Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/mm2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P \u3c .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned

Psychodynamic Experience Enhances Recognition of Hidden Childhood Trauma

BACKGROUND: Experimental psychology has only recently provided supporting evidence for Freud's and Janet's description of unconscious phenomena. Here, we aimed to assess whether specific abilities, such as personal psychodynamic experience, enhance the ability to recognize unconscious phenomena in peers - in other words, to better detect implicit knowledge related to individual self-experience. METHODOLOGY AND PRINCIPAL FINDINGS: First, we collected 14 videos from seven healthy adults who had experienced a sibling's cancer during childhood and seven matched controls. Subjects and controls were asked to give a 5-minute spontaneous free-associating speech following specific instructions created in order to activate a buffer zone between fantasy and reality. Then, 18 raters (three psychoanalysts, six medical students, three oncologists, three cognitive behavioral therapists and three individuals with the same experience of trauma) were randomly shown the videos and asked to blindly classify them according to whether the speaker had a sibling with cancer using a Likert scale. Using a permutation test, we found a significant association between group and recognition score (ANOVA: p = .0006). Psychoanalysts were able to recognize, above chance levels, healthy adults who had experienced sibling cancer during childhood without explicit knowledge of this history (Power = 88%; p = .002). In contrast, medical students, oncologists, cognitive behavioral therapists and individuals who had the same history of a sibling's cancer were unable to do so. CONCLUSION: This experiment supports the view that implicit recognition of a subject's history depends on the rater's specific abilities. In the case of subjects who did have a sibling with cancer during childhood, psychoanalysts appear better able to recognize this particular history

Psychodynamic Experience Enhances Recognition of Hidden Childhood Trauma

BACKGROUND: Experimental psychology has only recently provided supporting evidence for Freud's and Janet's description of unconscious phenomena. Here, we aimed to assess whether specific abilities, such as personal psychodynamic experience, enhance the ability to recognize unconscious phenomena in peers - in other words, to better detect implicit knowledge related to individual self-experience. METHODOLOGY AND PRINCIPAL FINDINGS: First, we collected 14 videos from seven healthy adults who had experienced a sibling's cancer during childhood and seven matched controls. Subjects and controls were asked to give a 5-minute spontaneous free-associating speech following specific instructions created in order to activate a buffer zone between fantasy and reality. Then, 18 raters (three psychoanalysts, six medical students, three oncologists, three cognitive behavioral therapists and three individuals with the same experience of trauma) were randomly shown the videos and asked to blindly classify them according to whether the speaker had a sibling with cancer using a Likert scale. Using a permutation test, we found a significant association between group and recognition score (ANOVA: p = .0006). Psychoanalysts were able to recognize, above chance levels, healthy adults who had experienced sibling cancer during childhood without explicit knowledge of this history (Power = 88%; p = .002). In contrast, medical students, oncologists, cognitive behavioral therapists and individuals who had the same history of a sibling's cancer were unable to do so. CONCLUSION: This experiment supports the view that implicit recognition of a subject's history depends on the rater's specific abilities. In the case of subjects who did have a sibling with cancer during childhood, psychoanalysts appear better able to recognize this particular history

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Genomic predictors for treatment of late stage prostate cancer

In spite of the development of new treatments for late stage prostate cancer, significant challenges persist to match individuals with effective targeted therapies. Genomic classification using high-throughput sequencing technologies has the potential to achieve this goal and make precision medicine a reality in the management of men with castrate-resistant prostate cancer. This chapter reviews some of the most recent studies that have resulted in significant progress in determining the landscape of somatic genomic alterations in this cohort and, more importantly, have provided clinically actionable information that could guide treatment decisions. This chapter reviews the current understanding of common alterations such as alterations of the androgen receptor and PTEN pathway, as well as ETS gene fusions and the growing importance of PARP inhibition. It also reviews recent studies that characterize the evolution to neuroendocrine tumors, which is becoming an increasingly important clinical problem. Finally, this chapter reviews recent innovative studies that characterize the compelling evolutionary history of lethal prostate cancer evidenced by polyclonal seeding and interclonal cooperation between metastasis and the importance of tumor clone dynamics measured serially in response to treatment. The genomic landscape of late stage prostate cancer is becoming better defined, and the prospect for assigning clinically actionable data to inform rationale treatment for individuals with this disease is becoming a reality

Brief assessment of priority symptoms in hormone refractory prostate cancer: The FACT Advanced Prostate Symptom Index (FAPSI)

Abstract Background The objective of this study was to construct and validate a brief, clinically-relevant symptom index for advanced prostate cancer. Methods Questions were extracted from a commonly-used multi-dimensional cancer quality of life instrument with prostate-specific items, the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Surveys of disease-related symptoms were presented to an international sample of 44 expert physicians. Each expert narrowed the list to no more than five of the most important symptoms or concerns to monitor when assessing the value of treatment for advanced prostate cancer. Symptoms/concerns endorsed at a frequency greater than chance probability (17%) were retained for the symptom index and called the FACT Advanced Prostate Symptom Index-8 (FAPSI-8): pain (three items), fatigue, weight loss, urinary difficulties (two items), and concern about the condition becoming worse. The FAPSI-8 was validated using data from a clinical trial of 288 men being treated for hormone refractory prostate cancer. Results The FAPSI-8 showed good internal consistency (r = 0.67–0.80); association with existing FACT scales (e.g., FACT-P, Physical Well-being, Functional Well-being; r = 0.44–0.85, p Conclusions This project produced a reliable and valid list of the eight most important clinician-rated targets of drug therapy for advanced prostate cancer. These questions perform comparably to the longer derivative questionnaire. Examination of patient agreement with this priority list and the extent to which changes in these 8 targets are related to meaningful clinical benefit to the patient are important next steps for future research.</p