Clinical Outcomes of Combined Prostate-Directed and Metastasis-Directed Radiotherapy for Treatment of De Novo Oligometastatic Prostate Cancer

2019 ◽  
Vol 105 (1) ◽  
pp. S151-S152
Author(s):  
B.S. Imber ◽  
M. Varghese ◽  
R.M. Gewanter ◽  
B.R. Mychalczak ◽  
D. Gorovets ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
De Novo ◽  
Oligometastatic Prostate Cancer

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 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 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.

Stereotactic ablative radiation therapy for the treatment of oligometastatic prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5020-5020 ◽  
Author(s):  
Phuoc T. Tran ◽  
C. Leigh Moyer ◽  
Ryan Phillips ◽  
Noura Radwan ◽  
Ashley Ross ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Stereotactic Ablative Radiotherapy ◽  
High Dose ◽  
Free Survival ◽  
Local Progression ◽  
Oligometastatic Prostate Cancer

5020 Background: The importance of local treatment in oligometastatic prostate cancer (OPC) is unknown. Stereotactic ablative radiotherapy (SABR) is highly focused, high-dose radiation that is well suited for treatment of oligometastases. Here we report on the safety and preliminary clinical outcomes of SABR in a modern cohort of OPC men. Methods: Eighty four men who satisfied criteria of OPC diagnosed on imaging underwent consolidative SABR were then followed prospectively on our IRB approved registry by our GU multidisciplinary team. We collected demographic, clinical, toxicity and efficacy information. We examined the first 66 men in this preliminary report to allow for a minimum of 4.5 months follow-up. SABR was delivered in 1-5 fractions of 5-18 Gy. Kaplan-Meier method was used to assess local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir+2), distant progression free survival (DPFS), ADT-free survival (ADT-FS) and time-to-next intervention (TTNI). Results: Of the 66 OPC patients analyzed, 25 (38%) men presented as synchronous OPC and the remaining 41 had recurrent OPC. Median and mean follow-up was 61 and 66 weeks, respectively. Patient and disease factors as listed in the Table. Crude Grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no Grade > 2 toxicity. SABR was delivered to 134 metastases: 89 bone (66%), 40 nodal (30%) and 5 (4%) visceral metastases. Overall LPFS at 1-year was 92%. The bPFS and DPFS at 1-year were 69% and 69%, respectively. Median TTNI was not reached yet. Of the 18 men with hormone sensitive prostate cancer who had their ADT deferred, 11/18 (56%) remain free of disease following SABR (1-year ADT-FS was 78%) and in 17 castration resistant men, 11 had > 50% PSA declines with 1-year TTNI of 30% with a median of 45 weeks. Conclusions: Consolidative SABRfor OPCis feasible and well tolerated. The preliminary clinical outcomes in our series is limited by heterogeneity and size but our data suggests that this approach is worthy of further prospective study. [Table: see text]

Metastatic Castration-Sensitive Prostate Cancer: Optimizing Patient Selection and Treatment

2018 ◽  
pp. 363-371 ◽  
Author(s):  
Andrew W. Hahn ◽  
Celestia S. Higano ◽  
Mary-Ellen Taplin ◽  
Charles J. Ryan ◽  
Neeraj Agarwal
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Treatment Options ◽  
Standard Of Care ◽  
Abiraterone Acetate ◽  
Multiple Treatment ◽  
High Risk Prostate Cancer ◽  
Oligometastatic Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Treatment Plans

The treatment landscape for metastatic castration-sensitive prostate cancer (mCSPC) has rapidly evolved over the past 5 years. Although androgen-deprivation therapy (ADT) is still the backbone of treatment, the addition of docetaxel or abiraterone acetate has improved outcomes for patients with mCSPC and become standard of care. With multiple treatment options available for patients with mCSPC, treatment selection to optimize patient outcomes has become increasingly difficult. Here, we review the clinical trials involving ADT plus docetaxel or abiraterone and provide clinicians with guidelines for treatment. Although surgery and/or radiation are standard of care for localized, intermediate- and high-risk prostate cancer, these treatments are not routinely used as part of initial treatment plans for patients with de novo mCSPC. Recent clinical data are challenging that dogma, and we review the literature on the addition of surgery and radiation to systemic therapy for mCSPC. Finally, the standard of care for oligometastatic prostate cancer (a subset of mCSPC with limited metastases) has not been established compared with that for some other cancers. We discuss the recent studies on metastasis-directed therapy for treatment of oligometastatic prostate cancer.

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]

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