Resolution of the Expert Council on the New Approach to Drug Therapy for Non-Metastatic Castration-Resistant Prostate Cancer

Relevance: Prostate cancer (PC) is one of the most common malignant neoplasms in the male population. The widespread introduction of modern diagnostic methods and the determination of prostate-specific antigen (PSA) levels have increased the number of detected cases of localized and locally advanced PC forms. However, in some patients treated with radical methods and long-term androgen deprivation therapy (ADT), the disease continues to progress in the form of an increase in PSA levels with castration testosterone values and with no distant metastases. Such a course of the disease is referred to as non-metastatic castration-resistant prostate cancer (nmCRPC). Purpose: The article reports the results of a meeting of the Expert Council arranged by the Kazakh Research Institute of Oncology and Radiology on December 25, 2020, on non-metastatic castration-resistant prostate cancer diagnostics and treatment. Results: Large clinical studies highlight the critical importance of controlling the PSA doubling time as the main prognostic factor for an unfavorable outcome to increase patient survival and prevent the development of distant metastases. Based on the results of large randomized studies, experts recommended using new-generation androgen receptor antagonists in combination with ongoing ADT to improve the clinical outcomes in nmCRPC patients at high risk of metastatic progression. The Expert Council was presented with the data of a registration clinical study on darolutamide efficacy and safety. The advantages of introducing this drug into clinical practice to expand the choice of therapeutic options were identified. Personalized adjustment of a treatment regimen will increase the treatment efficacy and ensure higher survival in this category of patients. Conclusion: Increasing survival as the main objective in treating nmCRPC patients requires improved diagnostics through regular controlling of testosterone and PSA levels, calculation of PSA doubling time, and the use of radiological diagnostic methods to rule out distant metastases. The choice of therapy in patients at high risk of metastasis shall consider the patient’s status and the treatment efficacy and safety balance.

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Resolution of the Expert Council on the new approach to drug therapy for non-metastatic castration-resistant prostate cancer

Oncologia i radiologia Kazakhstana ◽

10.52532/2663-4864-2021-1-59-8-11 ◽

2021 ◽

Vol 59 (1) ◽

pp. 8-11

Author(s):

Dilyara Kaidarova ◽

Oxana Shatkovskaya ◽

Zaure Dushimova ◽

Bakytzhan Ongarbayev

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Treatment Efficacy ◽

Doubling Time ◽

Distant Metastases ◽

Diagnostic Methods ◽

Efficacy And Safety ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Psa Doubling Time

Prostate cancer (PC) is one of the most common malignant neoplasms in the male population. The widespread introduction of modern diagnostic methods and the determination of prostate-specific antigen (PSA) levels have increased the number of detected cases of localized and locally advanced PC forms. However, in some patients treated with radical methods and long-term androgen deprivation therapy (ADT), the disease continues to progress in the form of an increase in PSA levels with castration testosterone values and with no distant metastases. Such a course of the disease is referred to as non-metastatic castration-resistant prostate cancer (nmCRPC). Purpose: The article reports the results of a meeting of the Expert Council arranged by the Kazakh Research Institute of Oncology and Radiology on December 25, 2020, on non-metastatic castration-resistant prostate cancer diagnostics and treatment. Results: Large clinical studies highlight the critical importance of controlling the PSA doubling time as the main prognostic factor for an unfavorable outcome to increase patient survival and prevent the development of distant metastases. Based on the results of large randomized studies, experts recommended using new-generation androgen receptor antagonists in combination with ongoing ADT to improve the clinical outcomes in nmCRPC patients at high risk of metastatic progression. The Expert Council was presented with the data of a registration clinical study on darolutamide efficacy and safety. The advantages of introducing this drug into clinical practice to expand the choice of therapeutic options were identified. Personalized adjustment of a treatment regimen will increase the treatment efficacy and ensure higher survival in this category of patients. Conclusion: Increasing survival as the main objective in treating nmCRPC patients requires improved diagnostics through regular controlling of testosterone and PSA levels, calculation of PSA doubling time, and the use of radiological diagnostic methods to rule out distant metastases. The choice of therapy in patients at high risk of metastasis shall consider the patient’s status and the treatment efficacy and safety balance.

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Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-018-0095-0 ◽

2018 ◽

Vol 22 (2) ◽

pp. 252-260 ◽

Cited By ~ 6

Author(s):

Colette A. Whitney ◽

Lauren E. Howard ◽

Stephen J. Freedland ◽

Amanda M. DeHoedt ◽

Christopher L. Amling ◽

...

