Advanced Prostate Cancer

Publication Date: April 25, 2023
Last Updated: April 26, 2023

Guideline Statements

Early Evaluation and Counseling

In patients with suspicion of advanced prostate cancer and no prior histologic confirmation, clinicians should obtain tissue diagnosis from the primary tumor or site of metastases when clinically feasible. (Clinical Principle, )
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Clinicians should discuss treatment options with advanced prostate cancer patients based on life expectancy, comorbidities, preferences, and tumor characteristics. Patient care should incorporate a multidisciplinary approach when available. (Clinical Principle, )
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Clinicians should optimize pain control or other symptom support in advanced prostate cancer patients and encourage engagement with professional or community-based resources, including patient advocacy groups. (Clinical Principle, )
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Biochemical Recurrence without Metastatic Disease after Exhaustion of Local Treatment Options

Prognosis

Clinicians should inform patients with PSA recurrence after exhaustion of local therapy regarding the risk of developing metastatic disease and follow such patients with serial PSA measurements and clinical evaluation. Clinicians may consider radiographic assessments based on overall PSA and PSA kinetics. (Clinical Principle, )
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In patients with PSA recurrence after failure of local therapy who are at higher risk for the development of metastases (eg, PSADT <12 months), clinicians should perform periodic staging evaluations consisting of cross-sectional imaging (CT, MRI) and technetium bone scan, and/or preferably PSMA PET imaging. (Clinical Principle, )
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Clinicians should utilize PSMA PET imaging preferentially, where available, in patients with PSA recurrence after failure of local therapy as an alternative to conventional imaging due to its greater sensitivity, or in the setting of negative conventional imaging. (Expert Opinion, )
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Treatment

For patients with a rising PSA after failure of local therapy and no demonstrated metastatic disease by imaging, clinicians should offer observation or clinical trial enrollment. (Clinical Principle, )
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ADT should not be routinely initiated in this population (Expert Opinion). However, if ADT is initiated in the absence of metastatic disease, intermittent ADT may be offered in lieu of continuous ADT. (RecommendationB)
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Metastatic Hormone-Sensitive Prostate Cancer

Prognosis

Clinicians should assess the extent of metastatic disease (lymph node, bone and visceral metastasis) in newly diagnosed mHSPC patients. (Clinical Principle, )
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In newly diagnosed mHSPC patients, clinicians should assess the extent of metastatic disease (low- versus high-volume). High-volume is defined as greater than or equal to four bone metastases with at least one metastasis outside of the spine/pelvis and/or the presence of visceral metastases. (Moderate, B)
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Clinicians should assess if a newly diagnosed mHSPC patient is experiencing symptoms from metastatic disease at the time of presentation to guide discussions of prognosis and further disease management. (Recommendation, B)
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Clinicians should obtain a baseline PSA and serial PSAs at three- to six-month intervals after initiation of ADT in mHSPC patients and consider periodic conventional imaging. (Clinical Principle, )
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In patients with mHSPC, clinicians should offer germline testing, and consider somatic testing and genetic counseling. (Clinical Principle, )
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Treatment

Clinicians should offer ADT with either LHRH agonists or antagonists or surgical castration in patients with mHSPC. (StandardB)
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In patients with mHSPC, clinicians should offer ADT in combination with either androgen pathway directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel). (Strong, A)
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In selected mHSPC patients with low-volume metastatic disease, clinicians may offer primary radiotherapy to the prostate in combination with ADT. (Moderate, C)
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Clinicians should not offer first generation antiandrogens (bicalutamide, flutamide, nilutamide) in combination with LHRH agonists in patients with mHSPC, except to block testosterone flare. (StandardA)
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Clinicians should not offer oral androgen pathway directed therapy (e.g., abiraterone acetate plus prednisone, apalutamide, bicalutamide, darolutomide, enzalutamide, flutamide, nilutamide) without ADT for patients with mHSPC. (Expert Opinion, )
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In selected patients with de novo mHSPC, clinicians should offer ADT in combination with docetaxel and either
abiraterone acetate plus prednisone (Strong, A)
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darolutamide (Strong, B)
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Non-Metastatic Castration-Resistant Prostate Cancer

Prognosis

In nmCRPC patients, clinicians should obtain serial PSA measurements at three- to six-month intervals, and calculate a PSADT starting at the time of development of castration-resistance. (Clinical Principle, )
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Clinicians should assess nmCRPC patients for development of metastatic disease using conventional or PSMA PET imaging at intervals of 6 to 12 months. (Expert Opinion, )
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Treatment

Clinicians should offer apalutamide, darolutamide, or enzalutamide with continued ADT to nmCRPC patients at high risk for developing metastatic disease (PSADT ≤10 months). (StandardA)
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Clinicians may recommend observation with continued ADT to nmCRPC patients, particularly those at lower risk (PSADT >10 months) for developing metastatic disease. (Clinical Principle, )
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Clinicians should not offer systemic chemotherapy or immunotherapy to nmCRPC patients outside the context of a clinical trial. (Clinical Principle, )
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Metastatic Castration-Resistant Prostate Cancer

