A Systematic Review of the Association between Psychological Resilience and Improved Psychosocial Outcomes in Prostate Cancer Patients. Could Resilience Training Have a Potential Role?

PURPOSE: A high incidence of psychosocial problems in prostate cancer patients has been reported including anxiety, depression and distress. These can add to the patients' disease burden and have been associated with unfavorable cancer treatment outcomes. Interventions designed to address them have found limited success, but psychological resilience (PR) training has never been formally tested. The measurement of PR in prostate cancer patients has been described and has been associated with more favorable psychosocial outcomes in these patients but it has never been systematically reviewed. The aim of this study was to conduct the first systematic review of those studies that have measured it using standardized scales and to determine the potential for resilience training to help overcome the significant psychosocial problems faced by prostate cancer patients. MATERIALS AND METHODS: We searched the literature to identify articles that measured PR among prostate cancer patients. RESULTS: Of 384 articles identified by the search criteria, there were 19 studies suitable for inclusion regarding 5,417 patients. The most commonly-used scale was the original Connor-Davidson Resilience Scale, or an abbreviated version of it. Possible scores range from 0 to 100, mean scores from these studies ranged from 72.9 to 87.1 (standard deviations varied between 13.2 and 16.3). PR was consistently associated with improved psychological outcomes including depression, anxiety and distress, although these were measured with a wide variety of methods making it difficult to quantify the effects. There was also evidence of PR mediating the physical effects of prostate cancer and treatment including urinary symptoms, fatigue and insomnia. CONCLUSIONS: As resilience training has been successful in other cancer settings, it seems likely that it could improve the significant adverse psychosocial outcomes that have been reported in prostate cancer patients and trials designed to objectively test it should be encouraged.

Prostate Cancer Survivorship Essentials for men with prostate cancer on androgen deprivation therapy: protocol for a randomised controlled trial of a tele-based nurse-led survivorship care intervention (PCEssentials Hormone Therapy Study).

INTRODUCTION: Androgen deprivation therapy (ADT) is commonly used to treat men with locally advanced or metastatic prostate cancer. Men receiving ADT experience numerous side effects and frequently report unmet supportive care needs. An essential part of quality cancer care is survivorship care. To date, an optimal effective approach to survivorship care for men with prostate cancer on ADT has not been described. This protocol describes a randomised trial of tele-based nurse-led survivorship that addresses this knowledge gap: (1) determine the effectiveness of a nurse-led survivorship care intervention (PCEssentials), relative to usual care, for improving health-related quality of life (HR-QoL) in men with prostate cancer undergoing ADT and (2) evaluate PCEssentials implementation strategies and outcomes, including cost-effectiveness, compared with usual care. METHODS AND ANALYSIS: This is an effectiveness-implementation hybrid (type 1) trial with participants randomised to one of two arms: (1) minimally enhanced usual care and (2) nurse-led prostate cancer survivorship essentials (PCEssentials) delivered over four tele-based sessions, with a booster session 5 months after session 1. Eligible participants are Australian men with prostate cancer commencing ADT and expected to be on ADT for a minimum of 12 months. Participants are followed up at 3, 6 and 12 months postrecruitment. Primary outcomes are HR-QoL and self-efficacy. Secondary outcomes are psychological distress, insomnia, fatigue and physical activity. A concurrent process evaluation with participants and study stakeholders will be undertaken to determine effectiveness of delivery of PCEssentials. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Metro South Health HREC (HREC/2021/QMS/79429). All participants are required to provide written informed consent. Outcomes of this trial will be published in peer-reviewed journals. The findings will be presented at conferences and meetings, local hospital departments, participating organisations/clinical services, and university seminars, and communicated at community and consumer-led forums. TRIAL REGISTRATION NUMBER: ACTRN12622000025730.

Network connectivity between psychological resilience and depression in prostate cancer patients.

