scholarly journals The Quandary of DNA-Based Treatment Assessment in De Novo Metastatic Prostate Cancer in the Era of Precision Oncology

2021 ◽  
Vol 11 (5) ◽  
pp. 330
Author(s):  
Sigve Nakken ◽  
Wolfgang Lilleby ◽  
Marta D. Switlyk ◽  
Karen E. Knudsen ◽  
Oscar Lilleby ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Treatment Options ◽  
Expression Patterns ◽  
Precision Oncology ◽  
Mri Findings ◽  
Multiple Tumor ◽  
Somatic Aberrations

Guidelines for genetic testing have been established for multiple tumor types, frequently indicating the most confident molecularly targeted treatment options. However, considering the often-complex presentation of individual cancer patients, in addition to the combinatorial complexity and inherent uncertainties of molecular findings, deriving optimal treatment strategies frequently becomes very challenging. Here, we report a comprehensive analysis of a 68-year-old male with metastatic prostate cancer, encompassing pathology and MRI findings, transcriptomic results, and key genomics findings from whole-exome sequencing, both somatic aberrations and germline variants. We identify multiple somatic aberrations that are known to be enriched in prostate cancer, including a deletion of PTEN and a fusion transcript involving BRCA2. The gene expression patterns in the tumor biopsy were also strikingly similar to prostate tumor samples from TCGA. Furthermore, we detected multiple lines of evidence for homologous recombination repair deficiency (HRD), including a dominant contribution by mutational signature SBS3, which is specifically attributed to HRD. On the basis of the genomic and transcriptomic findings, and in light of the clinical case presentation, we discussed the personalized treatment options that exist for this patient and the various challenges that one faces in the process of translating high-throughput sequencing data towards treatment regimens.

scholarly journals PD34-12 MRI FINDINGS IN DE NOVO SYNCHRONOUS METASTATIC PROSTATE CANCER AND IMPLICATIONS FOR CYTOREDUCTIVE SURGERY

2021 ◽  
Vol 206 (Supplement 3) ◽  
Author(s):  
Martin John Connor ◽  
Marie Edison ◽  
Edward J. Bass ◽  
David Eldred-Evans ◽  
Mariana Tanaka Bertoncelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cytoreductive Surgery ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Mri Findings

scholarly journals Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer

2021 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
Ding-Wei Ye ◽  
Bo Dai ◽  
Jun-Yu Zhang ◽  
Yun-Yi Kong ◽  
Qi-Feng Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Value ◽  
Metastatic Prostate Cancer ◽  
De Novo

scholarly journals Vulpinic Acid as a Natural Compound Inhibits the Proliferation of Metastatic Prostate Cancer Cell by Inducing Apoptosis

2021 ◽  
Author(s):  
Demet Cansaran Duman ◽  
Gamze Guney Eskiler ◽  
Betül Çolak ◽  
Elif Sozen Kucukkara
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Annexin V ◽  
Current Treatment ◽  
Pcr Analysis ◽  
G1 Arrest ◽  
Advanced Analysis ◽  
Induced Apoptosis

Abstract Lichen secondary metabolites have drawn considerable attention in recent years due to limitations of current treatment options. Vulpinic acid (VA) obtained from Letharia vulpina lichen species exerts a remarkable cytotoxic effect on different cancer types. However, the therapeutic efficacy of VA in metastatic prostate cancer (mPC) cells has not been investigated. In the present study, we aimed to identify VA-mediated cytotoxicity in PC-3 mPC cells compared with control cells. After identification of the cytotoxic concentrations of VA, VA induced apoptosis was analyzed by Annexin V, cell cycle, acridine orange and propidium iodide staining and RT-PCR analysis. Our findings showed that VA significantly decreased the viability of PC-3 cells (p < 0.01) and caused a considerable early apoptotic effect through G0/G1 arrest, nuclear bleebing and the activation of particularly initiator caspases. Therefore, VA may be a potential treatment option for mPC patients. However, the underlying molecular mechanisms of VA-induced apoptosis with advanced analysis should be further performed.

