Earlier use of androgen receptor‐axis‐targeted drugs may improve overall survival in patients with non‐metastatic castration‐resistant prostate cancer

Mori, Keiichiro; Kimura, Takahiro; Ito, Ken; Onuma, Hajime; Tanaka, Masatoshi; Matsuura, Taishi; Kurokawa, Gaku; Iwatani, Kosuke; Inaba, Yuzo; Sakanaka, Keigo; Sasaki, Hiroshi; Miki, Jun; Shimomura, Takeshi; Miki, Kenta; Egawa, Shin

doi:10.1002/pros.23534

Cited by 12 publications

(6 citation statements)

References 19 publications

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“…The prognosis of CRPC patients with lymph node metastases is poor, the median OS of which is estimated only 31.6 months (8). Apalutamide and enzalutamide are preferred to treat nmCRPC for the encouraging results from the PROSPER trial and the SPARTAN trial, and earlier use of androgen receptor-axis-targeted drugs (ARAT) may improve OS, PFS, and PSA response (9). However, the PROSPER trial does not clarify the nodal status of the patients enrolled, while the SPARTAN trial excludes patients with lymph nodes more than 2 cm.…”

Section: Discussionmentioning

confidence: 99%

Successful management of prostate cancer with bulky pelvic lymph node metastases after rapid development of castration-resistant prostate cancer: a case report with review of the literature

Mai

Yang

et al. 2020

Transl Androl Urol

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The rapid development of castration-resistant prostate cancer (CRPC) is a poor prognostic sign for loco-regionally advanced prostate cancer. Non-metastatic CRPC (nmCRPC) with bulky regional lymph node metastases is extremely rare and difficult to treat clinically without reported case. We present a case of a 72-year-old man with locally advanced prostate cancer with bulky lymph node metastases (53 mm × 77 mm × 67 mm), developing nmCRPC after 9-month ADT treatment. Immunohistochemistry (IHC) tests found partially positive MUC1 and negative BRCA1 expression in the initial biopsy specimens. Nextgeneration sequence analysis on the blood specimen after CRPC predicted a good tolerance to docetaxel.According to the multidisciplinary team recommendations, he was administrated docetaxel 75 mg/m 2 on day 1 every 21 days for 6 cycles, and subsequently radiotherapy, with the delivery of a total dose of 67.5, 60-65 and 47.5 Gy in 25 fractions to the prostate, the enlarged lymph nodes and the whole pelvis respectively. Over a follow-up of 50 months, his disease has achieved good local control and he is alive without evidence of distant metastases or late adverse events. This case highlights individualized and multimodal therapy of intensification of systemic therapy and timely application of radiotherapy in such rare condition.

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Section: Discussionmentioning

confidence: 99%

Successful management of prostate cancer with bulky pelvic lymph node metastases after rapid development of castration-resistant prostate cancer: a case report with review of the literature

Mai

Yang

et al. 2020

Transl Androl Urol

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“…Currently there is one retrospective analysis showing an OS benefit of early use of ARAT in nmCRPC vs mCRPC. The study demonstrated better OS from the time of diagnosis of CRPC in Kaplan-Meier analysis (median OS of 86 months vs 40 months; p = 0.004), with significant improvement observed for PFS ( p =0.048) and PSA response ( p =0.0014) [42]. Multivariate analysis demonstrated nonmetastatic status, low PSA, and long PSA doubling time at ARAT initiation as significant predictors of longer OS ( p =0.044, 0.0001, and 0.026, respectively) [42].…”

Section: Discussionmentioning

confidence: 99%

“…The study demonstrated better OS from the time of diagnosis of CRPC in Kaplan-Meier analysis (median OS of 86 months vs 40 months; p = 0.004), with significant improvement observed for PFS ( p =0.048) and PSA response ( p =0.0014) [42]. Multivariate analysis demonstrated nonmetastatic status, low PSA, and long PSA doubling time at ARAT initiation as significant predictors of longer OS ( p =0.044, 0.0001, and 0.026, respectively) [42]. However, the study had a low number of patients, imbalance in imaging schedules between the two groups, and patients in the mCRPC group had higher-risk features.…”

Section: Discussionmentioning

confidence: 99%

Therapy of Advanced Prostate Cancer: Targeting the Androgen Receptor Axis in Earlier Lines of Treatment

Shah

Vaishampayan

2018

Targ Oncol

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With the decrease in PSA screening based on the 2011 United States Preventive Services Task Force guidelines and the potential approval of highly sensitive imaging techniques over the next few years, we are likely to see an increasing trend of metastatic prostate cancer diagnosis. Traditional therapy for nonmetastatic prostate cancer (nmPC) has consisted of androgen deprivation therapy (ADT) followed by other hormonal therapy maneuvers, such as anti-androgen withdrawal, herbal preparations, low dose steroids, or ketoconazole. Androgen receptor-axis-targeted therapies (ARAT) were previously only approved for patients with metastatic castration resistant prostate cancer (mCRPC). This has recently changed after reporting of results from the SPARTAN and PROSPER trials, which were conducted in nonmetastatic CRPC (nmCRPC) patients. These studies demonstrated improved metastasis-free survival with apalutamide and enzalutamide, each compared to placebo in a double blind randomized setting. In 2017, the LATITUDE and STAMPEDE studies demonstrated marked survival benefit with early abiraterone and prednisone in patients with metastatic hormone sensitive prostate cancer (mHSPC) in addition to ADT. Other second-generation AR antagonists are currently in phase 3 trials in mHSPC and nmCRPC. This article summarizes the key clinical trials that led to FDA approval of ARAT in the mHSPC and nmCRPC settings and highlights potential limitations, future directions, and treatment-algorithms when selecting patients for early therapy in mHSPC and NMPC.

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“…New androgen receptor-axis-targeted agents (ARAT) have improved the prognosis of men with CRPC patients. Although ARAT improves survival in CRPC patients, 2 they remain incurable and eventually progress. A new approach to hormonal therapy is necessary.…”

Section: Introductionmentioning

confidence: 99%

Clinical response in metastatic castration‐resistant prostate cancer (mCRPC) cases treated with supra‐physiological doses of testosterone: Bipolar androgen therapy

Hoshi¹,

Bilim

Hoshi³

et al. 2022

Clinical Case Reports

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Earlier use of androgen receptor‐axis‐targeted drugs may improve overall survival in patients with non‐metastatic castration‐resistant prostate cancer

Abstract: Early use of ARAT may improve OS, PFS, and PSA response in CRPC. Larger, prospective studies will be required to confirm our findings.

Cited by 12 publications

References 19 publications

Successful management of prostate cancer with bulky pelvic lymph node metastases after rapid development of castration-resistant prostate cancer: a case report with review of the literature

Successful management of prostate cancer with bulky pelvic lymph node metastases after rapid development of castration-resistant prostate cancer: a case report with review of the literature

Therapy of Advanced Prostate Cancer: Targeting the Androgen Receptor Axis in Earlier Lines of Treatment

Clinical response in metastatic castration‐resistant prostate cancer (mCRPC) cases treated with supra‐physiological doses of testosterone: Bipolar androgen therapy

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