Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II
2020; Lippincott Williams & Wilkins; Volume: 205; Issue: 1 Linguagem: Inglês
10.1097/ju.0000000000001376
ISSN1527-3792
AutoresWilliam T. Lowrance, Rodney H. Breau, Roger Chou, Brian F. Chapin, Tony Crispino, Robert Dreicer, David F. Jarrard, Adam S. Kibel, Todd M. Morgan, Alicia K. Morgans, William Oh, Matthew J. Resnick, Anthony L. Zietman, Michael S. Cookson,
Tópico(s)Economic and Financial Impacts of Cancer
ResumoYou have accessJournal of UrologyAUA Guideline1 Jan 2021Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II William T. Lowrance,*, Rodney H. Breau, Roger Chou, Brian F. Chapin, Tony Crispino, Robert Dreicer, David F. Jarrard, Adam S. Kibel, Todd M. Morgan, Alicia K. Morgans, William K. Oh, Matthew J. Resnick, Anthony L. Zietman, and Michael S. Cookson William T. Lowrance,*William T. Lowrance,* More articles by this author , Rodney H. BreauRodney H. Breau More articles by this author , Roger ChouRoger Chou More articles by this author , Brian F. ChapinBrian F. Chapin More articles by this author , Tony CrispinoTony Crispino More articles by this author , Robert DreicerRobert Dreicer More articles by this author , David F. JarrardDavid F. Jarrard More articles by this author , Adam S. KibelAdam S. Kibel More articles by this author , Todd M. MorganTodd M. Morgan More articles by this author , Alicia K. MorgansAlicia K. Morgans More articles by this author , William K. OhWilliam K. Oh More articles by this author , Matthew J. ResnickMatthew J. Resnick More articles by this author , Anthony L. ZietmanAnthony L. Zietman More articles by this author , and Michael S. CooksonMichael S. Cookson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001376AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. Results: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1 Figure 1. Statement Summary and detailed herein. Materials and Methods: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. Conclusions: This guideline attempts to improve a clinician’s ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients. Abbreviations and Acronyms ADT Androgen deprivation therapy AR Androgen receptor ART Androgen receptor-targeted therapy CRPC Castration-resistance prostate cancer CT Computed tomography mCRPC Metastatic castration-resistance prostate cancer MFS Metastasis-free survival MRI Magnetic resonance imaging nmCRPC Non-metastatic castration-resistance prostate cancer OS Overall survival PET Positron emission tomography PSA Prostate specific antigen PSADT Prostate specific antigen doubling time SRE Skeletal-related event Castration-resistant prostate cancer (CRPC), whether metastatic (mCRPC) or non-metastatic (nmCRPC), generally occurs in response to therapeutic pressure, specifically the use of androgen deprivation therapy (ADT). The exact mechanism of transition from hormone-sensitive to castration-resistant disease is still not fully understood, and some disease may be inherently resistant at presentation. However, it is clear that despite castrate levels of androgens, the androgen receptor (AR) remains active and continues to drive prostate cancer progression in most cancers.1,2 As such, multiple agents have been developed that further decrease androgen production or block AR signaling in addition to standard ADT with luteinizing hormone-releasing hormone agonists or antagonists. It is hypothesized that there are additional biologic pathways that function independently of androgen signaling resulting in CRPC. With a greater understanding of tumor biology, there is hope for continued development of innovative treatment options that further improve survival for men with CRPC. For a full description of the methodology used in the development of guideline statements, refer to the unabridged guideline available at www.auanet.org/guidelines. Guideline Statements Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) Men with a rising prostate specific antigen (PSA) but no visible metastatic disease on conventional imaging despite medical or surgical castration represent a uniquely distinct disease state. The advent of improved imaging, including next generation positron emission tomography (PET)- computed tomography (CT) scanning, has allowed for the discovery of small volume metastases that were previously undetected with standard clinical imaging such as bone scans, CT, and magnetic resonance imaging (MRI). Nevertheless, there remains a subset of patients whose disease remains defined by biochemical PSA rise only. Until recently there have been no agents specifically FDA approved for the treatment of men with nmCRPC. However, three AR antagonists successfully prolonged metastasis-free