SPOP mutations in prostate cancer: Clinical and genomic features.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 151-151
Author(s):  
Mari Nakazawa ◽  
Mike Fang ◽  
Pedro Issacsson Velho ◽  
Emmanuel S. Antonarakis
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Metastatic Disease ◽  
Wnt Pathway ◽  
Zinc Finger Protein ◽  
De Novo ◽  
First Line ◽  
Primary Tumors ◽  
Pathway Activation ◽  
Prostate Cancers

151 Background: Point mutations in the gene encoding speckle-type pox virus and zinc finger protein (SPOP) are the most frequently identified mutations in prostate cancer, occurring at a frequency of 6-15% across localized and disseminated cancers. Recently, SPOP gene alterations have gained attention as they appear to define a novel subclass of prostate cancers. Previous studies show that patients with mutant SPOP (mtSPOP) had superior responses to androgen deprivation therapy (ADT) and exhibit more favorable responses to abiraterone compared to wild type SPOP (wtSPOP). Methods: We retrospectively identified 59 prostate cancer patients at a single institution (Johns Hopkins) with somatic SPOP mutations from genomic testing of primary tumors (n=45), metastatic lesions (n=12), or liquid biopsies (n=2). Patient records were reviewed to determine baseline characteristics, therapies received, and clinical outcomes. The primary outcomes included best PSA response and progression-free survival (PFS) on ADT in the hormone sensitive prostate cancer (HSPC) setting and on abiraterone and/or enzalutamide in the first-line castration resistant prostate cancer (CRPC) setting. PFS was defined as either PSA, radiographic, or clinical progression. Results: The median age at diagnosis was 64 years (range 46 to 85). 17/59 (28.8%) were Black. F133 was the most frequently mutated residue, occurring in 33 (55.9%) instances (Table). There were two patients who harbored two mutations in the SPOP gene. The most frequently co-occurring mutation was in APC (15/59 [25.4%] patients), resulting in Wnt pathway activation. Concurrent ERG fusions were not observed with this cohort (0/59 [0%] patients). 41/59 (69.4%) were diagnosed with Gleason 8-10 disease. 21/59 (35.5%) were diagnosed with de novo metastatic disease. 50/59 (84.7%) patients received ADT for recurrent or metastatic disease. Median PFS on ADT was 40.7 (95% CI 23.4-71.9) months. Of the 27/59 (45.8%) patients who progressed to CRPC, 20/59 (33.9%) patients received abiraterone and 13/59 (22.0%) received enzalutamide; 9/59 (15.3%) patients received both agents. Median PFS was 7.8 (95% CI 6.7-NR) months on abiraterone and 7.3 (95% CI 3.2-NR) months on enzalutamide. Other notable therapies received in the CRPC setting include docetaxel (5/59 [8.5%] patients), cabazitaxel (5/59 [8.5%] patients), and PARP inhibitor olaparib or rucaparib (4/59 [6.8%] patients). Conclusions: SPOP mutations define a unique subset of prostate cancers enriched for black patients, high Gleason scores, absence of ERG fusions, and Wnt pathway activation. Clinical outcomes to first-line ADT appear longer than expected for genomically-unselected patients. [Table: see text]

scholarly journals Optimal Treatment for Patients with Oligometastatic Prostate Cancer

2021 ◽  
pp. 1-10
Author(s):  
Bulent Cetin ◽  
Chiara A. Wabl ◽  
Ozge Gumusay
Keyword(s):  
Prostate Cancer ◽  
Metastatic Disease ◽  
De Novo ◽  
Optimal Treatment ◽  
Survival Outcomes ◽  
Appendicular Skeleton ◽  
Oncological Outcomes ◽  
Oligometastatic Prostate Cancer

Oligometastatic prostate cancer (PCa) can be defined as cancer with a limited number of metastases, typically fewer than 5 lesions, and involves lesions contained within the axial versus the appendicular skeleton. Patients can present with de novo oligometastatic, oligorecurrent, or oligoprogressive PCa. Oligometastatic PCa patients demonstrate considerable improvements in survival outcomes, with a better prognosis than patients with extensive metastatic disease. However, the management of patients that present with nonsymptomatic oligometastatic PCa remains difficult. In the oligometastatic setting, the benefit of local therapies such as prostatectomy and radiotherapy on survival outcomes is an intriguing topic; however, their impact on oncological outcomes is still unknown.