Prognosis

In mCRPC patients, clinicians should obtain baseline labs (e.g., PSA, testosterone, LDH, Hgb, alkaline phosphatase level) and review location of metastatic disease (bone, lymph node, visceral), disease-related symptoms, and performance status to inform discussions of prognosis and treatment decision making. (Clinical Principle, )
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In mCRPC patients, clinicians should assess the extent of metastatic disease using conventional imaging at least annually or at intervals determined by lack of response to therapy. (Expert Opinion, )
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In patients with mCRPC, clinicians should offer germline (if not already performed) and somatic genetic testing to identify DNA repair deficiency, microsatellite instability (MSI) status, tumor mutational burden, and other potential mutations that may inform prognosis and familial cancer risk as well as direct potential targeted therapies. (Clinical Principle, )
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In mCRPC patients without PSA progression or new symptoms, clinicians should perform imaging at least annually. (Expert Opinion, )
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In mCRPC patients with disease progression (PSA or radiographic progression or new disease related symptoms) having previously received docetaxel and androgen pathway inhibitor, who are considering Lu-PSMA-617, clinicians should order PSMA PET imaging. (Expert Opinion, )
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Treatment

In newly diagnosed mCRPC patients who have not received prior androgen receptor pathway inhibitors, clinicians should offer continued ADT with
abiraterone acetate plus prednisone (Strong, A)
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docetaxel (Strong, B)
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enzalutamide. (Strong, A)
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In mCRPC patients who are asymptomatic or minimally symptomatic, clinicians may offer sipuleucel-T. (RecommendationB)
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Clinicians should offer radium-223 to patients with symptoms from bony metastases from mCRPC and without known visceral disease or lymphadenopathy >3cm. (StandardB)
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In sequencing agents, clinicians should consider prior treatment and consider recommending therapy with an alternative mechanism of action. (Moderate, B)
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In mCRPC patients who received prior docetaxel chemotherapy with or without prior abiraterone acetate plus prednisone or enzalutamide for the treatment of CRPC, clinicians may offer cabazitaxel. (Moderate, B)
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In mCRPC patients who received prior docetaxel chemotherapy and abiraterone acetate plus prednisone or enzalutamide, clinicians should recommend cabazitaxel rather than an alternative androgen pathway directed therapy. (StandardB)
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Clinicians should offer a PARP inhibitor to patients with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated mCRPC following prior treatment with enzalutamide or abiraterone acetate, and/or a taxane-based chemotherapy. Platinum based chemotherapy may be offered as an alternative for patients who cannot use or obtain a PARP inhibitor. (RecommendationC)
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In patients with mismatch repair deficient or microsatellite instability high mCRPC, clinicians should offer pembrolizumab. (Moderate, C)
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Clinicians should offer Lu-PSMA-617 to patients with progressive mCRPC having previously received docetaxel and androgen pathway inhibitor with a positive PSMA PET imaging study. (Strong, B)
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Bone Health

Clinicians should discuss the risk of osteoporosis associated with ADT and should assess the risk of fragility fracture in patients with advanced prostate cancer. (Clinical Principle, )
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Clinicians should recommend preventative treatment for fractures and skeletal-related events, including supplemental calcium, vitamin D, smoking cessation, and weight-bearing exercise, to advanced prostate cancer patients on ADT. (Clinical Principle, )
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In advanced prostate cancer patients at high fracture risk due to bone loss, clinicians should recommend preventative treatments with bisphosphonates or denosumab and referral to physicians who have familiarity with the management of osteoporosis when appropriate. (Clinical Principle, )
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Clinicians should prescribe a bone-protective agent (denosumab or zoledronic acid) for mCRPC patients with bony metastases to prevent skeletal-related events. (RecommendationB)
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Recommendation Grading

Overview

Title

Advanced Prostate Cancer

Authoring Organizations

American Urological Association

Society of Urologic Oncology

Publication Month/Year

April 25, 2023

Last Updated Month/Year

September 3, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Home health, Hospice, Hospital

Intended Users

Nurse, nurse practitioner, physician, physician assistant, social worker

Scope

Counseling, Diagnosis, Assessment and screening, Treatment, Management, Prevention

Diseases/Conditions (MeSH)

D011467 - Prostate

Keywords

Advanced Prostate Cancer, Castration-resistant Prostate cancer, Non-metastatic castration-resistant prostate cancer, Metastatic hormone-sensitive prostate cancer

Source Citation

Lowrance W, Dreicer R, Jarrard DF, Scarpato KR, Kim SK, Kirkby E, Buckley DI, Griffin JC, Cookson MS. Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023). J Urol. 2023 Apr 25:101097JU0000000000003452. doi: 10.1097/JU.0000000000003452. Epub ahead of print. PMID: 37096583.

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
173
Literature Search Start Date
January 5, 1998
Literature Search End Date
January 20, 2020