scholarly journals Management of Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Recommendations of a Multidisciplinary Panel of Experts from South America

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ray Manneh ◽  
Ricardo Brugés ◽  
Jose Jaime Correa ◽  
Julián Rojas ◽  
Daniel Rojas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
South America ◽  
Imaging Techniques ◽  
High Sensitivity ◽  
Castration Resistant Prostate Cancer ◽  
Appropriate Use ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Clinical Complexity

Most prostate cancer patients who undergo androgen-deprivation therapy or orchiectomy will eventually develop castration-resistant prostate cancer (CRPC), often preceded by a nonmetastatic CRPC state known as M0CRPC. The recent development of second-generation antiandrogens provides clinicians with efficacious and safe treatments for M0CRPC. However, the complexity of these patients, who typically have to deal with underlying comorbidities and polypharmacy, often challenges therapeutic decisions in this setting. The recent development of novel imaging techniques also provides clinicians with tools for detecting metastases with high sensitivity and specificity. However, the lack of evidence on the early detection of metastases and the corresponding impact on therapeutic decisions makes these techniques a double-edged sword that must be managed appropriately. Here, we present the expert view of the rapidly evolving concept of M0CRPC and provide recommendations for the identification of these patients, the appropriate use of the emerging imaging modalities, and patients’ management, particularly considering their clinical complexity and the recent development of next-generation antiandrogens.

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 Oligometastatic Prostate Adenocarcinoma. Clinical-Pathologic Study of a Histologically Under-Recognized Prostate Cancer

2020 ◽  
Vol 10 (4) ◽  
pp. 265 ◽  
Author(s):  
Claudia Manini ◽  
Alba González ◽  
David Büchser ◽  
Jorge García-Olaverri ◽  
Arantza Urresola ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Local Control ◽  
Chromogranin A ◽  
Prostate Adenocarcinoma ◽  
Fisher Exact Test ◽  
Castration Resistant Prostate Cancer ◽  
Ki 67 ◽  
Pgp 9.5 ◽  
Castration Resistant ◽  
Therapeutic Decisions

The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment was achieved in 22 (81.5%) patients. A total of 8 (29.6%) patients developed castration-resistant prostate cancer. Seventeen (63%) patients presented with non-organ confined disease. The Gleason index 8–10 was the most frequently observed (12 cases, 44.4%) combined grade. Positive immunostainings were detected with androgen receptor (100%), PGP 9.5 (74%), ERG (40.7%), chromogranin A (29.6%), and synaptophysin (18.5%) antibodies. The Ki-67 index value > 5% was observed in 15% of the cases. L1CAM immunostaining was negative in all cases. Fisher exact test showed that successful local control of metastases was associated to mild inflammation, organ confined disease, Ki-67 index < 5%, and Gleason index 3 + 3. A castration resistant status was associated with severe inflammation, atrophy, a Gleason index higher than 3 + 3, Ki-67 index ≥ 5%, and positive PGP 9.5, chromogranin A, and synaptophysin immunostainings. In conclusion, oligometastatic prostate adenocarcinoma does not have a specific clinical-pathologic profile. However, some histologic and immunohistochemical parameters of routine use may help with making therapeutic decisions.

scholarly journals New Developments in the Treatment of Castration-Resistant Prostate Cancer

2014 ◽  
Vol 12 (5S) ◽  
pp. 773-776
Author(s):  
Celestia S. Higano
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial Data ◽  
Annual Conference ◽  
Castration Resistant Prostate Cancer ◽  
New Developments ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Clinical Scenarios ◽  
Hormonal Therapies ◽  
The Right

During the past 4 years, a host of new agents have been approved for the treatment of patients with advanced prostate cancer. As a result, selecting the right agent for the right patient at the right time is a clinical challenge. At the NCCN 19th Annual Conference, Dr. Celestia Higano explored the rationale behind such therapeutic decisions and the supporting clinical trial data. She reviewed the different classes of therapeutic agents, from immunotherapy and hormonal therapies to chemotherapy and radioisotopes, and offered suggestions for the clinical scenarios in which they may be used most successfully.

scholarly journals Bone scan use in the management of metastatic castration-resistant prostate cancer: Survey of practice patterns among Canadian radiation oncologists, medical oncologists, and urologists

2020 ◽  
Vol 14 (11) ◽  
Author(s):  
Mahbuba Meem ◽  
Katherine Zukotynski ◽  
Srinivas Raman ◽  
Urban Emmenegger
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Bone Scan ◽  
Imaging Techniques ◽  
Therapeutic Interventions ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Positron Emission ◽  
Psma Pet ◽  
Bone Scans