OBJECTIVES: Prostate cancer (PCa) patients often experience depression. One possible buffer against stress-related depression is psychological resilience (PR), which has been described as heterogeneous in structure, like major depressive disorder (MDD). Although both of these constructs are central to understanding and assisting distressed PCa patients, no data have been reported on how they connect via network arrays at a component and symptom level. Such information has the potential to inform clinical practice with depressed PCa patients. METHODS: Using a cross-sectional design, 555 PCa patients completed the Patient Health Questionnaire-9 (PHQ-9) and the Connor-Davison Resilience Scale (CDRISC). Data were analysed via network analysis. RESULTS: Network analysis indicated that various CDRISC factors interacted with different PHQ-9 symptoms. For example, trust in one's instincts, tolerance of negative affect, and strengthening effects of stress (CDRISC) was associated with concentration problems and suicidal ideation (PHQ-9); positive acceptance of change, and secure relationships (CDRISC) was linked to low self-worth, anhedonia, fatigue/lethargy, motor problems, depressed mood, and concentration and appetite problems (PHQ-9). Similarly heterogeneous associations were found between individual CDRISC items and PHQ-9 symptoms. Network analytic figures depict both these sets of associations. CONCLUSIONS: As well as confirming the heterogeneous nature of PR and MDD in PCa patients, these findings argue for the further development of 'individualised' medicine approaches when working with PCa patients and their experiences of depression.

Patterns of practice regarding use of radiation therapy following radical prostatectomy: A survey of Radiation Oncologists and Urologists in Australia and New Zealand.

INTRODUCTION: This study aimed to investigate the patterns of practices of radiation oncologists (ROs) and urologists in Australia and New Zealand with respect to the utilisation of post-prostatectomy radiation therapy (RT) and help guide the development of an update to the existing Faculty of Radiation Oncology Genito-Urinary Group post-prostatectomy guidelines. METHODS: ROs and urologists with subspecialty practice in prostate cancer from Australia and New Zealand were invited to participate in an online survey comprised of clinical scenarios regarding post-prostatectomy RT. RESULTS: Sixty-five ROs and 28 urologists responded to the survey. In the setting of low-risk biochemical relapse, the threshold for initiating RT was lower for ROs than urologists. ROs were more likely than urologists to recommend adjuvant RT for node-positive disease. When salvage RT was advised for a pT3N0R1 recurrence, there was no consensus amongst ROs on whether to add either ADT or nodal treatment over prostate bed RT alone. For a solitary PSMA-avid pelvic lymph node recurrence, whole pelvis RT with androgen deprivation therapy was the preferred treatment option (72% ROs, 43% urologists). Most ROs (92%) recommended conventionally fractionated RT to 66-70 Gy, with a boost to any PSMA PET avid recurrent disease. CONCLUSION: This survey highlights the marked discordance in practice for the management of prostate cancer relapse post-prostatectomy. This is seen not only between specialties but also within the radiation oncology community. This emphasises the need for an updated evidence-based guideline to be produced.

Network analysis of depression in prostate cancer patients: Implications for assessment and treatment.

OBJECTIVES: Many prostate cancer patients also suffer from depression, which can decrease their life satisfaction and also impede recovery from their cancer. This study described the network structure of depressive symptomatology in prostate cancer patients, with a view to providing suggestions for clinical interventions for depressed patients. METHODS: Using a cross-sectional design, 555 prostate cancer patients completed the Patient Health Questionnaire-9 (PHQ-9). RESULTS: Network analysis and multidimensional scaling indicated that anhedonia was the most central symptom for these men, and that several sets of depression symptoms were closely associated with each other. These included anhedonia-depressed mood; sleeping problems-fatigue/lethargy; and suicidal ideation-low self-worth-depressed mood. Other depression symptoms such as appetite problems, concentration problems, and motor problems, were less well-related with the remainder of the network. Patients receiving treatment for reocurring prostate cancer (PCa) had significantly higher PHQ9 scores than patients undergoing their initial treatment, but no major differences in their network structures. Implications for clinical practice were derived from the relationships between individual depression symptoms and the overall depression network by examining node predictability. CONCLUSIONS: The use of total depression scores on an inventory does not reflect the underlying network structure of depression in PCa patients. Identification and treatment of the central symptom of anhedonia in PCa patients suggests the need to adopt specific therapies that are focussed upon this symptom.

