Brachytherapy Alone May Be Sufficient For Most Early Prostate Cancer Patients

13 Background: Whole genome and matching normal tissue analyses in prostate cancer patients have shown that widespread genomic changes occur in multiple distant regions of the genome simultaneously (Baca et al., Cell. 2013). The inherent genomic instability in prostate cancers causes activation of pathways involved in DNA damage, which could be a prognostic and potentially predictive marker for treatment with agents impacting DNA repair (e.g. PARP inhibitors). Using a published dataset, a “DNA damage signature” was generated to test its role as a potential prognostic marker. Methods: A 10-gene signature was generated, using the top 9 genes (MXD3, ZMYND19, BANF1, TOMM40, UBE2S, SNRPF, RPP21, CDK2AP2 and H2AFX) correlated with H2AFX expression, which is known to be unregulated upon DNA damage. TP53 was added due to its significant role in this pathway. This signature was then assessed in The Cancer Genome Atlas dataset (TCGA, unpublished data at NCI) as a discovery set and then validated in the MSK dataset (Taylor et al., 2010) using mutation, copy number, mRNA and proteomic data. Results: Genes in the signature were altered in 31% (77/246) of patients, by amplification and over expression compared to normal. The most frequent alterations were found in TP53 (15%), MXD3 (7%), BANF1 (7%), UBE28 (7%) and CDK2AF2 (7%). Analysis of protein changes associated with alteration in genomic signature showed upregulation of FOXO3, BCL2L1, BAK1 and PCNA (P<0.05). There were significant correlations between the signature and Gleason score (p=0.0015), PTEN (p=0.003) & RAD51 gene expression (p<0.001), but not with ERG,PSA, PIK3CA or BRCA2. Patients with alterations were associated with poor disease free survival (DFS) (p=0.002). When expression was assessed in the validation set, 73%(62/85) samples showed altered gene signatures and those with alterations also had poor DFS (p=0.003). Conclusions: The DNA damage signature can be used to define a group of patients with poor outcome and has the potential to be used as prognostic marker in treatment decisions in early prostate cancer patients.

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The psychological impact of early prostate cancer: A prospective evaluation.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.210 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 210-210

Author(s):

Hadas Dresler ◽

Daniel Keizman ◽

David Sarid ◽

Debi Oren

Keyword(s):

Quality Of Life ◽

Prostate Cancer ◽

Psychological Distress ◽

Cancer Patients ◽

Illness Perception ◽

Psychological Impact ◽

Good Prognosis ◽

Healthy Controls ◽

Early Prostate Cancer

210 Background: Early prostate cancer is often considered as being associated with a good prognosis and quality of life. However, early prostate cancer research mainly focus on its medical aspects, rarely considering its psychological impact. We aimed to prospectively analyze the correlation between illness perception, quality of life (QOL) and psychological distress among prostate cancer patients, in comparison to healthy controls. Methods: Early prostate cancer patients and healthy controls were prospectively recruited through convenience sampling. Participants filled questionnaires of demographic, illness perception (IPQ-R), QOL (MOS SF-36) and anxiety and depression (HADS). We compared the illness perception, QOL and psychological distress between patients and healthy controls. Results: 51 early prostate cancer patients and 65 healthy men controls were included. Median age was 69. Patients and healthy participants differed in illness perception ['consequences' (p<.001), 'emotional representations' (p<.001)] and psychological distress (p<.01). There was a correlation between the patient illness perception and QOL (p<.05) and psychological distress (p<.05). Among patients, the correlation between psychological distress and QOL was mediated by illness perception (p<.05), while it was not among controls. Conclusions: Diagnosis of early prostate cancer may have a psychological impact. Among early prostate cancer patients, a correlation may exist between illness perception, and quality of life (QOL) and psychological distress. Our results emphasize the need to identify patient distress and to implement therapeutic interventions also in a disease which usually is associated with a good prognosis.

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