The use of skeletal scintigraphy with technetium-99 methylene diphosphonate (hereafter referred to as a bone scan) for evaluating response to systemic treatment in men with metastatic castration-resistant prostate cancer (mCRPC) is an evolving paradigm in this era of advancing therapies and imaging techniques. Indeed, the interpretation of bone scans can be challenging, and there is a growing expectation that advanced imaging techniques such as prostate-specific membrane antigen positron emission tomography/computer tomography (PSMA PET/CT) may play a complementary role.1 The Prostate Cancer Working Group (PCWG) has outlined specific criteria to define disease progression with respect to bone scans performed as part of clinical trials.2 However, there is no high-level evidence for the scheduling and interpretation of bone scans during routine therapeutic interventions for mCRPC. Thus, patterns of bone scan use are variable and practice-dependent outside of clinical trials.

scholarly journals Novel Strategies for Treating Castration-Resistant Prostate Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 339
Author(s):  
David Ka-Wai Leung ◽  
Peter Ka-Fung Chiu ◽  
Chi-Fai Ng ◽  
Jeremy Yuen-Chun Teoh
Keyword(s):  
Prostate Cancer ◽  
Metastatic Disease ◽  
Advanced Prostate Cancer ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Management Options ◽  
Castration Resistant

The development of castration resistance is an inevitable pathway for the vast majority of patients with advanced prostate cancer. Recently, there have been significant breakthroughs in the understanding and management options of castration-resistant prostate cancer. Three novel hormonal agents showed survival benefits in non-metastatic patients. As for metastatic disease, there was an even wider range of management options being investigated. This review summarized advances in the management of castration-resistant prostate cancer (CRPC) including emerging data on novel imaging techniques and treatment strategies.

scholarly journals Prognostic Value of High-Sensitivity Modified Glasgow Prognostic Score in Castration-Resistant Prostate Cancer Patients Who Received Docetaxel

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 773
Author(s):  
Keisuke Ando ◽  
Shinichi Sakamoto ◽  
Shinpei Saito ◽  
Maihulan Maimaiti ◽  
Yusuke Imamura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prognostic Score ◽  
Glasgow Prognostic Score ◽  
High Sensitivity ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Modified Glasgow Prognostic Score ◽  
Castration Resistant ◽  
Docetaxel Treatment

The Glasgow prognostic score, a marker of systemic inflammation, is associated with clinical outcomes in different cancers including prostate cancer. However, there is no evidence for the relationship between the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in prostate cancer and its prognosis. This study aimed to investigate the prognostic significance of Hs-mGPS in castration-resistant prostate cancer (CRPC) treated with docetaxel. We retrospectively analyzed clinical datasets from 131 CRPC patients who received docetaxel treatment at Chiba University Hospital and a related hospital. Clinical factors including Hs-mGPS before docetaxel treatment were evaluated according to overall survival. The numbers of patients with Hs-mGPS of 0, 1, and 2 were 88, 30, and 13, respectively. The median prostate-specific antigen (PSA) level was 28.9 ng/mL. The median testosterone level was 13.0 ng/dL. The percentages of bone and visceral metastases were 80.8% and 10.2%, respectively. For overall survival, Hs-mGPS ≥ 1 (hazard ratio of 2.41; p = 0.0048), testosterone ≥ 13.0 ng/dL (hazard ratio of 2.23; p = 0.0117), and PSA ≥ 28.9 ng/mL (hazard ratio of 2.36; p = 0.0097) were significant poor prognostic factors in the multivariate analysis. The results of the two-group analysis showed that a higher Hs-mGPS was associated with high PSA, alkaline phosphatase, and testosterone levels. The median testosterone levels for Hs-mGPS of 0, 1, and 2 were 9.0, 16.5, and 23.0, respectively. Based on the multivariate analysis, we created a combined score with three prognostic factors: Hs-mGPS, testosterone, and PSA. The low-risk group (score of 0–1) showed a significantly longer overall survival compared to the intermediate-risk (score of 2–3) and high-risk (score of 4) groups (p < 0.0001). Our results demonstrated that an elevated Hs-mGPS was an independent prognostic factor in CRPC patients treated with docetaxel therapy. Risk classification based on Hs-mGPS, testosterone, and PSA may be useful in predicting the prognosis of CRPC patients.

