo, and ECOG performance status 0-1

  • Clinical trial

  • Other secondary hormone therapy (eg, antiandrogen, antiandrogen withdrawal, ketoconazole, corticosteroids, diethylstilbestrol or other estrogen)

  • Best supportive care

Second-line treatment for patients with no visceral metastases who experience progression of disease after treatment with docetaxel is as follows:

  • Enzalutamide

  • Abiraterone with prednisone

  • Radium-233 for bone-predominant disease

  • Cabazitaxel with prednisone

  • Sipuleucel-T for asymptomatic or minimally symptomatic patients with no liver metastases, life expectancy > 6 mo, and ECOG performance status 0-1

  • Clinical trial

  • Docetaxel rechallenge

  • Alternative chemotherapy (mitoxantrone)

  • Other secondary hormone therapy (eg, antiandrogen, antiandrogen withdrawal, ketoconazole, corticosteroids, diethylstilbestrol or other estrogen)

  • Best supportive care

Metastatic CRPC with visceral metastases

  • Docetaxel with prednisone (preferred treatment)

  • Addition of estramustine to docetaxel not recommended

  • Enzalutamide (category 1)

  • Abiraterone for men who decline chemotherapy

Second-line treatment for patients with visceral metastases who experience progression of disease after treatment with enzalutamide or abiraterone is as follows:

  • Docetaxel with prednisone

  • Clinical trial

  • Abiraterone, if the patient had previously taken enzalutamide

  • Enzalutamide, if the patient had previously taken abiraterone

  • Other secondary hormone therapy (eg, antiandrogen, antiandrogen withdrawal, ketoconazole, corticosteroids, diethylstilbestrol or other estrogen)

  • Best supportive care

Second-line treatment for patients with visceral metastases who experience progression of disease after treatment with docetaxel is as follows:

  • Enzalutamide

  • Abiraterone with prednisone

  • Cabazitaxel with prednisone

  • Clinical trial

  • Docetaxel rechallenge

  • Alternative chemotherapy (mitoxantrone)

  • Other secondary hormone therapy (eg, antiandrogen, antiandrogen withdrawal, ketoconazole, corticosteroids, diethylstilbestrol or other estrogen)

  • Best supportive care

Metastatic CRPC with pathogenic mutations

  • Olaparib, for patients with a pathogenic mutation (germline and/or somatic) in a homologous recombination repair gene (BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D or RAD54L) who have been treated with androgen receptor–directed therapy. However, olaparib is not recommended in patients with a PPP2R2A mutation.

  • Rucaparib, for patients with a pathogenic BRCA1 or BRCA2 mutation (germline and/or somatic) who have been treated with androgen receptor–directed therapy and taxane-based chemotherapy. If the patient is not fit for chemotherapy, rucaparib can be considered even if taxane-based therapy has not been given.

European Association of Urology/European Society for Radiotherapy and Oncology/International Society of Geriatric Oncology recommendations

EAU, ESTRO and SIOG released a joint clinical practice guideline for prostate cancer in 2016. The guideline recommendations for patients with mCRPC  include the following [205] :

  • Treat with life prolonging agents (alphabetical order: abiraterone, docetaxel, enzalutamide, radium-223, sipuleucel-T). Base the choice of first line treatment on the performance status, symptoms, comorbidities and extent of disease.

  • Candidates for cytotoxic therapy should be offered docetaxel with 75 mg/m2 every 3 weeks.

  • In patients with progression following docetaxel chemotherapy, offer further life-prolonging treatment options, which include cabazitaxel, abiraterone, enzalutamide and radium-223.

  • Offer bone protective agents to patients with skeletal metastases to prevent osseous complications. However, the benefits must be balanced against the toxicity of these agents, and jaw necrosis, in particular, must be avoided.

  • Offer calcium and vitamin D supplementation when prescribing either denosumab or bisphosphonates.

  • Treat painful bone metastases early on with palliative measures such as EBRT, radionuclides, and adequate use of analgesics.

  • In patients with spinal cord compression, start immediate high-dose corticosteroids and assess for spinal surgery followed by irradiation. Offer radiation therapy alone if surgery is not appropriate.

