Should androgen deprivation therapy and other systemic treatments be used in men with prostate cancer and a rising PSA post-local treatments?

Patrikidou, Anna; Zilli, Thomas; Baciarello, Giulia; Terisse, Safae; Hamilou, Zineb; Fizazi, Karim

doi:10.1177/17588359211051870

Cited by 4 publications

(2 citation statements)

References 129 publications

(203 reference statements)

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“…Males who have a PSA nadir of less than 0.01 ng/mL have a high (96%) chance of not having a relapse within two years. Furthermore, clinical features such as ISUP grade and surgical margin status combined with a post-RP PSA levels > 0.01 ng/mL are able to predict BCR and are helpful in determining follow-up intervals [4]. A PSA increase >2 ng/mL higher than the PSA nadir value, regardless of the serum concentration of the nadir, is the RTOG-ASTRO Phoenix Consensus Conference definition of PSA failure following primary RT [5].…”

Section: Definition and Incidencementioning

confidence: 99%

How the Management of Biochemical Recurrence in Prostate Cancer Will Be Modified by the Concept of Anticipation and Incrementation of Therapy

Sciarra,

Santarelli,

Salciccia

et al. 2024

Cancers

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Biochemical recurrence (BCR) after primary treatments for prostate cancer (PC) is an extremely heterogeneous phase and at least a stratification into low- and high-risk cases for early progression in metastatic disease is necessary. At present, PSA-DT represents the best parameter to define low- and high-risk BCR PC, but real precision medicine is strongly suggested to define tailored management for patients with BCR. Before defining management, it is necessary to exclude the presence of low-volume metastasis associated with PSA progression using new-generation imaging, preferably with PSMA PET/CT. Low-risk BCR cases should be actively observed without early systemic therapies. Early treatment of low-risk BCR with continuous androgen deprivation therapy (ADT) can produce disadvantages such as the development of castration resistance before the appearance of metastases (non-metastatic castration-resistant PC). Patients with high-risk BCR benefit from early systemic therapy. Even with overall survival (OS) as the primary treatment endpoint, metastasis-free survival (MFS) should be used as a surrogate endpoint in clinical trials, especially in long survival stages of the disease. The EMBARK study has greatly influenced the management of high-risk BCR, by introducing the concept of anticipation and intensification through the use of androgen receptor signaling inhibitors (ARSIs) and ADT combination therapy. In high-risk (PSA-DT ≤ 9 months) BCR cases, the combination of enzalutamide with leuprolide significantly improves MFS when compared to leuprolide alone, maintaining an unchanged quality of life in the asymptomatic phase of the disease. The possibility of using ARSIs alone in this early disease setting is suggested by the EMBARK study (arm with enzalutamide alone) with less evidence than with the intensification of the combination therapy. Continued use versus discontinuation of enzalutamide plus leuprolide intensified therapy upon reaching undetectable PSA levels needs to be better defined with further analysis. Real-world analysis must verify the significant results obtained in the context of a phase 3 study.

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Section: Definition and Incidencementioning

confidence: 99%

How the Management of Biochemical Recurrence in Prostate Cancer Will Be Modified by the Concept of Anticipation and Incrementation of Therapy

Sciarra,

Santarelli,

Salciccia

et al. 2024

Cancers

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“…Nodal oligorecurrent prostate cancer (PCa) is an emerging disease status generated by the widespread use of molecular imaging to restage biochemical relapse after curative treatment [1][2][3][4][5]. Systemic therapy with androgen deprivation therapy (ADT) remains the standard treatment of these patients [6]. Due to the limited metastatic burden and a good long-term survival [7,8], metastasis directed therapies (MDT) have been proposed as a therapeutic alternative to improve progression-free survival or postpone use of systemic therapies [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Oligorecurrent nodal prostate cancer: Radiotherapy quality assurance of the randomized PEACE V-STORM phase II trial

Achard

Jaccard

Vanhoutte

et al. 2022

Radiotherapy and Oncology

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How the Management of Biochemical Recurrence in Prostate Cancer Will be Modified by the Concept of Anticipation and Incrementation of Therapy

Sciarra,

Santarelli,

Salciccia

et al. 2024

Preprint

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Biochemical recurrence (BCR) after primary treatments for prostate cancer (PC) is an extremely heterogeneous phase and at least a stratification in low and high-risk cases for early progression in metastatic disease is necessary. At now PSA-DT represents the best parameter to define low and high risk BCR PC, but a real precision medicine is strongly suggested to define a tailored management of patients with BCR. Before defining management, it is necessary to exclude the presence of low volume metastasis associated with PSA progression using new generation imaging preferably with PSMA PET/CT. Low risk BCR cases should be actively observed without early systemic therapies. Early treatment of low risk BCR with continuous androgen deprivation therapy (ADT) can produce disadvantages such the development of castration resistance before the appearance of metastases (non-metastatic castration resistant PC). Patients with high risk BCR benefit from early systemic therapy. The primary end point must be metastasis-free survival (MFS), even with the same overall survival (OS). The EMBARK study is able to impact on the management of high risk BCR, by introducing the concept of anticipation and intensification through the use of androgen receptor signaling inhibitors (ARSI) and ADT combination therapy. In high risk (PSA-DT ≤ 9 months) BCR cases, the combination of enzalutamide with leuprolide significantly improves MFS when compared to leuprolide alone, maintaining the quality of life unchanged in an asymptomatic phase of the disease. The possibility of using ARSI alone in this early disease setting is suggested by the EMBARK study (arm with enzalutamide alone) with less evidence than the intensification of the combination therapy. Continued use versus discontinuation upon reaching undetectable PSA levels of enzalutamide plus leuprolide intensified therapy needs to be better defined with further analysis. Real world analysis must verify the significant results obtained in the context of a phase 3 study.

show abstract

Should androgen deprivation therapy and other systemic treatments be used in men with prostate cancer and a rising PSA post-local treatments?

Cited by 4 publications

References 129 publications

How the Management of Biochemical Recurrence in Prostate Cancer Will Be Modified by the Concept of Anticipation and Incrementation of Therapy

How the Management of Biochemical Recurrence in Prostate Cancer Will Be Modified by the Concept of Anticipation and Incrementation of Therapy

Oligorecurrent nodal prostate cancer: Radiotherapy quality assurance of the randomized PEACE V-STORM phase II trial

How the Management of Biochemical Recurrence in Prostate Cancer Will be Modified by the Concept of Anticipation and Incrementation of Therapy

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