Cytoreductive treatment strategies for de novo metastatic prostate cancer

2019 ◽  
Vol 17 (3) ◽  
pp. 168-182 ◽  
Author(s):  
Martin J. Connor ◽  
Taimur T. Shah ◽  
Gail Horan ◽  
Charlotte L. Bevan ◽  
Mathias Winkler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Treatment Strategies ◽  
Cytoreductive Treatment

Abstract LB-236: Genomic characterization of circulating tumor cells in de novo metastatic prostate cancer

2019 ◽  
Author(s):  
Shoujie Chai ◽  
Paymaneh D. Malihi ◽  
Ana M. Apariciop ◽  
Brian F. Chapin ◽  
Matthew Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Genomic Characterization

scholarly journals Local and systemic morbidities of de novo metastatic prostate cancer in Singapore: insight from 685 consecutive patients from a large prospective Uro-oncology registry

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e034331 ◽  
Author(s):  
Yu Guang Tan ◽  
Leonard Pang ◽  
Farhan Khalid ◽  
Randy Poon ◽  
Hong Hong Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Metastatic Prostate Cancer ◽  
Group Performance ◽  
De Novo ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
High Volume ◽  
Secondary Outcome ◽  
Systemic Complications

ObjectiveTo evaluate the incidence and management of local and systemic complications afflicting patients with de novo metastatic prostate cancer (mPCa) in Singapore.DesignRetrospective analysis of a large prospective Uro-oncology registry of mPCa.SettingThis study is carried out in a tertiary hospital in Singapore.ParticipantsWe reviewed our institution’s prospectively maintained database of 685 patients with mPCa over a 20-year period (1995–2014). Patients with non-mPCa or those progressed to metastatic disease after previous curative local treatments were excluded.Primary and secondary outcome measuresThe primary outcome was to evaluate the systemic and local morbidity rates associated with mPCa. Local complication was defined as the need for palliative procedures to relieve urinary obstruction, worsening renal function or refractory haematuria, while systemic complication was related to radiographic evidence of skeletal-related pathological fractures. Secondary outcomes analysed were the management and overall survival patterns over 20 years.Results237 (34.6%) patients required local palliative treatments. 88 (12.8%) patients presented with acute urinary retention, 23 patients (9.7%) required repetitive local palliative treatments. On multivariate analyses, prostate-specific antigen >100 (p=0.02) and prostate volume >50 g (p=0.03) were independent prognostic factors for significant obstruction requiring palliative procedures. 118 (17.2%) patients developed skeletal fractures, with poor Eastern Cooperative Oncology Group Performance (ECOG) status (p=0.01) and high volume bone metastasis (p<0.01) independently predictive of skeletal fractures. Altogether, 653 (95.3%) patients received androgen deprivation therapy (ADT), with the median time to castrate resistance of 21.4 months (IQR 7–27). The median overall survival was 45 months (IQR 20–63), with prostate cancer mortality of 81.4%. Improved overall survival was observed from 41.6 months (1995–1999) to 47.8 months (2010–2014) (p<0.01).ConclusionMorbidities and complications arising from mPCa are more common and debilitating than we thought, often requiring immediate palliative treatments, while many necessitate repeated interventions with progression.

scholarly journals Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

2020 ◽  
pp. 882-897 ◽  
Author(s):  
Clare Gilson ◽  
Fiona Ingleby ◽  
Duncan C. Gilbert ◽  
Marina A. Parry ◽  
Nafisah B. Atako ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromatin Remodeling ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
High Volume ◽  
Pi3k Pathway ◽  
Mismatch Repair Gene ◽  
Copy Number Loss ◽  
Hormone Sensitive ◽  
Low Volume

