Virtual HDR Boost for Prostate Cancer: Rebooting a Classic Treatment Using Modern Tech.

Prostate cancer (PC) is the most common malignancy in men. Internal radiotherapy (brachytherapy) has been used to treat PC successfully for over a century. In particular, there is level-one evidence of the benefits of using brachytherapy to escalate the dose of radiotherapy compared with standard external beam radiotherapy approaches. However, the use of PC brachytherapy is declining, despite strong evidence for its improved cancer outcomes. A method using external beam radiotherapy known as virtual high-dose-rate brachytherapy boost (vHDRB) aims to noninvasively mimic a brachytherapy boost radiation dose plan. In this review, we consider the evidence supporting brachytherapy boosts for PC and the continuing evolution of vHDRB approaches, culminating in the current generation of clinical trials, which will help define the role of this emerging modality.

Outcomes of poorly differentiated and plasmacytoid variant bladder urothelial carcinoma.

Objectives: The aim of this study is to assess the course and management of poorly differentiated bladder urothelial carcinoma (UC), including plasmacytoid UC (PUC), in our local area. Although bladder cancer is relatively common, PUC is a rare and aggressive subtype with a poor prognosis that is still poorly understood. Materials and Methods: A retrospective assessment of all poorly differentiated high-grade UC over the last 15 years (2005-2020) in the Hunter New England area was completed. In total, 37 patients were included, and PUC variant was compared with the remaining poorly differentiated UC. Results: Of the included cases, eight were PUC, nine squamous variant, two neuroendocrine, and one sarcomatoid. Overall, 23 cases proceeded to cystectomy, 15 had chemotherapy (six neoadjuvant), and 11 had radiation therapy. In the PUC subgroup, three had metastatic disease at diagnosis (37.5%). Of the three PUC patients who underwent cystectomy, all were upstaged. Two PUC cases had adjuvant chemotherapy, and one case had radiation. Within the follow-up period, the PUC group had a cause-specific mortality of 50% with a mean survival in these patients of 202 days, compared with 37.9% cause-specific mortality with survival of 671.55 days (p = 0.23) in all other undifferentiated UC cases; 5-year cause-specific mortality with Kaplan-Meier analysis was estimated at 26% compared with 59%, respectively (p = 0.058). Conclusion: Poorly differentiated UC is demonstrated to have a poor prognosis with a high mortality rate, particularly when PUC is present. Given the rarity of these variants, further studies are necessary to explore the impact of current treatment options.

Don't be fooled by the fat: A rare case of renal cell carcinoma with intratumoural fat.

Angiomyolipoma (AML) is a benign renal tumour composed of fat, smooth muscle and blood vessels. Radiologic evidence of macroscopic fat within a solid renal lesion on computed tomography was historically thought to be pathognomonic for this condition. Herein, we report a case of an incidental solid renal cell mass with multiple foci of intra-tumoral fat, which was shown to be a clear cell renal cell carcinoma (RCC) at nephrectomy. Macroscopic fat within solid renal lesions does not exclude malignancy, evaluation of other radiologic features is necessary when RCC is suspected.

Don't be fooled by the fat: A rare case of renal cell carcinoma with intratumoural fat.

Angiomyolipoma (AML) is a benign renal tumour composed of fat, smooth muscle and blood vessels. Radiologic evidence of macroscopic fat within a solid renal lesion on computed tomography was historically thought to be pathognomonic for this condition. Herein, we report a case of an incidental solid renal cell mass with multiple foci of intra-tumoral fat, which was shown to be a clear cell renal cell carcinoma (RCC) at nephrectomy. Macroscopic fat within solid renal lesions does not exclude malignancy, evaluation of other radiologic features is necessary when RCC is suspected.

TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality. METHODS AND ANALYSIS: Eligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial. ETHICS AND DISSEMINATION: NINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study. TRIAL REGISTRATION NUMBER: ANZCTN 12615000223538.

A clinician-centred programme for behaviour change in the optimal use of staging investigations for newly diagnosed prostate cancer.