Drivers of Radioresistance in Prostate Cancer.

Prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide. Radiotherapy remains one of the first-line treatments in localised disease and may be used as monotherapy or in combination with other treatments such as androgen deprivation therapy or radical prostatectomy. Despite advancements in delivery methods and techniques, radiotherapy has been unable to totally overcome radioresistance resulting in treatment failure or recurrence of previously treated PCa. Various factors have been linked to the development of tumour radioresistance including abnormal tumour vasculature, oxygen depletion, glucose and energy deprivation, changes in gene expression and proteome alterations. Understanding the biological mechanisms behind radioresistance is essential in the development of therapies that are able to produce both initial and sustained response to radiotherapy. This review will investigate the different biological mechanisms utilised by PCa tumours to drive radioresistance.

Which Aspects of Psychological Resilience Moderate the Association between Deterioration in Sleep and Depression in Patients with Prostate Cancer?

This study aimed to investigate the moderating effect of psychological resilience on sleep-deterioration-related depression among patients with prostate cancer, in terms of the total score and individual symptoms. From a survey of 96 patients with prostate cancer, 55 who reported a deterioration in their sleep quality since diagnosis and treatment completed the Zung Self-Rating Depression Scale, Connor-Davidson Resilience Scale, and the Insomnia Severity Index. Moderation analysis was conducted for the scale total scores and for the 'core' symptoms of each scale within this sample, based on data analysis. Interaction analysis was used to identify key associations. The moderation analysis suggested that psychological resilience moderated the depressive effect of sleep deterioration that patients reported occurred after their diagnosis and treatment and did so at the total and 'core' symptom levels of being able to see the humorous side of things and to think clearly when under pressure, but there was an interaction between this moderating effect, the strength of psychological resilience, and severity of sleep deterioration. Although it appears to be a successful moderator of depression arising from sleep deterioration that was reported by patients with prostate cancer, the effectiveness of psychological resilience is conditional upon the severity of patients' sleep difficulties and the strength of their psychological resilience. Implications for the application of resilience training and concomitant therapies for patients with prostate cancer with sleep difficulties and depression are discussed.

Industry-Led Standards, Relational Contracts and Good Faith: Are the UK and Australia Setting the Pace in (Construction) Contract Law?

The law of contract is changing. "Good faith" and "relational contracts" are used by parties more than ever before in commercial disputes. Yet, their definition and what it really means to act in good faith are still unsettled in the UK and Australia, reducing the (judicial and doctrinal) utility and impact of such conceptual tools. In contrast, the construction industry is trying to move forward in policy terms. Over the last 30 years, industry-led initiatives have been working to improve collaboration. In the UK and Australia, new collaborative frameworks contain express provisions asking parties to act with mutual trust and cooperation among other collaborative schemes. Examination of the judicial approach and industry initiatives demonstrates that there is - underpinning both - a project-centric approach (even if that is yet to be fully recognised or articulated). It is the aim of this paper to further articulate this understanding by examining at the judicial and industry positions in the UK and Australia.

Preliminary efficacy and safety analysis: 12-month results in 83 patients using a novel approach of widefield radiation therapy for extensive skin field cancerization with or without keratinocyte cancers.