survival (MFS), defined as the development of metastases or death from any cause, when compared with ADT plus placebo in men with nmCRPC.3–5 Prognosis 19. In nmCRPC patients, clinicians should obtain serial PSA measurements at three- to six-month intervals, and calculate a PSA doubling time (PSADT) starting at the time of development of castration-resistance. (Clinical Principle) 20. Clinicians should assess nmCRPC patients for development of metastatic disease using conventional imaging at intervals of 6 to 12 months. (Expert Opinion) Monitoring of men with nmCRPC should include serial measurements of PSA, whether patients are receiving ADT alone or ADT with an additional AR directed therapy (apalutamide, darolutamide, enzalutamide). PSADT should be calculated for men with a rising PSA in the setting of ongoing ADT (castration-resistance) as PSADT is useful in determining which men are at highest risk of developing metastatic lesions or dying from prostate cancer.6 PSADT ≤10 months was used to identify the highest risk population for inclusion in the three trials that led to approval of the AR antagonists for men with nmCRPC and is recommended to consider when adding one of the medications to ADT in men with nmCRPC.3–5 In addition to monitoring PSA, routine use of conventional imaging should be integrated into monitoring the disease status of men with nmCRPC. The suggested interval of conventional imaging is 6 to 12 months, with the exact interval determined by the PSADT calculation, the development of symptoms, and patient/physician preference. Treatment 21. Clinicians should offer apalutamide, darolutamide, or enzalutamide with continued ADT to nmCRPC patients at high risk for developing metastatic disease (PSADT ≤10 months). (Strong Recommendation; Evidence Level Grade A) Apalutamide In the double-blind, placebo-controlled, Phase 3 SPARTAN trial,4 Smith et al. randomly assigned 1,207 men (2:1) to receive apalutamide or placebo. At the time of planned primary analysis, median MFS was 40.5 months in the apalutamide group compared to 16.2 months in the placebo group (HR=0.28; 95% CI 0.23–0.35; p <0.001). Median overall survival (OS) was not reached in the apalutamide group versus 39.0 months in the placebo group (HR=0.70; 95% CI 0.47–1.04; p=0.07). Darolutamide The randomized, double-blind, placebo-controlled, Phase 3 ARAMIS study5 randomized 1,509 patients (2:1) to ADT with darolutamide or ADT with placebo. The median MFS was 40.4 months with darolutamide versus 18.4 months with placebo (HR=0.41; 95% CI 0.34–0.50; p <0.001). Median OS was not reached in either group. Enzalutamide The double-blind, placebo-controlled, Phase 3 PROSPER study3 randomized 1,401 patients (2:1) to enzalutamide or placebo. Both arms continued ADT. As of June 2017, a total of 219 patients (23%) in the enzalutamide group had metastases or had died, as compared with 228 (49%) in the placebo group. Median MFS was 36.6 months in the enzalutamide arm compared to 14.7 months in the placebo group (HR=0.29; 95% CI 0.24–0.35; p 10 months) for developing metastatic disease. (Clinical Principle) 23. Clinicians should not offer systemic chemotherapy or immunotherapy to nmCRPC patients outside the context of a clinical trial. (Clinical Principle) It is the Panel’s judgment that observation with continued ADT is recommended for patients with a PSADT >10 months. These patients have a lower risk of developing metastatic disease than patients with a PSADT ≤10 months.8 The Panel strongly recommends against the use of chemotherapy, immunotherapy, or other agents not FDA approved for use in the nmCRPC setting. There is a lack of evidence suggesting benefit, and these agents, like any medication, have associated toxicity. The combination of no known benefit with known and potentially serious harms supports the decision to recommend against use of these agents in men with nmCRPC. Metastatic Castration-Resistant Prostate Cancer (mCRPC) The treatment of men with mCRPC has dramatically changed over the past decade. Prior to 2004, once primary androgen deprivation failed to control the disease, treatments were administered solely for palliation. Landmark studies by Tannock et al. and Petrylak et al. demonstrated that docetaxel improved survival and quality of life for such patients with mCRPC.9,10 Since the approval of docetaxel, multiple additional agents that show a survival benefit have been FDA approved on the basis of randomized controlled trials.1–15 These agents have been tested in multiple “disease states” of mCRPC, both before and after docetaxel chemotherapy, to determine when patients might benefit from each treatment. Prognosis 24. In mCRPC patients, clinicians should obtain baseline labs (eg, PSA, testosterone, lactate dehydrogenase, hemoglobin, 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) There are established laboratory and imaging characteristics known to be associated with prognosis among men with mCRPC. Known laboratory risk-factors associated with increasing risk of mortality include elevated lactate dehydrogenase, testosterone <20-50 ng/dL, higher PSA, and shorter PSADT.16–20 There are established imaging findings also known to be associated with increasing risk of mortality. Increasing burden of metastatic disease in the form of the number of metastatic sites is associated with increasing risk of overall mortality.21 Additionally, there are known relationships between location of metastases and risk of mortality.22 Specifically, visceral metastases are known to portend the highest risk of mortality (HR=1.76; 95% CI 1.34–2.32 versus lymph node) followed by bone metastases (HR=1.52; 95% CI 1.20–1.93 versus lymph node).23 25. 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) It is recommended that men with mCRPC undergo conventional imaging at least annually owing to the fact that in the PREVAIL trial, radiographic progression without PSA progression occurred in 24.5% of mCRPC patients treated with enzalutamide prior to chemotherapy. This suggests that routine imaging can identify a significant portion of patients with radiographic progression who would otherwise not be identified.24 The precise timing of imaging among men with mCRPC should be determined by multiple factors including biochemical response to treatment, change in disease-related symptoms, and patient preference. Furthermore, clinicians should consider known differences in biochemical response to treatment among different therapies for mCRPC when determining the interval between imaging studies. 26. In patients with mCRPC, clinicians should offer germline and somatic tumor genetic testing to identify DNA repair deficiency mutations and microsatellite instability status that may inform prognosis and counseling regarding family risk as well as potential targeted therapies. (Expert Opinion) Germline mutations in genes involved in DNA damage repair have been identified in over 11.8% of men with metastatic prostate cancer.25 Germline mutations have been found to portend poor prognosis among men with metastatic prostate cancer. Specifically, cancer-specific survival among men found to be harboring a BRCA2 mutation was found to be half of that among men without a defect in DNA damage repair (17.4 months versus 33.2 months, p=0.027).26 Mutations in tumor suppressor genes have also been found to be associated with adverse outcomes among men with prostate cancer. Specifically, the presence of one or more mutations in tumor suppressor genes was found to be associated with increasing risk of death among men with metastatic disease. Treatment 27. In newly diagnosed mCRPC patients, clinicians should offer continued ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide. (Strong Recommendation; Evidence Level: Grade A [abiraterone acetate plus prednisone and enzalutamide]/B [docetaxel]) Abiraterone Acetate In the placebo-controlled, double-blind, phase 3 COU-AA-302 study,27 Ryan et al. randomized 1,088 men with mCRPC who had not received prior chemotherapy to receive either abiraterone acetate plus prednisone or placebo plus prednisone. Participants randomized to receive abiraterone acetate plus prednisone had statistically significant improvement in radiographic progression free survival (HR=0.53; 95% CI 0.45–0.62; p <0.001), as previously reported during interim analyses.27 The final analysis of OS showed a statistically significant increase in patients treated with abiraterone acetate plus prednisone (HR=0.81; 95% CI 0.70–0.93; p=0.0033).28 In the COU-AA-301 trial,12 de Bono et al. randomly assigned 1,195 patients who had previously received docetaxel (2:1) to receive prednisone with either abiraterone acetate or placebo. After a median follow-up of 12.8 months, OS was 14.8 months in the abiraterone acetate group compared to 10.9 months in the placebo group (HR=0.65; 95% CI 0.54–0.77; p <0.001). Enzalutamide In the double-blind, phase 3 PREVAIL study,29 Beer et al. randomized 1,717 chemotherapy-naïve patients to receive either enzalutamide or placebo. The results showed that enzalutamide significantly decreased the risk of radiographic progression (HR=0.19; 95% CI 0.15–0.23; p <0.001) and death (29% reduction in the risk of death; HR =0.71; 95% CI 0.60–0.84; p <0.001). In the phase 3, double blind AFFIRM study,11 Scher et al. stratified 1,199 men with CRPC after chemotherapy (2:1) to receive enzalutamide or placebo. At the time of planned interim analysis, the median OS was 18.4 months in the enzalutamide group versus 13.6 months in the placebo group (HR for death in the enzalutamide group=0.63; 95% CI 0.53–0.75; p 3 cm. (Strong Recommendation; Evidence Level: Grade B) The phase 3 ALSYMPCA trial15 studied radium-223 in symptomatic men with progressive mCRPC with or without prior docetaxel exposure and no evidence of visceral metastasis. The trial reported improvement in median overall survival; 14.9 months versus 11.3 months (HR=0.70; 95% CI 0.58–0.83; p <0.001) in favor of radium-223 over placebo. Time to first skeletal-related event (SRE) improved from 9.8 month with placebo to 15.6 months with radium-223 (HR=0.66; 95% CI 0.52–0.83; p <0.001). 