OBJECTIVES: To improve imaging utilisation and reduce the widespread overuse of staging investigations, in the form of computed tomography (CT) and whole-body bone scans for men with newly diagnosed prostate cancer in the Hunter region of NSW, Australia, by implementation of a multifaceted clinician-centred behaviour change programme. PATIENTS AND METHODS: Records of all patients with a new diagnosis of prostate cancer were reviewed prior to the intervention (July 2014 to July 2015), and the results of this audit were presented to participating urologists by a clinical champion. Urologists then underwent focused education based on current guidelines. Patterns of imaging use for staging were then re-evaluated (November 2015 to July 2016). Patients were stratified into low-, intermediate- and high-risk groups as described by the D'Amico classification system. RESULTS: A total of 144 patients were retrospectively enrolled into the study cohort. The use of diagnostic imaging for staging purposes significantly decreased in men with low- and intermediate-risk disease post intervention. In low-risk patients, the use of CT decreased from 43% to 0% (P = 0.01). A total of 21% of patients underwent bone scans in the pre-intervention group compared with18% in the post-intervention group (P = 0.84). In intermediate-risk patients, the use of CT decreased from 89% to 34% (P < 0.001), whilst the use of bone scan decreased from 63% to 37% (P = 0.02). In high-risk patients, the appropriate use of imaging was maintained, with CT performed in 87% compared with 85% and bone scan in 87% compared with 65% (P = 0.07). CONCLUSION: Our results show that a focused, clinician-centred education programme can lead to improved guideline adherence at a regional level. The assessment of trends and application of such a programme at a state-based or national level could be further assessed in the future with the help of registry data. This will be particularly important in future with the advent of advanced imaging, such as prostate-specific membrane antigen positron-emission tomography.

Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography for Prostate Cancer: Distribution of Disease and Implications for Radiation Therapy Planning.

PURPOSE: To explore the prostate-specific membrane antigen (PSMA)-avid distribution of prostate cancer (PC) on positron emission tomography (PET), both at the time of initial diagnosis and at the time of relapse after definitive local treatment. METHODS AND MATERIALS: A total of 179 PSMA PET scans in patients with nil or ≤3 lesions on conventional imaging were retrospectively categorized into 3 subgroups: group A, high-risk PC with no prior definitive therapy (n=34); group B, prior prostatectomy (n=75); and group C, prior radiation therapy (n=70). The numbers and locations of the PSMA-avid lesions were mapped. The PSMA-positive lesions were identified subjectively by a nuclear medicine physician on the basis of clinical experience and taking into account the recent literature and artefacts. RESULTS: A total of 893 PSMA-avid lesions were identified; at least 1 lesion was detected in 80% of all scans. A high detection rate was present even at very low serum PSA levels (eg, at PSA ≤0.20 ng/mL in group B, the detection rate was 46%). Thirty-eight percent of studies revealed extrapelvic disease (41%, 31%, and 46% in groups A, B, and C, respectively). Almost one-third of all studies showed only oligometastases (24%, 36%, and 31% in groups A, B, and C, respectively). A large proportion of these (40%) were a solitary lesion. CONCLUSIONS: Prostate-specific membrane antigen PET demonstrated a large number of otherwise unknown metastatic lesions. Therefore we recommend PSMA PET for more accurate assessment of disease burden in initial staging of high-risk PC, as well as for restaging in patients with prostate-specific antigen relapse after primary therapies. Furthermore, a high proportion of oligometastases on PSMA PET provides a prime opportunity to investigate the role of targeted local therapies for oligometastatic PCs.

Wellbeing during Active Surveillance for localised prostate cancer: a systematic review of psychological morbidity and quality of life.