PURPOSE The STAMPEDE trial recruits men with newly diagnosed, high-risk, hormone-sensitive prostate cancer. To ascertain the feasibility of targeted next-generation sequencing (tNGS) and the prevalence of baseline genomic aberrations, we sequenced tumor and germline DNA from patients with metastatic prostate cancer (mPCa) starting long-term androgen-deprivation therapy (ADT). METHODS In a 2-stage approach, archival, formalin-fixed, paraffin-embedded (FFPE) prostate tumor core biopsy samples were retrospectively subjected to 2 tNGS assays. Prospective enrollment enabled validation using tNGS in tumor and germline DNA. RESULTS In stage 1, tNGS data were obtained from 185 tumors from 287 patients (65%); 98% had de novo mPCa. We observed PI3K pathway aberrations in 43%, due to PTEN copy-number loss (34%) and/or activating mutations in PIK3 genes or AKT (18%) and TP53 mutation or loss in 33%. No androgen receptor ( AR) aberrations were detected; RB1 loss was observed in < 1%. In stage 2, 93 (92%) of 101 FFPE tumors (biopsy obtained within 8 months) were successfully sequenced prospectively. The prevalence of DNA damage repair (DDR) deficiency was 14% (somatic) and 5% (germline). BRCA2 mutations and mismatch repair gene mutations were exclusive to high-volume disease. Aberrant DDR (22% v 15%), Wnt pathway (16% v 4%), and chromatin remodeling (16% v 8%) were all more common in high-volume compared with low-volume disease, but the small numbers limited statistical comparisons. CONCLUSION Prospective genomic characterization is feasible using residual diagnostic tumor samples and reveals that the genomic landscapes of de novo high-volume mPCa and advanced metastatic prostate cancer have notable similarities (PI3K pathway, DDR, Wnt, chromatin remodeling) and differences ( AR, RB1). These results will inform the design and conduct of biomarker-directed trials in men with metastatic hormone-sensitive prostate cancer.

Patterns of second-line chemotherapy for metastatic prostate cancer in the United States.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 169-169
Author(s):  
Hongwei Wang ◽  
Laura Liao ◽  
Eliot Obi-Tabot ◽  
Robert Sands ◽  
Mathieu Rose ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Healthcare Costs ◽  
Metastatic Prostate Cancer ◽  
Hospital Admissions ◽  
Treatment Options ◽  
Patient Characteristics ◽  
The United States ◽  
Geographic Region ◽  
Treatment Groups ◽  
Comorbidity Burden

169 Background: Patients with prostate cancer progressing from 1st line (1L) docetaxel had limited treatment options available. This study is to evaluate patterns of 2nd line (2L) chemotherapy in US managed care between 2004 and 2010. Methods: Patients with metastatic prostate cancer (mPC) and treated with docetaxel as 1L chemotherapy after July 1, 2004 were ascertained from the OptumInsight database. We evaluated type and timing of chemotherapy and relationships between patient characteristics, physician specialty, healthcare costs and geographic region 6 months prior to 1L docetaxel and choice of 2L chemotherapy. Results: Patients (n=1,173) were on average 71 years old at the onset of 1L docetaxel. During a mean follow-up period of 18 months, 38% patients received 2L treatment. Out of the patients received 2L therapy, 32% received mitoxantrone (MITO), 24% with docetaxel rechallenge (RECH), 14% carboplatin (CARB), and 12% paclitaxel (PAC), plus 11% on combo therapy. An examination of the 2L treatment groups showed that during the 6 months prior to 1L docetaxel, the RECH group (n=101) was older (73yrs), had fewer hospital admissions (12%), lower comorbidity burden (Charlson Comorbidity Index (CCI)=7.4), lower total healthcare costs ($10,083), and 78% patients seeing an oncologist; relative to MITO group (n=143) with 70 years of age, 16% hospital admissions, CCI of 7.5, total healthcare costs of $12,074, and 80% seeing an oncologist. The combo group (n=52) was 66 years old, with 19% hospital admissions, CCI of 8, total healthcare costs of $20, 505, and 92% seeing an oncologist. Median time to MITO from the start of 1L docetaxel was 184 days, 309 days to RECH and 223 days to combo therapy. Midwest (36%) and West (37%) were more frequently using MITO than Northeast (26%) and South (31%), while RECH was more frequently used in Northeast. Conclusions: Patients with mPC in US were most frequently treated with MITO or RECH as 2L chemotherapy after 1L docetaxel. MITO was also given sooner than RECH, hence a valid comparator for comparative effectiveness evaluation on new 2L therapy. Rechallenge with docetaxel increased with time and was given to patients with lower disease burden and healthcare costs than the MITO or Combo group.

Age, race, and survival of men with de novo distant metastatic prostate cancer (M1PC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5031-5031 ◽  
Author(s):  
Brandon David Bernard ◽  
Jennifer R. Rider ◽  
Christopher Sweeney ◽  
Srikala S. Sridhar
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
De Novo
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