scholarly journals Clinicopathologic Diagnostic Approach to Aggressive Variant Prostate Cancer

2019 ◽  
Vol 144 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Varsha Manucha ◽  
John Henegan
Keyword(s):  
Prostate Cancer ◽  
English Language ◽  
Treatment Strategies ◽  
Castration Resistant Prostate Cancer ◽  
Ongoing Research ◽  
Castration Resistant ◽  
Current Review ◽  
Pathologic Features ◽  
Neuroendocrine Carcinomas ◽  
Aggressive Variant

Context.— Aggressive variant prostate cancer (AVPCa) develops in a subset of patients with metastatic castration-resistant prostate cancer. The clinical and histologic overlap of AVPCa with other neuroendocrine carcinomas of the prostate has resulted in a lack of consensus on its terminology and treatment. Objective.— To review AVPCa to familiarize pathologists with this entity so they can actively participate in the detection, ongoing research, and evolving management of AVPCa. Data Sources.— The English language literature was reviewed. Conclusions.— The current review summarizes the pathologic features of AVPCa, describes how it has been defined clinically, and discusses how biomarkers may inform treatment strategies in the future.

scholarly journals Neuroendocrine and Aggressive-Variant Prostate Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3792
Author(s):  
Nicholas Spetsieris ◽  
Myrto Boukovala ◽  
Georgios Patsakis ◽  
Ioannis Alafis ◽  
Eleni Efstathiou
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Molecular Characteristics ◽  
Castration Resistant Prostate Cancer ◽  
Ongoing Research ◽  
Platinum Based Chemotherapy ◽  
Hormonal Therapies ◽  
Aggressive Variant

In prostate cancer, neuroendocrine (NE) differentiation may rarely present de novo or more frequently arises following hormonal therapy in patients with castration-resistant prostate cancer (CRPC). Its distinct phenotype is characterized by an aggressive clinical course, lack of responsiveness to hormonal therapies and poor prognosis. Importantly, a subset of CRPC patients exhibits an aggressive-variant disease with very similar clinical and molecular characteristics to small-cell prostate cancer (SCPC) even though tumors do not have NE differentiation. This aggressive-variant prostate cancer (AVPC) also shares the sensitivity of SCPC to platinum-based chemotherapy albeit with short-lived clinical benefit. As optimal treatment strategies for AVPC remain elusive, currently ongoing research efforts aim to enhance our understanding of the biology of this disease entity and improve treatment outcomes for our patients. This review is an overview of our current knowledge on prostate cancer with NE differentiation and AVPC, with a focus on their clinical characteristics and management, including available as well as experimental therapeutic strategies.

scholarly journals Impact of DNA damage repair defects and aggressive variant features on response to carboplatin‐based chemotherapy in metastatic castration‐resistant prostate cancer

2020 ◽  
Vol 148 (2) ◽  
pp. 385-395
Author(s):  
Peter H. J. Slootbeek ◽  
Marleen L. Duizer ◽  
Maarten J. Doelen ◽  
Iris S. H. Kloots ◽  
Malou C. P. Kuppen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Dna Damage Repair ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Damage Repair ◽  
Aggressive Variant

Modern Management of Castration-resistant Prostate Cancer

2013 ◽  
Vol 09 (01) ◽  
pp. 34 ◽  
Author(s):  
Axel Heidenreich ◽  
David Pfister ◽  
Axel Merseburger ◽  
Georg Bartsch ◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Medical Treatment ◽  
Treatment Options ◽  
Treatment Strategies ◽  
New Drugs ◽  
Control Group ◽  
Daily Routine ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223

The approval or clinical evaluation of several new agents – cabazitaxel, enzalutamide, sipuleucel-T, radium-223 and abiraterone acetate – has significantly changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxelbased chemotherapy. All of these agents have resulted in a significant survival benefit compared with their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and the biological aggressiveness of the disease. Furthermore, treatment-associated side effects differ between the various drugs. As new drugs are approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. It is the aim of this article to (1) summarise the data of established treatment options in mCRPC, (2) highlight new developments of medical treatment, (3) provide clinically useful algorithms for the daily routine and to (4) point out future developments of medical treatment.

scholarly journals Understanding Treatment Strategies and Preferences in Nonmetastatic Castration-Resistant Prostate Cancer From the Japanese Physician Perspective