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Imaging in Advanced Prostate Cancer

Guidelines from the American Society of Clinical Oncology recommend imaging for all patients with advanced prostate cancer, using one or more of the following modalities, according to the clinical scenario [209] :

  • Conventional imaging – Computed tomography (CT), bone scan, prostate magnetic resonance imaging (MRI)
  • Next-generation imaging (NGI) – Positron emission tomography (PET), PET/CT, PET/MRI, whole-body MRI)

Disease states and clinical scenarios should be taken into consideration when choosing an imaging modality, as the modality may guide treatment or change clinical treatment decisions.

Newly diagnosed clinically high-risk/very-high-risk localized prostate cancer

When conventional imaging is negative in patients with a high risk of metastatic disease, NGI may add clinical benefit, although prospective data are limited.

When conventional imaging is suspicious or equivocal, NGI may be offered to patients for clarification of equivocal findings or detection of additional sites of disease, which could potentially alter management, although prospective data are limited.

Rising prostate-specific antigen level after prostatectomy and negative conventional imaging

When the prostate-specific antigen (PSA) level is initially undetectable but subsequently rises, or the PSA level never nadirs to undetectable, this indicates potentially undetected residual local, locoregional, or micrometastatic disease; imaging options are not distinct or different between those scenarios. The goal of therapy and the potential use of salvage local therapies in these scenarios should guide the choice of imaging. For men who are not candidates or are unwilling to receive salvage local or regional therapy, additional NGI should not be offered.

For men for whom salvage radiotherapy is contemplated, NGI should be offered. Imaging with new radiopharmaceuticals coupled to prostate cancer–specific targets, such as prostate-specific membrane antigen (PSMA), where available; 11C-choline or 18F-fluciclovine PET/CT; or PET/MRI, whole-body MRI, and/or 18F-NaF PET/CT have superior disease detection performance characteristics and may alter management.

Rising PSA after radiotherapy and negative conventional imaging

For men for whom salvage local or regional therapy is not planned or is inappropriate, there is little evidence that NGI will alter treatment or prognosis. The role of NGI in this scenario is unclear and it should not be offered, except in the context of an institutional review board–approved clinical trial.

For men for whom salvage local or regional therapy (eg, salvage prostatectomy, salvage ablative therapy, or salvage lymphadenectomy) is contemplated, evidence supports NGI for detection of local and/or distant sites of disease. Findings on NGI could guide management in this setting (eg, salvage local, systemic or targeted treatment of metastatic disease, combined local and metastatic therapy). PSMA imaging (where available), 11C-choline or 18F-fluciclovine PET/CT or PET/MRI, whole-body MRI, and/or 18F-NaF PET/CT can provide superior disease detection compared with conventional imaging and their results may alter patient management, although data are limited.

Hormone- sensitive metastatic prostate cancer at initial diagnosis or after initial treatment

In the initial evaluation of men presenting with hormone-sensitive metastatic disease that is demonstrable on conventional imaging, NGI has a potential role in clarifying the burden of disease and potentially shifting the treatment intent from multimodality management of oligometastatic disease to systemic anticancer therapy alone or in combination with targeted therapy for palliative purposes. However, prospective data are limited.

Nonmetastatic castration-resistant prostate cancer

For men with nonmetastatic castration-resistant prostate cancer (CRPC), NGI can be offered only if a change in the clinical care is contemplated. Assuming patients have received or are ineligible for local salvage treatment options, NGI may clarify the presence or absence of metastatic disease, but the data on detection capabilities of NGI in this setting and impact on management are limited.

Metastatic CRPC

Because PSA progression alone should not be the sole reason to change therapy in men with metastatic CRPC, conventional imaging can be used for initial evaluation of PSA progression and should be continued to facilitate changes/comparisons and serially to assess for development of radiographic progression.

The use of NGI in this cohort is unclear, with a paucity of prospective data. When a change in clinical care is contemplated, in an individualized manner, and there is a high clinical suspicion of subclinical metastasis despite negative conventional imaging, the use of NGI could be contemplated, especially in the setting of a clinical trial.

In men who are receiving systemic therapy for metastatic CRPC and have clear evidence of radiographic progression on conventional imaging, NGI should not be routinely offered. NGI may play a role, if it had been performed at baseline, to facilitate comparison of imaging findings/extent of progression of disease.

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