Last updated December 18, 2021

Initial Management of Noncastrate Adavanced, Recurrent, or Metastatic Prostate Cancer

Recommendations

Initial Treatment

1.0 Docetaxel, abiraterone, enzalutamide, or apalutamide, each when administered with ADT, represent four separate standards of care (SOCs) for noncastrate metastatic prostate cancer. The use of any of these agents in any particular combination or in any particular series cannot yet be recommended. 
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Androgen Deprivation Therapy (ADT) Plus Docetaxel

1.1 For men with metastatic noncastrate prostate cancer with high-volume disease (HVD) as defined per CHAARTED who are candidates for treatment with chemotherapy, the addition of docetaxel to ADT should be offered. 

(Strong recommendation [for patients with HVD])

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1.2 For patients with low-volume metastatic disease (LVD) as defined per CHAARTED who are candidates for chemotherapy, docetaxel plus ADT should NOT be offered. 

(Strong recommendation [for patients with LVD)

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1.3 The recommended regimen of docetaxel for men with metastatic noncastrate prostate cancer is six doses administered at 3 week intervals at 75 mg/m2 either alone (per CHAARTED) or with prednisolone (per STAMPEDE).
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ADT Plus Abiraterone

1.4 For men with high-risk de novo metastatic noncastrate prostate cancer, the addition of abiraterone to ADT should be offered per LATITUDE.
(Strong recommendation [for patients with high-risk disease as defined per LATITUDE)
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1.5 For men with low-risk de novo metastatic noncastrate prostate cancer, ADT plus abiraterone may be offered per STAMPEDE.

[for patients with low-risk disease per STAMPEDE]).

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1.6 The recommended regimen for men with metastatic noncastrate prostate cancer is abiraterone 1,000 mg with either prednisolone or prednisone 5 mg once daily until progressive disease is documented.
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ADT Plus Enzalutamide

1.7 ADT plus enzalutamide should be offered to men with metastatic noncastrate prostate cancer including both those with de novo metastatic disease and those who have received prior therapies, such as radical prostatectomy or radiotherapy for localized disease. Enzalutamide plus ADT has demonstrated short-term survival benefits (PSA progression-free, clinical progression-free, and overall) when compared to ADT alone for men with metastatic noncastrate prostate cancer as a group per ENZAMET.
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1.8 The recommended regimen for men with metastatic noncastrate prostate cancer is enzalutamide (160 mg per day) with ADT.
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ADT Plus Apalutamide 

1.9 ADT plus apalutamide should also be offered to men with metastatic noncastrate prostate cancer, including those with de novo metastatic disease or those who have received prior therapy, such as radical prostatectomy or radiotherapy for localized disease per TITAN.
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1.95 The recommended regimen for men with metastatic noncastrate prostate cancer is apalutamide (240 mg per day) with ADT.
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Combination Therapies

2.1 ADT plus abiraterone and prednisolone should be considered for men with noncastrate locally advanced non-metastatic prostate cancer, rather than castration monotherapy, due to the failure-free survival benefit per STAMPEDE. Radiotherapy to the primary was mandated in STAMPEDE for patients with newly diagnosed node-negative, non-metastatic disease and encouraged in patients with newly diagnosed node-positive, non-metastatic disease. Failure-free survival (time to the earliest of biochemical failure, disease progression, or death), was significantly improved for patients with non-metastatic disease treated with ADT plus abiraterone and prednisolone compared to those treated with ADT alone, even though ADT plus abiraterone was administered for two or less years to men with non-metastatic disease.
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2.2 In resource-constrained settings where drugs such as abiraterone may not be available, combined androgen blockade using ADT plus a first-generation antiandrogen, such as flutamide, nilutamide, or bicalutamide, may be offered to men with locally advanced non-metastatic prostate cancer, rather than castration monotherapy based on recent meta-analyses.
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Early Androgen Deprivation

3.1 Early (immediate) ADT may be offered to men who initially present with noncastrate locally advanced non-metastatic disease who have not undergone previous local treatment and are unwilling or unable to undergo radiotherapy based on evidence in one meta-analysis of a modest but statistically significant benefit in terms of both overall survival and cancer-specific survival among the larger population of men with locally advanced non-metastatic disease. 
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Intermittent Androgen Deprivation 

4.1 Intermittent therapy may be offered to men with high-risk biochemically recurrent non-metastatic prostate cancer after RP and/or RT based on evidence in meta-analyses of the non-inferiority of intermittent androgen deprivation therapy (IADT) when compared to continuous androgen deprivation therapy (CADT) with respect to overall survival. This is further supported by evidence from four meta-analyses testing superiority. Low-risk biochemical recurrence after radical prostatectomy is defined as a PSA doubling time >1 year and pathologic Gleason score <8. Low-risk biochemical recurrence after radiotherapy is defined as an interval to biochemical recurrence >18 months and clinical Gleason score <8. High-risk biochemical recurrence after radical prostatectomy is defined as a PSA doubling time <1 year or a pathologic Gleason score of 8–10. High-risk biochemical recurrence after radiotherapy is defined as an interval to biochemical recurrence <18 months or a clinical Gleason score of 8–10. Active surveillance may be offered to men with low-risk biochemically recurrent non-metastatic prostate cancer.
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Recommendation Grading

Overview

Title

Initial Management of Noncastrate Adavanced, Recurrent, or Metastatic Prostate Cancer

Authoring Organization

Publication Month/Year

January 1, 2021

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Male, Adult, Older adult

Health Care Settings

Ambulatory, Home health, Hospital

Intended Users

Social worker, physician, nurse

Scope

Management

Diseases/Conditions (MeSH)

D011467 - Prostate

Keywords

recurrent, Metastatic Prostate Cancer, Clinical guidelines, Noncastrate Advanced, Immediate ADT, Intermittent ADT