2021 ◽  
pp. 302-310
Author(s):  
Kazuhiro Suzuki ◽  
Vince Grillo ◽  
Yirong Chen ◽  
Shikha Singh ◽  
Dianne Athene Ledesma
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Treatment Strategies ◽  
Patient Characteristics ◽  
Relative Importance ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Treatment Characteristics ◽  
Hypothetical Treatment ◽  
Preference Weights

PURPOSE Sixteen percent (16%) of patients with castration-resistant prostate cancer (CRPC) show no bone metastasis at diagnosis. However, 33% will become metastatic within 2 years. The goal of treatment in patients with nonmetastatic CRPC (nmCRPC), therefore, is to delay symptomatic metastases without undue toxicity. With novel antiandrogen treatments of different strengths and limitations available, physician preferences for nmCRPC treatment in Japan should be understood. METHODS A discrete choice experiment was conducted. Physicians chose between two hypothetical treatments in nmCRPC defined by six attributes: risk of fatigue, falls or fracture, cognitive impairment, hypertension, rashes as side effects of treatment, and extension of time until cancer-related pain occurs. Relative preference weights and relative importance were estimated by hierarchical Bayesian logistic regression. Physicians were also asked to make treatment decisions based on four hypothetical patient profiles to understand the most important factors driving decision making. RESULTS A total of 151 physicians completed the survey. Extension of time until cancer-related pain occurs was the most important attribute (relative importance, 32.3%; CI, 31.3% to 33.3%). Based on summed preference weights across all attributes, preferences for hypothetical treatment profiles I, II, and III were compared. A hypothetical treatment profile with better safety though shorter extension time was preferred (I: mean [standard deviation] = 1.7 [1.6 to 2.1]) over treatment profiles with lower safety but longer extension time (II: −2.7 [−2.8 to −2.6] and III: −0.2 [−0.3 to −0.1]). Treatment characteristics were more important factors for physicians' decision making than patient characteristics in prescribing treatment. CONCLUSION Physicians preferred a treatment with better safety profile, and treatment characteristics were the most important factors for decision making. This might have implications in physicians' decision making for nmCRPC treatment in the future in Japan.

scholarly journals Genomic Resistance Patterns to Second-Generation Androgen Blockade in Paired Tumor Biopsies of Metastatic Castration-Resistant Prostate Cancer

2017 ◽  
pp. 1-11 ◽  
Author(s):  
G. Celine Han ◽  
Justin Hwang ◽  
Stephanie A.M. Wankowicz ◽  
Zhenwei Zhang ◽  
David Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Androgen Deprivation Therapy ◽  
Second Generation ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Line Of Therapy

Purpose Patients with castration-resistant prostate cancer (CRPC) receive second-generation androgen-deprivation therapy, but frequently experience relapse or do not respond. Understanding the genetic mechanisms of resistance will help to identify strategies and biomarkers that are essential for the next line of therapy. Patients and Methods We analyzed whole exomes of patient-matched pre- and post-treatment tumors from patients with CRPC. These patients had received the secondary androgen-deprivation therapy agent, abiraterone, which suppresses androgens to below castration levels, or enzalutamide, which competitively inhibits the key androgen signaling effector, androgen receptor. Results We observed that abiraterone-resistant tumors harbored alterations in AR and MYC, whereas enzalutamide-resistant tumors gained alterations in cell-cycle pathway genes, such as mutation in cyclin-dependent kinase N2A ( CDKN2A) or amplification of CDK6. Experimentally, overexpressing cell-cycle kinases promoted enzalutamide resistance in androgen-sensitive LnCAP cells that was mitigated via CDK4/6 blockade—palbociclib and ribociclib. Conclusion CDK4/6-mediated resistance observed in preclinical experiments suggests that CDK4/6 amplifications may sufficiently promote enzalutamide resistance in CRPC, and that these patients may respond to palbociclib or ribociclib. The overall observations suggest that, in genomically selected advanced CRPC, clinical strategies against abiraterone- or enzalutamide-resistant tumors may require treatment strategies that are tailored to the resistance mechanisms that are specific to those patient subpopulations.

scholarly journals Enzalutamide therapy for advanced prostate cancer: efficacy, resistance and beyond