Multi-institutional evaluation of the clinical outcomes and genomic correlates of African Americans with metastatic castration-sensitive prostate cancer (mCSPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 17-17
Author(s):  
Meredith MI Freeman ◽  
Ellen Jaeger ◽  
Jason Zhu ◽  
Audrey Phone ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retrospective Analysis ◽  
Clinical Outcomes ◽  
De Novo ◽  
High Volume ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Treatment Intensification ◽  
Radium 223 ◽  
Incidence And Mortality

17 Background: Prostate cancer incidence and mortality is higher in African American (AA) as compared with non-AA men. The outcomes of mCSPC have significantly improved through treatment intensification yet, AA representation in those studies was suboptimal. We aimed to report the clinical, treatment outcomes and genomic data of AA men with mCSPC. Methods: Retrospective analysis of consecutive AA men with mCSPC at six Academic Institutions. The primary objective was to report the baseline characteristics and treatment patterns of mCSPC AA patients. The secondary objectives included the germline and somatic data and the clinical outcomes including PSA response, progression-free survival and subsequent treatments. Results: A total of 71 patients, median age 63 years (range, 41-84) with 58% Gleason 8-10, initial PSA of 69.8 ng/mL (0.02-7650), 59% with de-novo and 55% with high-volume (CHAARTED criteria; 20% visceral) disease, were included in this analysis. Twenty-two patients (31%) were treated with androgen deprivation therapy (ADT; 67% prior to year 2017), while 24%, 45% and 3% received docetaxel (median 6 cycles), abiraterone acetate and enzalutamide, respectively. Two patients received triplet therapy with ADT/docetaxel plus abiraterone or enzalutamide. Undetectable PSA was achieved in 35% after a median of 8.9 months (1.8-22.3). Among patients with mCSPC who received radiation therapy to prostate (n = 8), 89% had low volume disease. At time of cut off, thirty-two patients developed CRPC and the estimated median time to CRPC was 2.9 years (95% CI, 1.6-4.2). Subsequent therapies (n = 29) included abiraterone acetate (41%), enzalutamide (24%), bicalutamide (10%), radium-223 (7%), chemotherapy (7%), sipuleucel-T (3%) and others (7%). Five patients (8%) had pathogenic germline alterations (n = 2 BRCA1; n = 1 HOXB13, PALB2 and PMS2). Additionally, the most common somatic alterations among tested patients (n = 27) included CDK12, SPOP, TMPRSS2-ERG fusion, and TP53, all in 11% frequency. Of note, n = 2 BRCA1 and n = 1 high MSI/TMB. Conclusions: In one of the largest reported cohorts to our knowledge, mCSPC AA presented with a high number of de-novo and high-volume disease and might harbor a different germline and somatic genomic profile. The outcomes were comparable to contemporary phase III trials with treatment intensification, yet 31% were treated with ADT. Despite the known limitations associated with retrospective analysis, these data support prior observations where AA might have better initial PSA responses to ADT-based strategies compared with Caucasians, requiring further validation.

scholarly journals Neurotensin Receptor-1 Expression in Human Prostate Cancer: A Pilot Study on Primary Tumors and Lymph Node Metastases

2019 ◽  
Vol 20 (7) ◽  
pp. 1721 ◽  
Author(s):  
Clément Morgat ◽  
Adrien Chastel ◽  
Vincent Molinie ◽  
Romain Schollhammer ◽  
Gaétan Macgrogan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
Distant Metastases ◽  
Human Prostate ◽  
Normal Prostate ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph ◽  
Prostate Cancers

Neurotensin and its high-affinity receptor, NTR1, are involved in the growth of various tumors. Few data are available regarding NTR1 expression in normal and tumoral human prostate tissue samples. NTR1 expression was assessed using immunohistochemistry in 12 normal prostate tissues, 11 benign prostatic hyperplasia (BPH), 44 prostate cancers, and 15 related metastatic lymph nodes (one per patient, when available). NTR1-staining was negative in normal prostate and BPH samples. NTR1 was overexpressed in four out of 44 (9.1%) primary tumors. There was no clear association between NTR1 overexpression and age, PSA-values, Gleason score, pT-status, nodal-status, or margin. NTR1 was expressed at a high level of five out of 15 (33.3%) metastatic lymph nodes. NTR1 overexpression was thus more frequent in metastatic lymph nodes than in primary tumors (p = 0.038). In this limited series of samples, NTR1 overexpression was observed in few primary prostate cancers. Upregulation was more frequent in related lymph nodes. The presence of this target in metastatic lymph nodes may open new perspectives for imaging and radionuclide therapy of prostate cancer. Factors driving NTR1 expression in primary prostate cancer and in nodal and distant metastases still need to be characterized.

Patterns of metastatic disease progression after treatment with first-line enzalutamide or abiraterone in castration-resistant prostate cancer (CRPC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e16539-e16539 ◽  
Author(s):  
Elizabeth K Lee ◽  
Benjamin A. Teply ◽  
Benjamin Louis Maughan ◽  
Michael Anthony Carducci ◽  
Emmanuel S. Antonarakis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Metastatic Disease ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant

Readiness of health care systems to generate RWE: Frequency of radiographic imaging of metastatic disease during first-line systemic therapy.

