scholarly journals High Serum Alkaline Phosphatase Flare after First-Line Androgen Deprivation Therapy Predicts Poor Prognosis in Metastatic Prostate Cancer Patients Treated with Second-Generation Androgen Receptor Targeted Therapy

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Satoko Kojima ◽  
Hiroshi Masuda ◽  
Takahito Suyama ◽  
Kyokushin Hou ◽  
Kousuke Mikami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alkaline Phosphatase ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Prognostic Factor ◽  
Metastatic Prostate Cancer ◽  
Second Generation ◽  
Significant Prognostic Factor ◽  
First Line ◽  
Psa Response

Objectives. To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients. Methods. One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated. Results. The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio ( p = 0.0367 ). However, no difference was seen between a high and low ALP flare ratio ( p = 0.8054 ) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS ( p < 0.0001 ). Conclusions. A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision.

scholarly journals Size of pelvic bone metastasis as a significant prognostic factor for metastatic prostate cancer patients

2020 ◽  
Vol 38 (10) ◽  
pp. 993-996
Author(s):  
Toyokazu Hayakawa ◽  
Ken-ichi Tabata ◽  
Hideyasu Tsumura ◽  
Shogo Kawakami ◽  
Takeo Katakura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Metastatic Prostate Cancer ◽  
Pelvic Bone ◽  
Significant Prognostic Factor

Phase II trial of nab-paclitaxel as first-line therapy of hormone refractory metastatic prostate cancer (HRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5152-5152
Author(s):  
T. Kolevska ◽  
C. J. Ryan ◽  
V. Huey ◽  
L. Weisberg ◽  
S. Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Hematologic Toxicity ◽  
Hormone Refractory Prostate Cancer ◽  
First Line ◽  
Psa Response ◽  
Hormone Refractory ◽  
Grade 3

5152 Background: Many patients with hormone refractory prostate cancer have poor tolerance to treatment. Docetaxel chemotherapy was shown to improve survival but has substantial toxicity, requires steroid administration, may cause poorly reversible neuropathy and requires long infusion times, all limiting its use. Nab-paclitaxel, an albumin-bound nanopaticle form of paclitaxel, delivers paclitaxel without steroids, requires only 30 minutes infusion time and has favorable toxicity profile that may be more tolerable but effective in patients with prostate cancer. The goal of this study was to evaluate the efficacy and toxicity of nab-paclitaxel in first line chemotherapy of men with castration resistant prostate cancer. Methods: nab-paclitaxel was given iv100 mg/m2 weekly x 3 of 4 weeks cycles. Main eligibility criteria include: hormone refractory metastatic prostate cancer, no prior chemotherapy, performance status 0–2. Primary endpoint was efficacy based on prostate-specific antigen (PSA) response. PSA response was PSA decrease of >50%, progressive disease (PD) was PSA increase of >25%, stable disease (SD) was <25% PSA increase or <50% decrease sustained longer that 8 weeks. Results: There are 38 patients enrolled, 35 were evaluable for response. Median age was 71 years old (range 57–86). One patient discontinued the treatment after 1 infusion due to toxicity (elevated ALT). PSA response was seen in 9 (25%) patients and SD in 15 patients (43%), with an overall response rate of 25% and clinical benefit of 68%. Seven patients received treatment for ≥ 6 months with minimal toxicity (range 6–10 months). Grade 3 related hematologic toxicity was reported in 7 (18%) patients (4 anemia, 4 neutropenia), grade 3 related non-hematologic toxicity was reported in 6 patients (1 hypokalemia, 1 muscle weakness, 2 fatigue, 1 fever, 1 neuropathy, 1 ALT elevation). Conclusions: Nab-paclitaxel has activity in patients with metastatic hormone refractory prostate cancer. This regimen was well tolerated, and may be useful in patients who are not suitable candidates for docetaxel based therapy. [Table: see text]

scholarly journals Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e042953
Author(s):  
Martin John Connor ◽  
Taimur Tariq Shah ◽  
Katarzyna Smigielska ◽  
Emily Day ◽  
Johanna Sukumar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Androgen Receptor ◽  
Randomised Controlled Trial ◽  
Phase Ii ◽  
Metastatic Prostate Cancer ◽  
Controlled Trial ◽  
Pelvic Lymph Node ◽  
Study Results ◽  
Randomised Controlled

IntroductionSurvival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone.MethodsA phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024.Ethics and disseminationApproved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03763253; ISCRTN58401737

scholarly journals Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors

2021 ◽  
Author(s):  
Fred Saad ◽  
Martin Bögemann ◽  
Kazuhiro Suzuki ◽  
Neal Shore
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Second Generation ◽  
Imaging Techniques ◽  
Specific Antigen ◽  
Conventional Imaging ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Consensus Statements

Abstract Background Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit–risk profile of potential treatments is required. Methods In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function. Results and conclusions While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit–risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.

scholarly journals Expression of AR-V7 (Androgen Receptor Variant 7) Protein in Granular Cytoplasmic Structures Is an Independent Prognostic Factor in Prostate Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2639
Author(s):  
Paul König ◽  
Markus Eckstein ◽  
Rudolf Jung ◽  
Amer Abdulrahman ◽  
Juan Guzman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Analysis ◽  
Androgen Receptor ◽  
Prognostic Factor ◽  
Cancer Biology ◽  
Splice Variants ◽  
Independent Prognostic Factor ◽  
Cytoplasmic Granules ◽  
Cox's Regression ◽  
Cytoplasmic Structures

Prostate cancer (PCa) is the second most common cancer, causing morbidity and mortality among men world-wide. The expression of the androgen receptor (AR) and its splice variants is a crucial factor of prostate cancer biology that has not been comprehensively studied in PCa tumors. The aim of this study was to characterize the protein expression of the AR and its splice variant, AR-V7, and their subcellular distributions in PCa by immunohistochemistry and to correlate the results to the clinicopathological data and prognosis. Immunohistochemical staining for AR and AR-V7 was performed on a tissue microarray (TMA) with specimens from 410 PCa patients using an immunoreactive score (IRS) or only the percentage of AR-V7 staining in cytoplasmic granules. Nuclear or cytoplasmic AR staining was not associated with prognosis. AR-V7 staining was only occasionally observed in the nucleus. However, AR-V7 staining in the cytoplasm or in cytoplasmic granules was associated with relapse-free survival (RFS). AR-V7 staining of the cytoplasm was associated with a shorter RFS, whereas AR-V7 staining of cytoplasmic granules was associated with a longer RFS. In a multivariate Cox’s regression analysis, only negative (<5%) AR-V7 staining of cytoplasmic granules remained an independent prognostic factor for RFS (HR = 5.3; p = 0.006). In a further subgroup analysis by multivariate Cox’s regression analysis, AR-V7 was an independent prognostic factor in the following groups: age ≤ 65 (HR = 9.7; p = 0.029), negative CK20 staining (HR = 7.0; p = 0.008), and positive perineural invasion (HR = 3.7; p = 0.034). Altogether, AR-V7 protein in granular cytoplasmic structures is an independent prognostic factor for RFS in PCa patients.

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