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

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.

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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

JCO Precision Oncology ◽

10.1200/po.19.00388 ◽

2020 ◽

pp. 882-897 ◽

Cited By ~ 2

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.

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MP87-19 MULTIMODAL SYSTEMIC THERAPY WITH DEFINITIVE PROSTATECTOMY IN DE NOVO METASTATIC PROSTATE CANCER

The Journal of Urology ◽

10.1016/j.juro.2018.02.2919 ◽

2018 ◽

Vol 199 (4S) ◽

Author(s):

Ramkishen Narayanan ◽

Jennifer Linehan ◽

Nicholas Vogelzang ◽

Chikako Matsuba ◽

Przemyslaw Twardowski ◽

...

Keyword(s):

Prostate Cancer ◽

Systemic Therapy ◽

Metastatic Prostate Cancer ◽

De Novo

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Survival outcomes for de novo versus primary progressive metastatic prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.258 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 258-258

Author(s):

Kanika Gupta ◽

Antoine Nafez Finianos ◽

Brandon Clark ◽

Samuel J. Simmens ◽

Jeanny B. Aragon-Ching

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Metastatic Prostate Cancer ◽

De Novo ◽

Retrospective Chart Review ◽

Receptor Expression ◽

Age At Diagnosis ◽

Castration Resistance ◽

Phenotypic Characteristics ◽

Primary Progressive

258 Background: We reported initial findings on the phenotypic differences between de novo versus primary progressive metastatic prostate cancer (Finianos et al., ASCO GU; abstr 285). We sought to determine the differences in the phenotypic characteristics of these 2 cohorts of patients and update the data with overall survival and patterns of response to androgen deprivation therapy (ADT) in patients presenting with de novo versus primary progressive prostate cancer. Methods: A retrospective chart review in a single-institution center for a period of 2 years was undertaken. Phenotypic characteristics included age at diagnosis, race, overall survival, treatment patterns, and response to ADT. Analysis was by t-test, Mann-Whitney U test, and Fisher’s Exact test. Results: A total of 90 patients were included in this cohort with de novo, dn (n = 38) and primary progressive, pp (n = 52) patients. There were no significant differences between the 2 cohorts with regard to the median age at diagnosis (dn = 66, pp = 61, p = 0.11), alkaline phosphatase level (dn = 135.5, pp = 86, p = 0.27), BMI (dn = 28.47, pp = 27, p = 0.78), creatinine (dn = 1.02, pp = 0.99, p = 0.34), LDH (dn = 188, pp = 166, p = 0.34), and testosterone on metastasis (dn = 276, pp = 31, p = 0.16). However, de novo cancers were diagnosed with higher mean gleason scores (dn = 8.36, pp = 7.7, p = 0.004), had higher median PSA upon diagnosis (dn = 63.1, pp = 8.8, p < .0001) and higher PSA on metastasis (dn = 61.7, pp = 12.5, p = .0002), and had a statistically significant decreased duration of hormone sensitivity (dn = 642 days, pp = 1783 days, p = < .0001). Patients with d e novo cancers also had a shorter median survival than primary progressive cancers (dn = 2257 days, pp = 4217 days, p = 0.02). Conclusions: Patients who present with de novo metastatic prostate cancer appear to develop early castration resistance and have worse overall survival than those who present with primary progressive disease. We are exploring the molecular differences in terms of androgen receptor expression as a potential etiology for development of early castration resistance.

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