PURPOSE: Evaluate the use of widefield radiation therapy (RT) in the management of extensive skin field cancerization (ESFC) with/without keratinocyte cancer (KC). METHODS: The National Dermatology Radiation Oncology Registry is a multidisciplinary collaboration (dermatologists and radiation oncologists). It captures disease description, prior therapies, radiation prescription, clinical effect, skin cosmesis scores, and toxicity data. This analysis included 12-month follow-up data on 89 treated fields from a subset of 83 patients. RESULTS: Clinical success (>90% field clearance) was 96% (ESFC, n = 63) and 88% (ESFC with KC, n = 26). Complete lesion response was seen in 96% of evaluable (n = 25) ESFC with KC. Recurrence (4/89 [5%]) and appearance of new lesions (10/89 [11%]) were minimal. Cosmetic outcome was excellent/good in 98% ESFC and 96% ESFC with KC. Grade 1-2 acute radiation dermatitis occurred in up to 80% of treated fields. The frequency of Grade 3 acute skin toxicities was low. CONCLUSIONS: Registry data demonstrate the potential for widefield RT to treat patients with significant skin pathology who have exhausted other therapies and require durable, minimally invasive treatment options. At 12 months, observed clinical success rates were higher than those reported for topical interventions for ESFC. Ongoing follow-up is required to determine longer term outcomes.

Radiotherapy, Utilizing Volumetric Modulated Arc Therapy, for Extensive Skin Field Cancerization: A Retrospective Case Series Assessing Efficacy, Safety, and Cosmetic Outcomes at 12 Months After Treatment.

Extensive Skin Field Cancerization (ESFC) describes multiple actinic keratoses, with and without keratinocyte skin cancers. These areas are characterised by dysplastic keratoses, are prone to new malignancies, involve significant morbidity, have a poor cosmetic appearance, and impact negatively on quality of life. Available topical field therapies have limited durability of efficacy. Volumetric modulated arc therapy (VMAT) is an advanced form of intensity-modulated radiotherapy which achieves highly modulated and conformal dosimetry, delivering a homogeneous dose, particularly over curved surfaces, for example, scalps and limbs. This series describes the 12-month follow-up analysis of 41 VMAT treated fields from 32 (21 M, 11 F) patients. Consent was obtained after VMAT treatment to allow access to outcomes data. Conditions treated include ESFC, Bowen's disease/SCC in situ, cutaneous squamous cell carcinoma, and basal cell carcinoma (BCC). Efficacy was measured by the percentage reduction of visible pathology within the treatment field. The primary endpoint for this review was the assessment of treatment success, defined as >90% clearance of the treatment field. As part of this definition, the appearance of isolated keratoses at 12 months was considered not significant if the field overall was clear. The development of new or recurrent cancers within the 12-month follow-up period was recorded. Thirty-six fields (87%) achieved a clinical clearance >90%. Of those, 33 (80%) fields achieved complete clearance >99% of visible actinic keratosis or keratinocyte cancers. Three fields (7%) demonstrated 91-99% clinical clearance, and no treatment failures were recorded. Two newly occurring lesions (1 BCC and 1 SCC in situ) were identified within a treated field at 12 months. The reported toxicities at 12-month post-treatment were grade 1 or 2 only, with no cases of persistent radiation dermatitis. Toxicities reported in more than 5% of cases included: alopecia (n = 4); dryness (n= 3); erythema (n = 2); and telangiectasia ulceration (n = 4). The high rate of complete clearance at 12 months seen in this case series compares very favourably with other treatments, including topical 5-fluorouracil, imiquimod, and photodynamic therapy. Toxicities reported in our patient population demonstrated that VMAT was well tolerated at 12-month post-treatment. VMAT treatment may play a growing role in future therapy for ESFC with and without keratinocyte cancers.

Prior iodine exposure and impact on thyroid function during controlled ovarian hyperstimulation: A prospective study.