30. In sequencing agents, clinicians should consider prior treatment and consider recommending therapy with an alternative mechanism of action. (Moderate Recommendation; Evidence Level: Grade B) Optimal sequencing of agents in mCRPC remains an understudied area of research. As most of the agents approved for mCRPC were studied contemporaneously, the control arms typically were inactive agents such as prednisone or mitoxantrone. The largest trial evaluating the sequencing of two androgen receptor-targeted therapies (ART) was performed in Canada and was a randomized phase 2 trial evaluating the sequence of abiraterone acetate plus prednisone followed by enzalutamide (group A) versus the opposite sequence (group B).31 In this trial, 202 patients were randomly assigned to either group A (n=101) or group B (n=101). Time to second PSA progression was longer in group A than in group B (median 19.3 months versus 15.2 months; HR=0.66; 95% CI 0.45–0.97; p=0.036). PSA responses to second-line therapy were seen in 36% of patients for enzalutamide and 4% for abiraterone acetate. This study suggests that abiraterone acetate plus prednisone followed by enzalutamide would be the favored sequence in mCRPC if both agents were used. 31. 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. (Conditional Recommendation; Evidence Level: Grade B) 32. 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. (Strong Recommendation; Evidence Level: Grade B) Cabazitaxel was approved as second-line chemotherapy in 2010 based on the results of the TROPIC trial.14 TROPIC randomized 755 men with mCRPC who had previously received docetaxel chemotherapy and demonstrated median survival of 15.1 months in the cabazitaxel group and 12.7 months in the mitoxantrone group. The HR for death of men treated with cabazitaxel compared with those taking mitoxantrone was 0.70 (95% CI 0.59–0.83; p <0.0001). Abiraterone acetate and enzalutamide were not available at the time of the TROPIC trial, so it is unknown if this would have influenced the positive outcomes seen in TROPIC. Optimal third line therapy for mCRPC is unknown. The majority of patients will receive one ART with abiraterone acetate plus prednisone or enzalutamide and docetaxel chemotherapy. The CARD trial32 tested the efficacy and safety of cabazitaxel versus the alternative ART therapy in patients with mCRPC who progressed after two prior therapies. A total of 255 patients were randomized, and progression or death was reported in 73.6% in the cabazitaxel group compared with 80.2% in the group that received a second ART (HR=0.54; 95% CI 0.40–0.73; p 50% decline in PSA.35 In May 2017, the FDA approved pembrolizumab for patients with any metastatic, microsatellite instability-high or mismatch repair deficient histology who have progressed following prior treatment and who have no satisfactory alternative treatment options.36 Bone Health Several factors conspire to place the average patient with metastatic prostate cancer at a higher risk of bone complications. First, the median age of onset of the disease is in the late 60s, meaning that the average patient with metastatic disease may be in his 70s (or beyond), clearly a population at risk of physiologic, age-related decreases in bone mineral density. Secondly, a primary therapeutic intervention in patients with recurrent disease (ie, ADT) is associated with progressive loss of bone mineral density, not infrequently to the point of measurable osteopenia or frank osteoporosis, increasing the patient's fracture risk, even in patients with non-metastatic disease.37,38 Finally, in patients with advanced disease, bones are the most common site of metastatic disease, with many patients at some point in their course demonstrating evidence of disease in this site. 35. 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) 36. Clinicians should recommend preventative treatment for fractures and SREs, including supplemental calcium, vitamin D, smoking cessation, and weight-bearing exercise, to advanced prostate cancer patients on ADT. (Clinical Principle) 37. 