BACKGROUND: Active Surveillance (AS) is recommended for the treatment of localised prostate cancer; however this option may be under-used, at least in part because of expectations of psychological adverse events in those offered or accepting AS. OBJECTIVE: (1) Determine the impact on psychological wellbeing when treated with AS (non-comparative studies). (2) Compare AS with active treatments for the impact on psychological wellbeing (comparative studies). METHOD: We used the PRISMA guidelines and searched Medline, PsychInfo, EMBASE, CINHAL, Web of Science, Cochrane Library and Scopus for articles published January 2000-2014. Eligible studies reported original quantitative data on any measures of psychological wellbeing. RESULTS: We identified 34 eligible articles (n=12,497 individuals); 24 observational, eight RCTs, and two other interventional studies. Studies came from North America (16), Europe (14) Australia (3) and North America/Europe (1). A minority (5/34) were rated as high quality. Most (26/34) used validated instruments, whilst a substantial minority (14/34) used watchful waiting or no active treatment rather than Active Surveillance. There was modest evidence of no adverse impact on psychological wellbeing associated with Active Surveillance; and no differences in psychological wellbeing compared to active treatments. CONCLUSION: Patients can be informed that Active Surveillance involves no greater threat to their psychological wellbeing as part of the informed consent process, and clinicians need not limit access to Active Surveillance based on an expectation of adverse impacts on psychological wellbeing.

Overactive bladder syndrome - management and treatment options.

BACKGROUND: Overactive bladder syndrome is a symptom-based clinical diagnosis. It is characterised by urinary urgency, frequency and nocturia, with or without urge urinary incontinence. These symptoms can often be managed in the primary care setting. OBJECTIVE: This article provides a review on overactive bladder syndrome and provides advice on management for the general practitioner. DISCUSSION: Overactive bladder syndrome can have a significant effect on quality of life, and affects 12-17% of the population. Prevalence increases with age. The management of overactive bladder syndrome involves exclusion of underlying pathology. First line treatment includes lifestyle interventions, pelvic floor exercises, bladder training and antimuscarinic agents. Failure of conservative management necessitates urology referral. Second line therapies are more invasive, and include botulinum toxin, neuromodulation or surgical interventions such as augmentation cystoplasty or urinary diversion.

Erectile dysfunction - when tablets don't work.

BACKGROUND: Erectile dysfunction (ED) is a common clinical problem managed in the general practice setting. While the majority of men will find phosphodiesterase-5 (PDE-5) inhibitors effective, there is a subgroup of men who require second and third line therapies. OBJECTIVE: This article provides an overview of ED and its management with particular focus on the group of patients in whom oral agents fail. DISCUSSION: Erectile dysfunction is a multifactorial condition that affects approximately 40% of Australian men. The incidence of ED is age related however, it shares common risk factors with cardiovascular disease and metabolic disorders. The management of ED should begin with an assessment of cardiovascular risk factors, advice on lifestyle modification, and a trial of PDE-5 inhibitors. Second line therapies include intracavernosal injections and vacuum erection devices, while third line therapy entails penile implants. Factors that influence treatment success include partner inclusion, good patient selection, as well as ongoing support and education.

Osteoporosis from androgen deprivation therapy in prostate cancer treatment.

BACKGROUND: Bone complications from metastatic disease in prostate cancer have been well documented. Osteoporosis from androgen deprivation therapy (ADT) can further impair quality of life in this already susceptible age group. OBJECTIVE: We aimed to assess the intermediate and long term effects of ADT on bone density and the development of osteoporosis in men with prostatic cancer, and outline some practical assessment, management and treatment options. DISCUSSION: Osteoporosis, exacerbated by the use of ADT, reduces both the survival and quality of life of men who may otherwise live for many years with their well controlled prostate cancer. Hence, both preventive and treatment options should be explored and tailored to the individual, including lifestyle modifications (exercise, smoking cessation), vitamin D and calcium supplementation, and the use of bisphosphonates.

Massive immature mediastinal teratoma extending into the left pleural cavity.

We report a case of a massive mediastinal teratoma in an 18-year-old woman who presented with a short history of exertional dyspnoea. The tumor arose from the left lobe of the thymus and extended into the left pleural cavity, completely compressing the left lung and extensively shifting the mediastinum to the right. Measuring 23 cm x 17 cm x 9 cm and weighing 2005 g it is one of the largest anterior mediastinal teratomas reported. It was successfully treated by surgical resection, with a final pathological diagnosis of a grades 1-2 immature teratoma.