Development of a circulating tumor cell-based RNA classifier for patients with castration-resistant prostate cancer: CTC-PCS/PAM50.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17509-e17509
Author(s):  
Pai-Chi Teng ◽  
Yu Jen Jan ◽  
Minhyung Kim ◽  
Jie-Fu Chen ◽  
Junhee Yoon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Clinical Test ◽  
Castration Resistant Prostate Cancer ◽  
Luminal A ◽  
Luminal B ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Blood Specimens

e17509 Background: Genomic profiling has strongly impacted the contemporary understanding of prostate cancer (PCa). Clinical trials are now testing the utility of genomic classifiers such as the PCS (You, Ca Res 2016) and PAM50 (Zhao, JAMA Onc 2017) systems to optimize therapy selection. As contemporary tissue is not always readily available, especially in metastatic, castration-resistant PCa (mCRPC), a blood-based test would be better suited for assessing patients and predicting treatment response. Methods: The CTC-RNA assay combines the Thermoresponsive (TR)-NanoVelcro system with the NanoString nCounter platform. This allows for CTC purification and RNA analysis. Using a novel bioinformatics approach that accounts for differences in background signals between tissue and blood, we reconstructed the PCS and PAM50 panels to recapitulate both classifiers in this blood-based assay. A weighted Z-score and nearest centroid classifier were used to calculate gene expression and to assign PCS and PAM50 subtypes. Performance of the revised signatures and CTC-RNA assay was benchmarked on simulated spiked-blood specimens. An initial clinical test was performed using clinically annotated, banked blood specimens within the Translational Oncology Program Blood and Biospecimen Bank. Results: CTC-RNA profiles of C4-2B AR signaling inhibitor (ARSI)-resistant sublines were compared to parental C4-2B. C4-2B ARSI-resistant cells had significantly higher PCS1 Z scores, PCS1 probability, and basal probability compared to the parental C4-2B cells. Blood samples from 34 mCRPC patients prior to initiation of therapy with ARSIs (abiraterone, enzalutamide, or apalutamide) were then analyzed. Samples were classified as PCS1 (n = 3), PCS2 (n = 20), and PCS3 (n = 11); luminal A (n = 12), luminal B (n = 11), and basal (n = 11). The biochemical progression-free survival (bPFS) on ARSI and overall survival (OS) for PCS1/Basal vs. other are shown in the table. Conclusions: The CTC-RNA assay is capable of generating luminal-basal classifications such as those in the PCS and PAM50 systems. Given early data of these classifiers and their potential to guide therapeutic decisions, this approach may be useful as an alternative to biopsy to facilitate such decisions. Larger prospective studies will be needed to confirm and validate its clinical utility. [Table: see text]

Optimal Management of Prostate Cancer Based on its Natural Clinical History

2018 ◽  
Vol 18 (5) ◽  
pp. 457-467 ◽  
Author(s):  
Gaetano Facchini ◽  
Francesco Perri ◽  
Gabriella Misso ◽  
Carmine D`Aniello ◽  
Giuseppina Della Vittoria Scarpati ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Natural History ◽  
Systemic Disease ◽  
Late Phase ◽  
High Sensitivity ◽  
Clinical History ◽  
Diagnostic Techniques ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Castrate Resistant

Prostate cancer is the most common malignancy in males and, despite a marked improvement in diagnostic techniques, a not small percentage of prostate tumours is still diagnosed in advanced stage. It is now clear that prostate cancer passes through distinct phases during its natural history, starting from an initial phase, in which the disease has a locoregional extent, until a very late phase when it becomes refractory to hormone therapy. It is important to distinguish between local disease, in which tumor may be considered localized in the gland and a systemic disease characterized by high tumor burden and/or dissemination of circulating tumour cells. All the prostate cancers, at first diagnosis, are characterized by high sensitivity to the androgen deprivation therapy (ADT); however, during the natural history, after a variable period, they become castration resistant. In the past, few therapy options were available for castration resistant prostate cancer, while at present much more approaches can be employed, both hormone-based therapies and chemotherapy regimens. Hypercastration agents are defined as drugs capable to target the androgenandrogen receptor axis even in castrate resistant conditions. Abiraterone and enzalutamide are the only two hypercastration agents available for clinical use. Osteoclast targeted agents, such as zoledronic acid and denosumab can always been employed, but their use should be limited to the castrate resistant setting. The optimal understanding of all phases characterizing the natural history of prostate cancer may certainly be useful for the selection of the best therapeutic options in prostate cancer.

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