AIMS: Iodine supplements are recommended for women planning pregnancy, but their impact on thyroid function during controlled ovarian hyperstimulation (COH) and into pregnancy is unknown. The aim of this study was to assess the impact of iodine supplementation on thyroid function during COH. METHODS: One-hundred and six euthyroid women (thyroid stimulating hormone (TSH) 0.4-2.5 mIU/L) planning their first COH cycle were subdivided according to iodine supplementation (nil, <6 months, ≥6 months) and compared to levothyroxine (LT4)-treated controls. Serial TSH, free thyroxine, free triiodothyronine and thyroglobulin (Tg) levels were recorded at four time points: (i) baseline, (ii) day 7 ovarian stimulation, (iii) ovulation trigger and (iv) two weeks post oocyte retrieval. Oocyte numbers, fertilisation rates and pregnancy outcome were recorded. RESULTS: TSH increased during COH for those women taking iodine supplements for ≥6 months (P = 0.025). One quarter recorded a TSH level >2.5 mIU/L before embryo transfer. A similar increase in TSH was demonstrated by LT4-dependent controls (P = 0.024) but not the remaining subgroups. Tg levels did not change during COH in any group but decreased significantly post oocyte retrieval if nil iodine (P < 0.0001) or supplemented for ≥6 months (P < 0.005). Iodine supplementation did not influence oocyte count, fertilisation or implantation rates. Women taking iodine for <6 months were four times more likely to achieve a live birth than women taking iodine for longer. CONCLUSIONS: Women taking iodine supplements for ≥6 months are less able to adapt to the thyroidal demands of COH, with responses comparable to LT4-dependent patients.

Assessment and management of newly diagnosed classical Hodgkin lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance.

The management of Hodgkin lymphoma (HL) has undergone significant changes in recent years. Due to the predilection of HL to affect younger patients, balancing cure and treatment-related morbidity is a constant source of concern for physicians and patients alike. Positron emission tomography adapted therapy has been developed for both early and advanced stage HL to try and improve the outcome of treatment, while minimising toxicities. The aim of this review is to digest the plethora of studies recently conducted and provide some clear, evidence-based practice statements to simplify the management of HL.

Phase I/II trial of concurrent extracranial palliative radiation therapy with Dabrafenib and Trametinib in metastatic BRAF V600E/K mutation-positive cutaneous Melanoma.

BACKGROUND: Concurrent treatment with BRAF inhibitors and palliative radiation therapy (RT) could be associated with increased toxicity, especially skin toxicity. Current Eastern Cooperative Oncology Group (ECOG) consensus guideline recommend ceasing BRAF inhibitors during RT. There is a lack of data regarding concurrent RT with combined BRAF and MEK inhibitors. This single-arm phase I/II trial was designed to assess the safety and tolerability of palliative RT with concurrent Dabrafenib and Trametinib in patients with BRAF-mutant metastatic melanoma. MATERIALS AND METHODS: Patients received Dabrafenib and Trametinib before and during palliative RT to soft tissue, nodal or bony metastases. The RT dose was escalated stepwise during the study period. Toxicity data including clinical photographs of the irradiated area was collected for up to 12 months following completion of RT. RESULTS: Between June 2016 to October 2019, ten patients were enrolled before the study was stopped early due to low accrual rate. Six patients were treated at level 1 (20 Gy in 5 fractions, any location) and 4 patients at level 2a (30 Gy in 10 fractions with no abdominal viscera exposed). All alive patients completed one year of post-RT follow-up. Of the 82 adverse events (AEs) documented, the majority (90%) were grade 1 and 2. Eight grade 3 events (10%) occurred in five patients, only one was treatment-related (grade 3 fever due to Dabrafenib and Trametinib). No patients experienced grade 3 or 4 RT related toxicities, including skin toxicities. One serious AE was documented in relation to a grade 3 fever due to Dabrafenib and Trametinib requiring hospitalisation. CONCLUSIONS: The lack of grade 3 and 4 RT-related toxicities in our study suggests that Dabrafenib and Trametinib may be continued concurrently during fractionated non-visceral palliative RT to extracranial sites.

A prospective study of the effect of testosterone escape on preradiotherapy prostate-specific antigen kinetics in prostate cancer patients undergoing neoadjuvant androgen deprivation therapy.

