Androgen Antagonists

Importance: Prostate cancer is the most common nonskin cancer in men in the US, with an estimated 299 010 new cases and 35 250 deaths in 2024. Prostate cancer is the second most common cancer in men worldwide, with 1 466 680 new cases and 396 792 deaths in 2022.

Observations: The most common type of prostate cancer is adenocarcinoma (≥99%), and the median age at diagnosis is 67 years. More than 50% of prostate cancer risk is attributable to genetic factors; older age and Black race (annual incidence rate, 173.0 cases per 100 000 Black men vs 97.1 cases per 100 000 White men) are also strong risk factors. Recent guidelines encourage shared decision-making for prostate-specific antigen (PSA) screening. At diagnosis, approximately 75% of patients have cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Based on risk stratification that incorporates life expectancy, tumor grade (Gleason score), tumor size, and PSA level, one-third of patients with localized prostate cancer are appropriate for active surveillance with serial PSA measurements, prostate biopsies, or magnetic resonance imaging, and initiation of treatment if the Gleason score or tumor stage increases. For patients with higher-risk disease, radiation therapy or radical prostatectomy are reasonable options; treatment decision-making should include consideration of adverse events and comorbidities. Despite definitive therapy, 2% to 56% of men with localized disease develop distant metastases, depending on tumor risk factors. At presentation, approximately 14% of patients have metastases to regional lymph nodes. An additional 10% of men have distant metastases that are associated with a 5-year survival rate of 37%. Treatment of metastatic prostate cancer primarily relies on androgen deprivation therapy, most commonly through medical castration with gonadotropin-releasing hormone agonists. For patients with newly diagnosed metastatic prostate cancer, the addition of androgen receptor pathway inhibitors (eg, darolutamide, abiraterone) improves survival. Use of abiraterone improved the median overall survival from 36.5 months to 53.3 months (hazard ratio, 0.66 [95% CI, 0.56-0.78]) compared with medical castration alone. Chemotherapy (docetaxel) may be considered, especially for patients with more extensive disease.

Conclusions and relevance: Approximately 1.5 million new cases of prostate cancer are diagnosed annually worldwide. Approximately 75% of patients present with cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Management includes active surveillance, prostatectomy, or radiation therapy, depending on risk of progression. Approximately 10% of patients present with metastatic prostate cancer, which has a 5-year survival rate of 37%. First-line therapies for metastatic prostate cancer include androgen deprivation and novel androgen receptor pathway inhibitors, and chemotherapy for appropriate patients.

Author/s:

Ruben Raychaudhuri, Daniel W Lin, R Bruce Montgomery

Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment

Aubrey Delammermore — Wed, 05 Apr 2023 05:00:00 +0000

Date Added:

April 5, 2023

Journal/Publication:

New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

March 11, 2023

Issue:

Volume:

URL:

Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/EVIDoa2300018

Keywords

Androgens

Prostatectomy

Patient Reported Outcome Measures

MeSH

Evidence of long-term quality of life-relevant outcome after various treatments for localized prostate cancer from an RCT. James W. Mold, MD, MPH

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Long-term patient-reported outcomes are needed to inform treatment decisions for localized prostate cancer.

METHODS
Patient-reported outcomes of 1643 randomly assigned participants in the ProtecT (Prostate Testing for Cancer and Treatment) trial were evaluated to assess the functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring. This article focuses on the outcomes of the randomly assigned participants from 7 to 12 years using mixed effects linear and logistic models.

RESULTS
Response rates exceeded 80% for most measures. Among the randomized groups over 7 to 12 years, generic quality-of-life scores were similar. Among those in the prostatectomy group, urinary leakage requiring pads occurred in 18 to 24% of patients over 7 to 12 years, compared with 9 to 11% in the active monitoring group and 3 to 8% in the radiotherapy group. In the prostatectomy group, 18% reported erections sufficient for intercourse at 7 years, compared with 30% in the active monitoring and 27% in the radiotherapy groups; all converged to low levels of potency by year 12. Nocturia (voiding at least twice per night) occurred in 34% in the prostatectomy group compared with 48% in the radiotherapy group and 47% in the active monitoring group at 12 years. Fecal leakage affected 12% in the radiotherapy group compared with 6% in the other groups by year 12. The active monitoring group experienced gradual age-related declines in sexual and urinary function, avoiding radical treatment effects unless they changed management.

CONCLUSIONS
ProtecT provides robust evidence about continued impacts of treatments in the long term. These data allow patients newly diagnosed with localized prostate cancer and their clinicians to assess the trade-offs between treatment harms and benefits and enable better informed and prudent treatment decisions. (Funded by the UK National Institute for Health and Care Research Health Technology Assessment Programme projects 96/20/06 and 96/20/99; ISRCTN number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)

Author/s:

Donovan, J. L., Hamdy, F. C., Lane, J. A., Young, G. J., Metcalfe, C., Walsh, E. I., Davis, M., Steuart-Feilding, T., Blazeby, J. M., Avery, K. N., Martin, R. M., Bollina, P., Doble, A., Doherty, A., Gillatt, D., Gnanapragasam, V., Hughes, O., Kockelbergh, R., Kynaston, H., Paul, A., Paez, E., Powell, P., Rosariom D. J., Rowe, E., Manson, M., Catto, J. W., Peters, T. J., Wade, J., Turner, E. L., Williams, N. J., Oxley, J., Staffurth, J., Bryant, R. J., Neal, D. E.

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

Rowan Hutchins — Sun, 19 Mar 2023 05:00:00 +0000

Date Added:

March 19, 2023

Journal/Publication:

NEJM

Publisher:

Massachusetts Medical Society

Publication Date:

March 11, 2023

URL:

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2214122

Keywords

PMID (1):

36912538

MeSH

Disease Progression

Prostate-Specific Antigen

prostatectomy

Androgen Antagonists

prostatic neoplasms

This is the best evidence we have to date regarding the benefits of, or lack thereof, of treatment of localized prostate cancer. James W. Mold, MD, MPH

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Background

Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy.
Methods

At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes).
Results

Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P=0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis.
Conclusions

After 15 years of follow-up, prostate cancer–specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297. opens in new tab; ClinicalTrials.gov number, NCT02044172. opens in new tab.)

Author/s:

Hamdy, Freddie, Donovan, Jenny, Lane, Athene, Metcalfe, Chris, Davis, Michael, Turner, Emma, Martin, Richard, Young, Grace, Walsh, Eleanor, Bryant, Bollina, Prasad, Doble, Andrew