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) 38. Clinicians should prescribe a bone-protective agent (denosumab or zoledronic acid) for mCRPC patients with bony metastases to prevent SREs. (Moderate Recommendation; Evidence Level: Grade B) Future Directions Several key areas of future research need emphasis to improve clinical care and provide a path to better patient outcomes with advanced prostate cancer. While dramatic recent advances have been made, there are many unmet needs in prostate cancer management. As we move forward as a field, we need to focus on the biologic make-up of tumors and how these can be better leveraged to identify treatment options for patients. Disclaimer: This document was written by the Advanced Prostate Cancer Guideline Panel of the American Urological Association Education and Research, Inc., which was created in 2018. The Practice Guidelines Committee (PGC) of the AUA selected the committee chair. Panel members were selected by the chair. Membership of the Panel included specialists in urology, oncology, and radiation oncology with specific expertise on this disease space. The mission of the panel was to develop recommendations that are analysis based or consensus-based, depending on panel processes and available data, for optimal clinical practices in the treatment of advanced prostate cancer. Funding of the panel was provided by the AUA. Panel members received no remuneration for their work. Each member of the panel provides an ongoing conflict of interest disclosure to the AUA, and the Panel Chair, with the support of AUA Guidelines staff and the PGC, reviews all disclosures and addresses any potential conflicts per AUA’s Principles, Policies and Procedures for Managing Conflicts of Interest. While these guidelines do not necessarily establish the standard of care, AUA seeks to recommend and to encourage compliance by practitioners with current best practices related to the condition being treated. As medical knowledge expands and technology advances, the guidelines will change. Today these evidence-based guidelines statements represent not absolute mandates but provisional proposals for treatment under the specific conditions described in each document. For all these reasons, the guidelines do not pre-empt physician judgment in individual cases. Treating physicians must take into account variations in resources, and patient tolerances, needs, and preferences. Conformance with any clinical guideline does not guarantee a successful outcome. The guideline text may include information or recommendations about certain drug uses (‘off label‘) that are not approved by the Food and Drug Administration (FDA), or about medications or substances not subject to the FDA approval process. AUA urges strict compliance with all government regulations and protocols for prescription and use of these substances. The physician is encouraged to carefully follow all available prescribing information about indications, contraindications, precautions and warnings. These guidelines and best practice statements are not intended to provide legal advice about use and misuse of these substances. Although guidelines are intended to encourage best practices and potentially encompass available technologies with sufficient data as of close of the literature review, they are necessarily time-limited. Guidelines cannot include evaluation of all data on emerging technologies or management, including those that are FDA-approved, which may immediately come to represent accepted clinical practices. For this reason, the AUA does not regard technologies or management which are too new to be addressed by this guideline as necessarily experimental or investigational. References 1. : Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008; 68: 4447. Google Scholar 2. : Activation of the androgen receptor by intratumoral bioconversion of androstanediol to dihydrotestosterone in prostate cancer. Cancer Res 2011; 71: 1486. Google Scholar 3. : Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2018; 378: 2465. Google Scholar 4. : Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018; 378: 1408. Google Scholar 5. : Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2019; 380: 1235. Google Scholar 6. : Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 2012; 379: 39. Google Scholar 7. : Enzalutamid and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2020; 382: 2197. Google Scholar 8. : Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol 2013; 31: 3800. Google Scholar 9. : Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Eng J Med 2004; 351: 1502. Google Scholar 10. : Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004; 351: 1513. Google Scholar 11. : Increased survival with enzalutamide in prostate cancer after chemotherapy. N Eng J Med 2012; 367: 1187. Google Scholar 12. : Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011; 364: 1995. Google Scholar 13. : Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411. Google Scholar 14. : Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial. Lancet 2010; 376: 1147. Google Scholar 15. : Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013; 369: 213. Google Scholar 16. : Predicting time from metastasis to overall survival in castration-resistant prostate cancer: results from SEARCH. Clin Genitourin Cancer 2017; 15: 60. Google Scholar 17. : Time to castration resistance is an independent predictor of castration-resistant prostate cancer survival. Anticancer Res 2011; 31: 1475. Google Scholar 18. : Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int 2017; 120: E80. Google Scholar 19. : Prognostic model predicting metastatic castration-resistant prostate cancer survival in men treated with second-line chemotherapy. J Natl Cancer Inst 2013; 105: 1729. Google Scholar 20. : The prognostic effect of prostate-specific antigen half-life at the first follow-up visit in newly diagnosed metastatic prostate cancer. Urol Oncol 2015; 33: 383. Google Scholar 21. : A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: a TAX327 study analysis. Clin Cancer Res 2007; 13: 6396. Google Scholar 22. : The prognostic importance of metastatic site in men with metastatic castration-resistant prostate cancer. Eur Urol 2014; 65: 3. Google Scholar 23. : Impact of the site of metastases on survival in patients with metastatic prostate cancer. Eur Urol 2015; 68: 325. Google Scholar 24. : Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL. Prostate Cancer Prostatic Dis 2017; 20: 221. Google Scholar 25. : Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med 2016; 375: 443. Google Scholar 26. : PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol 2019; 37: 490. Google Scholar 27. : Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013; 368: 138. Google Scholar 28. : Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2015; 16: 152. Google Scholar 29. : Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014; 371: 424. Google Scholar 30. : Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 2008; 26: 242. Google Scholar 31. : Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol 2019; 20: 1730. Google Scholar 32. : Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med 2019; 381: 2506. Google Scholar 33. : Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 2020; 382: 2091. Google Scholar 34. : The association between germline BRCA2 variants and sensitivity to platinum-based chemotherapy among men with metastatic prostate cancer. Cancer 2017; 123: 3532. Google Scholar 35. : Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade. JAMA Oncol 2019; 5: 471. Google Scholar 36. : FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Ca Res 2019; 25: 3753. Google Scholar 37. : Gonadotropin-releasing hormone agonists and fracture risk; a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol 2005; 23: 7897. Google Scholar 38. : Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 2005; 352: 154. Google Scholar The complete unabridged version of the guideline is available at http://jurology.com/. This document is being printed as submitted independent of editorial or peer review by the editors of The Journal of Urology®. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 205Issue 1January 2021Page: 22-29Supplementary Materials Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.KeywordsProstate cancerantiandrogensMetricsAuthor Information William T. Lowrance,* More articles by this author Rodney H. Breau More articles by this author Roger Chou More articles by this author Brian F. Chapin More articles by this author Tony Crispino More articles by this author Robert Dreicer More articles by this author David F. Jarrard More articles by this author Adam S. Kibel More articles by this author Todd M. Morgan More articles by this author Alicia K. Morgans More articles by this author William K. Oh More articles by this author Matthew J. Resnick More articles by this author Anthony L. Zietman More articles by this author Michael S. Cookson More articles by this author Expand All The complete unabridged version of the guideline is available at http://jurology.com/. This document is being printed as submitted independent of editorial or peer review by the editors of The Journal of Urology®. Advertisement Advertisement PDF DownloadLoading ...
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