Keyword(s):

Prostate Cancer ◽

Competing Risks ◽

Doubling Time ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Psa Doubling Time

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Current opportunities of therapy for patients with non-metastatic castration-resistant prostate cancer

Cancer Urology ◽

10.17650/1726-9776-2020-16-3-190-197 ◽

2020 ◽

Vol 16 (3) ◽

pp. 190-197

Author(s):

B. Ya. Alekseev ◽

K. M. Nushko ◽

P. S. Kozlova ◽

A. D. Kaprin ◽

O. I. Mailyan

Keyword(s):

Prostate Cancer ◽

Locally Advanced ◽

Specific Antigen ◽

Distant Metastases ◽

Diagnostic Methods ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Psa Testing ◽

Urological Malignancies ◽

And Control

Prostate cancer is one of the most common urological malignancies. Improved diagnostic methods and widespread implementation of mandatory prostate specific antigen (PSA) testing in a number of clinics have led to an increase in the number of timely diagnosed cases of localized and locally advanced prostate cancer, as well as to the expansion of indications for radical therapies. Nevertheless, 30 % to 50 % of patients (depending on their risk) develop biochemical relapse after surgery or radiotherapy. Non-metastatic castration-resistant prostate cancer is usually a result of disease progression after radical treatment and long-term androgen-deprivation therapy, which manifests by constant increase in the PSA level along with castrate level of testosterone and no distant metastases according to the results of comprehensive radiological examination. A number of large clinical studies have demonstrated that regular examinations and control of PSA doubling time (main prognostic factor associated with poor disease outcome) are crucial to increase survival and prevent the development of distant metastases.This paper aims to provide an overview of existing literature on the problems associated with diagnosis and treatment of non-metastatic castration-resistant prostate cancer. We have analyzed large randomized studies that demonstrated an increase in the overall survival of patients receiving selective androgen receptor antagonists.

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ARAMIS trial: Efficacy and safety phase 3 trial of ODM-201 in men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.tps5080 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. TPS5080-TPS5080

Author(s):

Karim Fizazi ◽

Neal D. Shore ◽

Teuvo L. J. Tammela ◽

Toni Sarapohja ◽

Annamari Vuorela ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Efficacy And Safety ◽

Castration Resistant Prostate Cancer ◽

Phase 3 ◽

Castration Resistant

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Efficacy of androgen receptor antagonists in combination with androgen deprivation therapy in nonmetastatic, castration-resistant prostate cancer: A systematic review and meta-analysis of published phase III randomized controlled trials.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17606 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17606-e17606

Author(s):

Nusrat Jahan ◽

Shabnam Rehman ◽

Francis Mogollon-Duffo ◽

Somedeb Ball ◽

Sariya Wongsaengsak ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Doubling Time ◽

Meta Analysis ◽

Final Analysis ◽

Castration Resistant Prostate Cancer ◽

Phase 3 ◽

Free Survival ◽

Castration Resistant ◽

Psa Doubling Time

e17606 Background: Nonmetastatic, castration-resistant prostate cancer (nmCRPC) often heralds metastatic disease which is responsible for majority of the morbidity and mortality associated with prostate cancer. Hence, delaying metastasis is an expedient therapeutic goal for the patients with nmCRPC. Three androgen receptor (AR) antagonists — apalutamide, enzalutamide, and darolutamide — have been approved recently for nmCRPC on the basis of prolongation of metastasis-free survival. The purpose of our meta-analysis is to consolidate the efficacy data of AR-antagonists prolonging metastasis-free survival in nmCRPC. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until November 2019. Phase 3 RCTs using AR-antagonists for nmCRPC were included in the final analysis. We used generic inverse variance method and random effects model to calculate the pooled hazard ratio (HR) for distant metastasis or death with 95% confidence interval (CI). Heterogeneity was tested with I2 value and Cochran’s Q test. Results: Three phase 3 RCTs (ARAMIS, PROSPER, and SPARTAN) randomizing 2694 patients in the AR-antagonist arms and 1423 patients in the control arms are included in the final analysis. All studies enrolled only patients with prostate specific antigen (PSA) doubling time of 10 months or less. AR-antagonists used in the study arms were — ARAMIS: darolutamide, PROSPER: enzalutamide, and SPARTAN: apalutamide. Placebo was used in the control arms. All patients continued androgen deprivation therapy (ADT). Randomization was 2:1 in all studies. The pooled HR for distant metastasis or death was highly significant at 0.32 (95% CI: 0.25 - 0.41; P < 0.00001, I2 = 79%) in the favor of AR-antagonist arm in overall population. The pooled HR remained significant when patients were stratified according to PSA doubling time. For patients with PSA doubling time > 6months, the pooled HR was 0.34 (95% CI: 0.27 - 0.43; P < 0.00001, I2 = 0%); for patients with PSA doubling time ≤6 months, the pooled HR was 0.32 (95% CI: 0.25 - 0.41; P < 0.00001, I2 = 73%). Conclusions: Our meta-analysis demonstrated addition of AR-antagonists to ADT significantly prolongs the metastasis-free survival in patients with nmCRPC — an exciting new development in the management of prostate cancer.

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