Neoadjuvant hormonal therapy before radical prostatectomy in high-risk prostate cancer.

Published on Sep 15, 2021in Nature Reviews Urology14.432
· DOI :10.1038/S41585-021-00514-9
Gaëtan Devos6
Estimated H-index: 6
(Katholieke Universiteit Leuven),
Wout Devlies3
Estimated H-index: 3
(Katholieke Universiteit Leuven)
+ 9 AuthorsWouter Everaerts23
Estimated H-index: 23
(Katholieke Universiteit Leuven)
Sources
Abstract
Patients with high-risk prostate cancer treated with curative intent are at an increased risk of biochemical recurrence, metastatic progression and cancer-related death compared with patients treated for low-risk or intermediate-risk disease. Thus, these patients often need multimodal therapy to achieve complete disease control. Over the past two decades, multiple studies on the use of neoadjuvant treatment have been performed using conventional androgen deprivation therapy, which comprises luteinizing hormone-releasing hormone agonists or antagonists and/or first-line anti-androgens. However, despite results from these studies demonstrating a reduction in positive surgical margins and tumour volume, no benefit has been observed in hard oncological end points, such as cancer-related death. The introduction of potent androgen receptor signalling inhibitors (ARSIs), such as abiraterone, apalutamide, enzalutamide and darolutamide, has led to a renewed interest in using neoadjuvant hormonal treatment in high-risk prostate cancer. The addition of ARSIs to androgen deprivation therapy has demonstrated substantial survival benefits in the metastatic castration-resistant, non-metastatic castration-resistant and metastatic hormone-sensitive settings. Intuitively, a similar survival effect can be expected when applying ARSIs as a neoadjuvant strategy in high-risk prostate cancer. Most studies on neoadjuvant ARSIs use a pathological end point as a surrogate for long-term oncological outcome. However, no consensus yet exists regarding the ideal definition of pathological response following neoadjuvant hormonal therapy and pathologists might encounter difficulties in determining pathological response in hormonally treated prostate specimens. The neoadjuvant setting also provides opportunities to gain insight into resistance mechanisms against neoadjuvant hormonal therapy and, consequently, to guide personalized therapy. Cancer recurrence after radical prostatectomy for high-risk prostate cancer is common. The addition of neoadjuvant hormonal therapy with the introduction of potent androgen receptor signalling inhibitors has gained interest in the oncological community. However, conclusions of a survival benefit with this therapy cannot currently be made and results of several phase II trials are much anticipated.
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References212
Newest
#1Hyuna Sung (ACS: American Cancer Society)H-Index: 19
#2Jacques Ferlay (IARC: International Agency for Research on Cancer)H-Index: 72
Last. Freddie Bray (IARC: International Agency for Research on Cancer)H-Index: 126
view all 7 authors...
This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated ...
Source
#1Jacob E. Berchuck (Harvard University)H-Index: 9
#2Zhenwei Zhang (UMMS: University of Massachusetts Medical School)H-Index: 10
Last. Mary-Ellen Taplin (Harvard University)H-Index: 67
view all 11 authors...
Abstract Background Intense neoadjuvant androgen deprivation therapy (ADT) before radical prostatectomy (RP) is an investigational approach to reduce recurrence rates in men with high-risk localized prostate cancer (PCa). The impact of germline DNA damage repair (gDDR) gene alterations on response to intense neoadjuvant ADT is not known. Objective To evaluate the prevalence of gDDR alterations among men with localized PCa at high risk of recurrence and evaluate their impact on response to intens...
Source
#1Mengxia Chen (NU: Nanjing University)H-Index: 6
#2Junlong Zhuang (NU: Nanjing University)H-Index: 11
Last. Hongqian Guo (NU: Nanjing University)H-Index: 24
view all 9 authors...
Purpose:We explored the role of 68Ga-PSMA-11 positron emission/computerized tomography as a predictor of pathological response to neoadjuvant androgen deprivation therapy combined with abiraterone ...
Source
#1Scott WilkinsonH-Index: 7
#2Huihui Ye (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 28
Last. Nicole V. CarrabbaH-Index: 5
view all 28 authors...
Abstract Background Patients diagnosed with high risk localized prostate cancer have variable outcomes following surgery. Trials of intense neoadjuvant androgen deprivation therapy (NADT) have shown lower rates of recurrence among patients with minimal residual disease after treatment. The molecular features that distinguish exceptional responders from poor responders are not known. Objective To identify genomic and histologic features associated with treatment resistance at baseline. Design, se...
Source
#1Laura S. Graham (UW: University of Washington)H-Index: 2
#2Lawrence D. True (UW: University of Washington)H-Index: 82
Last. Michael T. Schweizer (UW: University of Washington)H-Index: 27
view all 21 authors...
Background Localized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP). Methods This was an open label, si...
Source
#1Rana R. McKay (UCSD: University of California, San Diego)H-Index: 31
#2Wanling Xie (Harvard University)H-Index: 52
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Purpose:This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy (RP) pathologic response and radiographic and tissue biomarkers in...
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#1Laila A. Gharzai (UM: University of Michigan)H-Index: 6
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Summary Background The international Intermediate Clinical Endpoints in Cancer of the Prostate working group has established metastasis-free survival as a surrogate for overall survival in localised prostate cancer based on the findings of 19 predominantly radiotherapy-based trials. We sought to comprehensively assess aggregate trial-level performance of commonly reported intermediate clinical endpoints across all randomised trials in localised prostate cancer. Methods For this meta-analysis, we...
Source
#1Nicolas MottetH-Index: 39
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Abstract Objective To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa). Evidence acquisition The panel performed a literature review of new data, covering the tim...
Source
#1Rana R. McKay (UCSD: University of California, San Diego)H-Index: 31
#2Jacob E. Berchuck (Harvard University)H-Index: 9
Last. Mary-Ellen Taplin (Harvard University)H-Index: 67
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Purpose:We report on the post-radical prostatectomy (RP) outcomes of patients enrolled on three randomized, multicenter, clinical trials of intense neoadjuvant androgen deprivation therapy (ADT) th...
Source
#1Fatima KarzaiH-Index: 13
Last. William L. DahutH-Index: 64
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Purpose: For high-risk prostate cancer, standard treatment options include radical prostatectomy (RP) or radiotherapy plus androgen deprivation therapy (ADT). Despite definitive therapy, many patients will have disease recurrence. Imaging has the potential to better define characteristics of response and resistance. In this study, we evaluated prostate multiparametric MRI (mpMRI) before and after neoadjuvant enzalutamide plus ADT. Patients and Methods: Men with localized intermediate- or high-ri...
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Neoadjuvant intense androgen deprivation therapy can exert a wide range of histologic responses, which in turn are reflected in the final prostatectomy specimen. Accurate identification and measurement of residual tumor volumes are critical for tracking and stratifying patient outcomes. The goal of this current study was to evaluate the ability of antibodies against prostate-specific membrane antigen (PSMA) to detect residual tumor in a cohort of 35 patients treated with androgen deprivation the...
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