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 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.

Comprehensive analysis of serum chromogranin A and neuron‐specific enolase levels in localized and castration‐resistant prostate cancer

2020 ◽  
Vol 127 (1) ◽  
pp. 44-55 ◽  
Author(s):  
Tibor Szarvas ◽  
Anita Csizmarik ◽  
Tamás Fazekas ◽  
András Hüttl ◽  
Péter Nyirády ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Neuron Specific Enolase ◽  
Comprehensive Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

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 Identification of Novel Diagnosis Biomarkers for Therapy-Related Neuroendocrine Prostate Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Cuijian Zhang ◽  
Jinqin Qian ◽  
Yucai Wu ◽  
Zhenpeng Zhu ◽  
Wei Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Characteristics ◽  
Expression Profiles ◽  
Prostate Adenocarcinoma ◽  
Diagnostic Tools ◽  
Receptor Interaction ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Platinum Based Chemotherapy

Background: Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks well-characterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing anti-androgen receptor therapy or switching to platinum-based chemotherapy.Methods: Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset.Results: A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively.Conclusion: The present study identified four specific novel biomarkers for therapy-related NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.

Evaluation of oral cyclophosphamide activity by CTC enumeration in patients with docetaxel-refractory castration-resistant metastatic prostate cancer: Potential utility in primary refractory disease.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 166-166
Author(s):  
O. B. Goodman ◽  
J. T. Symanowski ◽  
L. M. Fink ◽  
N. J. Vogelzang
Keyword(s):  
Prostate Cancer ◽  
Circulating Tumor Cell ◽  
Fisher Exact Test ◽  
Complete Disappearance ◽  
Oral Cyclophosphamide ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Exact Test ◽  
Castration Resistant ◽  
Limited Experience

166 Background: Recent data suggest that circulating tumor cell (CTC) enumeration is a surrogate predictive endpoint for survival in metastatic castration-resistant prostate cancer (mCRPC). Data supporting the notion of changing therapy from docetaxel based on CTC numbers is limited in PC, due to a limited experience with second-line systemic therapies following docetaxel failure. Methods: Peripheral blood from patients receiving cyclophosphamide following progression on docetaxel was analyzed by CellSearch Methodology (Veridex, LLC; Warren NJ) enumerate CTC. Circulating tumor cells were enumerated prior to and at least three weeks following the initiation of cyclophosphamide. Patients were categorized as responsive, defined as a follow up CTC of <5 cells or a greater than a 90% decline in counts between CTC determinations, or refractory (all others). Cyclophosphamide responsiveness was then correlated with docetaxel responsiveness using a Fisher-exact test. Results: Twenty two patients received oral cyclophosphamide therapy (50-150 mg/day). Of these, twelve (55%) were clinically primary docetaxel refractory, assessed by either clinical or PSAWG2 criteria while on docetaxel, and ten (45%) were initially responsive but subsequently progressed on docetaxel. Of the twelve patients who were primarily refractory to docetaxel, seven (58%) exhibited a cyclophosphamide response. In the majority of these cases, this response was durable with a complete disappearance of CTC. Conversely, only one patient (10%) who initially responded to docetaxel was sensitive to cyclophosphamide (P=0.031). Conclusions: Using a CTC endpoint cyclophosphamide appears to be active in patients initially refractory to docetaxel, but not those who initially responded. These data support the further evaluation of the potential for selective clinical utility of cyclophosphamide as second-line chemotherapy. [Table: see text]

scholarly journals Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological and Immunohistochemical Analysis of 94 Cases

2021 ◽  
Vol 10 ◽  
Author(s):  
Qingfu Zhang ◽  
Yunan Han ◽  
Yao Zhang ◽  
Dan Liu ◽  
Jian Ming ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Stage Iv ◽  
Immunohistochemical Analysis ◽  
Prostate Adenocarcinoma ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Neuroendocrine Prostate Cancer

PurposeThis study aimed to evaluate the pathological characteristics, immunophenotype, and prognosis of treatment-emergent neuroendocrine prostate cancer (T-NEPC).Materials and MethodsWe collected 231 repeated biopsy specimens of castration-resistant prostate cancer (CRPC) cases between 2008 and 2019. We used histopathological and immunohistochemical evaluations of Synaptophysin (SYN), ChromograninA (CgA), CD56, androgen receptor (AR), and prostate-specific antigen (PSA) to screen out T-NEPC cases. Multivariate analyses were performed to identify factors in the prognosis of T-NEPC. Further, the results were verified in the Surveillance, Epidemiology, and End Results (SEER) program.ResultsAmong the 231 CRPC cases, 94 (40.7%) cases were T-NEPC. T-NEPC were more likely to present with negative immunohistochemistry for AR (30.9%) and PSA (47.9%) than that of CRPC (8.8% and 17.5%, respectively). Kaplan-Meier analysis revealed that patients with T-NEPC (median overall survival [OS]: 17.6 months, 95% CI: 15.3–19.9 months) had significantly worse survival compared with usual CRPC patients (median OS: 23.6 months, 95% CI: 21.3-25.9 months, log-rank P = 0.001), especially in metastasis cases (median OS: 15.7 months, 95% CI: 13.3-18.0 months) and patients with small cell carcinoma component (median OS: 9.7 months, 95% CI: 8.2–11.2 months). Prostate adenocarcinoma with diffuse NE differentiation (median OS: 18.8 months, 95% CI: 15.3–22.3 months) had poor outcome than those with usual CRPC (P = 0.027), while there was no significant change in the focal NE differentiation (median OS: 22.9 months, 95% CI: 18.1–27.7 months, P = 0.136). In the unadjusted model, an excess risk of overall death was observed in T-NEPC with PSA negative (HR = 2.86, 95% CI = 1.39–6.73). Among 476 NEPC cases in the SEER database from 2004 to 2017, we observed a higher hazard of overall death in patients aged 65 years and older (HR = 1.35, 95% CI = 1.08–1.69), patients with PSA ≤ 2.5 ng/ml (HR = 1.90, 95%CI = 1.44–2.52), patients with PSA 2.6–4.0 ng/ml (HR = 2.03, 95%CI = 1.38–2.99), stage IV tumor (HR = 2.13, 95%CI = 1.47–3.08) and other races (HR = 1.85, 95%CI = 1.17–2.94) in total NEPC, adjusting for confounders. Similar hazard ratios were observed in pure NEPC, while there was no significant results among prostate adenocarcinoma with NE differentiation tumors.ConclusionT-NEPC was associated with an unfavorable prognosis, negative immunohistochemistry for PSA in T-NEPC and serum PSA level ≤ 4 ng/ml had a worse prognosis. Urologists and pathologists should recognize the importance of the second biopsy in CRPC to avoid unnecessary diagnosis and treatment delays.

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]

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.

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