INTRODUCTION: Prostate-specific antigen (PSA) kinetic patterns during neoadjuvant androgen deprivation therapy have been shown to predict unfavorable long-term outcomes. OBJECTIVE: To investigate the effect of testosterone escape (TE) on these kinetic patterns, as this had not been previously reported. METHODS: There were 50 consecutive prostate cancer patients who received 6 months of triptorelin prior to definitive radiotherapy (RT). Testosterone and PSA levels were measured at baseline and every 6 weeks. Clinical factors were tested for their ability to predict for TE and unfavorable PSA kinetic patterns. The effects of TE, at both 1.7 and 0.7 nmol/L levels, were analyzed. RESULTS: TE occurred in at least one reading for 14% and 34% of the patients at the 1.7 and 0.7 nmol/L levels, respectively. No baseline factors predicted TE. The median PSA halving time was 25 days and the median pre-RT PSA level was 0.55 ng/mL. The only factor significantly associated with a higher pre-RT PSA level was a higher baseline PSA level. The only factor that significantly predicted a longer PSA halving time was TE at the 1.7 nmol/L level. CONCLUSIONS: TE and higher baseline PSA levels may adversely affect PSA kinetics and other outcomes for patients undergoing neoadjuvant hormone therapy prior to radiotherapy. Studies investigating the tailoring of neoadjuvant therapy by extending the duration in those patients with a higher baseline PSA level or by the addition of anti-androgens in those demonstrating TE, should be considered.

Deterioration in Sleep Quality Affects Cognitive Depression in Prostate Cancer Patients.

Men who suffer from prostate cancer (PCa) need to make important decisions regarding their treatment options. There is some evidence that these men may suffer from sleep difficulties due to their cancer or its diagnosis and treatment. Although sleep difficulties have been associated with cognitive depression in other samples of men, they have not been examined in PCa patients, despite the importance of decision-making for these men. This study was designed to investigate the association between sleep difficulties and cognitive depression in PCa patients. A sample of 96 PCa patients completed a background questionnaire, the Zung Self-Rating Depression Scale, and the Insomnia Severity Index. Comparison was made between sleep difficulty scores from before the patients received their diagnosis of PCa to the time of survey, allowing use of a "retrospective pretest" methodology. Just over 61% of the sample reported a deterioration in sleep quality, and this was significantly associated with cognitive depression (r = .346, p = .007). At the specific symptom level, having a clear mind significantly contributed to the variance in difficulty falling asleep (R2 change = .140, F for change = 9.298, p = .003). Sleeping difficulties, particularly falling asleep, are common and associated with depression-related to ability to think clearly in PCa patients. This has potentially adverse effects upon the ability of men with PCa to understand their treatment options and make decisions about them.

Quinazoline alpha-adrenoreceptor blockers as an adjunct cancer treatment: From bench to bedside.

Drug repurposing has been increasingly used by both researchers and clinicians to identify new cancer treatments. The alpha-1 adrenoreceptor blockers are a class of drugs that have been used for many years in the treatment of hypertension and benign prostatic hyperplasia. Some of the drugs in this class, notably the quinazoline derivatives, have been found to display cytotoxic properties, identifying them as potential options in the treatment of cancer. This review will examine the currently available evidence that investigates the cytotoxic and anti-cancer properties of these agents, the mechanisms behind these properties and how the alpha-1 blockers fit within current cancer therapies. It aims to answer the question of whether these agents can go from the laboratory bench top into cancer clinics.

'Steeling' effects in the association between psychological resilience and cancer treatment in prostate cancer patients.

OBJECTIVE: To test the 'buffering' effect of psychological resilience (PR) upon depression in prostate cancer patients and to also investigate any effects that past or current treatment may have had upon patients' PR as a test of the 'steeling' hypothesis of past adversity upon future resilience. METHODS: A total of 576 volunteer prostate cancer patients completed questionnaires about their demographic and treatment variables, and their psychological resilience and depression. Factor analysis was used to identify the underlying components of the resilience measure. RESULTS: PR was confirmed as an inverse correlate of depression in these men. Additionally, some past and current treatments were found to be significantly associated with patients' psychological resilience in a way suggestive of 'steeling' effects. CONCLUSION: These data provide support for the model of PR as being influenced by past experiences of adversity and demonstrate that association for prostate cancer patients.