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 268-268
Author(s):  
Brandon Chan ◽  
David Cameron ◽  
Aria Shokoohi ◽  
Dean Regier ◽  
Howard John Lim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Health Care ◽  
Clinical Practice ◽  
Metastatic Disease ◽  
Real World ◽  
Systemic Therapy ◽  
De Novo ◽  
Metastatic Breast ◽  
Ct Imaging ◽  
First Line

268 Background: Regulatory and Health Technology Assessment (HTA) agencies are increasingly using real world data (RWD) to support real world evidence (RWE), but the readiness of healthcare systems to reliably generate RWE is unknown. As a quality assurance measure we examined the preparedness of a single payer system to provide RWE by evaluating the frequency of CT imaging during standard first line metastatic systemic treatment of breast, colorectal (CRC) and lung cancer. Methods: A 1-year cohort of de novo metastatic breast, CRC, lung cancer patients treated with first line systemic therapy (excluding hormone therapy) referred to BC Cancer in 2016 was retrospectively reviewed. Duration of first line treatment was calculated from first to last dose of therapy. Baseline CT included imaging within 8 weeks prior to and 3 weeks after treatment initiation (first cycle). Last CT included imaging up to 8 weeks after the last dose of therapy. Results: A cohort of 675 patients was identified from the BC Cancer Registry. The distribution of de novo metastatic disease at diagnosis was lung (n = 379), CRC (n = 214) followed by breast cancer (n = 82). Conclusions: In our publicly funded health care system, baseline CT scans within 4 weeks prior to treatment ranged from 57-72%. The median CT imaging interval during first line metastatic treatment was ranged from 7.9-11.3 weeks. RWD from routine clinical practice differs significantly from clinical trials, the gold standard for regulatory and HTA assessments. Population-based data may contribute to RWE with caution due to limitations imposed by clinical practice. [Table: see text]

scholarly journals Prostate cancer presented with de novo brain metastases as initial manifestation: A case report with review of the literature

2021 ◽  
Vol 5 (1) ◽  
pp. 01-04
Author(s):  
Konstantinos Tsapakidis
Keyword(s):  
Prostate Cancer ◽  
Brain Metastases ◽  
De Novo ◽  
Clinical Symptoms ◽  
Neurological Symptoms ◽  
Review Of The Literature ◽  
Initial Manifestation ◽  
Common Cancer ◽  
Advanced Stages ◽  
Prostate Cancers

Prostate cancer is the most common cancer and among the leading causes of cancer death in men and its clinical symptoms vary a lot. The most common metastatic site is the bones, but rarely prostate cancer can metastasize to brain in very advanced stages of the disease. However, brain metastases giving neurological symptoms as first manifestation of prostate cancers have been reported. Research of international literature revealed only seventeen patients (including our own) that were diagnosed with prostate cancer presented with neurological symptoms.

scholarly journals Clinical Outcomes of Combined Prostate- and Metastasis-Directed Radiation Therapy for the Treatment of De Novo Oligometastatic Prostate Cancer

2020 ◽  
Vol 5 (6) ◽  
pp. 1213-1224
Author(s):  
Brandon S. Imber ◽  
Melissa Varghese ◽  
Debra A. Goldman ◽  
Zhigang Zhang ◽  
Richard Gewanter ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Clinical Outcomes ◽  
De Novo ◽  
Oligometastatic Prostate Cancer

scholarly journals HLA Class I Allele Expression and Clinical Outcome in De Novo Metastatic Prostate Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1623
Author(s):  
Savvas Stokidis ◽  
Sotirios P. Fortis ◽  
Paraskevi Kogionou ◽  
Theodoros Anagnostou ◽  
Sonia A. Perez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
De Novo ◽  
Hla Class I ◽  
Class I ◽  
Rapid Progression ◽  
Castration Resistance ◽  
Poor Overall Survival ◽  
Prognostic Relevance ◽  
Hla Class I Molecules

The prognostic value of human leukocyte antigen (HLA) class I molecules in prostate cancer (PCa) remains unclear. Herein, we investigated the prognostic relevance of the most frequently expressed HLA-A alleles in Greece (A*02:01 and HLA-A*24:02) in de novo metastatic hormone-sensitive PCa (mPCa), which is a rare and aggressive disease characterized by a rapid progression to castration-resistance (CR) and poor overall survival (OS), contributing to almost 50% of PCa-related deaths. We identified 56 patients who had either progressed to CR (these patients were retrospectively analyzed for the time to the progression of CR and prospectively for OS) or had at least three months’ follow-up postdiagnosis without CR progression and, thus, were prospectively analyzed for both CR and OS. Patients expressing HLA-A*02:01 showed poor clinical outcomes vs. HLA-A*02:01−negative patients. HLA-A*24:02−positive patients progressed slower to CR and had increased OS. Homozygous HLA-A*02:01 patients progressed severely to CR, with very short OS. Multivariate analyses ascribed to both HLA alleles significant prognostic values for the time to progression (TTP) to CR and OS. The presence of HLA-A*02:01 and HLA-A*24:02 alleles in de novo mPCa patients are significantly and independently associated with unfavorable or favorable clinical outcomes, respectively, suggesting their possible prognostic relevance for treatment decision-making in the context of precision medicine.

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