2019 ◽  
Vol 26 (1) ◽  
pp. R31-R52 ◽  
Author(s):  
Simon Linder ◽  
Henk G van der Poel ◽  
Andries M Bergman ◽  
Wilbert Zwart ◽  
Stefan Prekovic
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Advanced Prostate Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Castration Resistant ◽  
Novel Drugs

The androgen receptor drives the growth of metastatic castration-resistant prostate cancer. This has led to the development of multiple novel drugs targeting this hormone-regulated transcription factor, such as enzalutamide – a potent androgen receptor antagonist. Despite the plethora of possible treatment options, the absolute survival benefit of each treatment separately is limited to a few months. Therefore, current research efforts are directed to determine the optimal sequence of therapies, discover novel drugs effective in metastatic castration-resistant prostate cancer and define patient subpopulations that ultimately benefit from these treatments. Molecular studies provide evidence on which pathways mediate treatment resistance and may lead to improved treatment for metastatic castration-resistant prostate cancer. This review provides, firstly a concise overview of the clinical development, use and effectiveness of enzalutamide in the treatment of advanced prostate cancer, secondly it describes translational research addressing enzalutamide response vs resistance and lastly highlights novel potential treatment strategies in the enzalutamide-resistant setting.

Therapy Management of Metastatic Prostate Carcinoma in General Practice

2019 ◽  
pp. 12-15
Author(s):  
Alexander Meisel
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Treatment Strategies ◽  
Castration Resistant Prostate Cancer ◽  
Continuous Therapy ◽  
Castration Resistant ◽  
Literature Overview ◽  
Metastatic Prostate Carcinoma ◽  
Insight Into ◽  
Systemic Therapies

ABSTRACT In general, advanced prostate cancer is initially treated with androgen deprivation therapy (ADT). Despite high response rates to this treatment, the response is not durable and most of the patients eventually develop metastatic castration-resistant prostate cancer (mCRPC). The treatment strategies for mCRPC usually include a combination of different approaches, such as hormone therapy, chemotherapy, or radiation. Here, we discuss the case of a 78-year old patient with advanced prostate cancer who developed mCRPC after 4 years of continuous therapy with ADT. The patient was subsequently treated with analgesic radiotherapy, followed by chemotherapy, including docetaxel and cabazitaxel. The patient responded well to the treatment, with acceptable treatment-related toxicity. Three years later, however, the disease progressed, and the patient received anti-hormonal therapy with enzalutamide. In conclusion, this case report discusses the different therapy selections and outcomes. Finally, a literature overview offers a comprehensive insight into the current systemic therapies for mCRPC.

scholarly journals New Frontiers in Prostate Cancer Treatment: Are We Ready for Drug Combinations with Novel Agents?

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1522
Author(s):  
Gaetano Aurilio ◽  
Alessia Cimadamore ◽  
Matteo Santoni ◽  
Franco Nolè ◽  
Marina Scarpelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Care ◽  
Combined Treatment ◽  
Single Agent ◽  
Treatment Strategies ◽  
Drug Combinations ◽  
Clinical Approach ◽  
Castration Resistant Prostate Cancer ◽  
Keywords Prostate Cancer ◽  
Castration Resistant

Medical treatment for metastatic castration-resistant prostate cancer (mCRPC) patients has progressively been evolving from a nonspecific clinical approach to genomics-oriented therapies. The scientific community is in fact increasingly focusing on developing DNA damage repair (DDR) defect-driven novel molecules, both as single-agent therapy and in combined treatment strategies. Accordingly, research is under way into combined drug therapies targeting different pathways, e.g. androgen receptor signaling (ARS) and poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes, immune checkpoint (IC) and PARP, IC, and ARS, and prostate-specific membrane antigen (PSMA). In an attempt to formulate evolving treatment paradigms in mCRPC patients, here we selected clinical research into patients undergoing therapies with emerging molecules, with particular emphasis towards PARP-, IC-, and PSMA-inhibitors. In order to focus on those molecules and drug combinations most likely to be translated into routine clinical care in the near future, we selected only those clinical studies currently recruiting patients. A PubMed search focusing on the keywords “prostate cancer”, “metastatic castration-resistant prostate cancer”, “DDR pathways”, “ARS inhibitors”, “PARP inhibitors”, “IC inhibitors”, “PSMA-targeting agents”, and “drug combinations” was performed.

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.

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