Does Research from Clinical Trials in Metastatic Hormone-sensitive Prostate Cancer Treatment Translate into Access to Treatments for Patients in the "Real World"? A Systematic Review.

CONTEXT: Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical trials that demonstrated significant clinical benefits with docetaxel chemotherapy or novel hormone therapy (NHT) in addition to androgen deprivation therapy (ADT). Despite these advances, there is evidence to show that these treatments are not being utilised for mHSPC in clinical practice. OBJECTIVE: To determine the utilisation of docetaxel and NHT in mHSPC in routine practice and the determinants of variation in their use. EVIDENCE ACQUISITION: MEDLINE and Embase were searched systematically for studies on utilisation of treatments for primary mHSPC that were based on regional or national data sets and published after January 2005. Study results were summarised using a narrative synthesis. EVIDENCE SYNTHESIS: Thirteen papers were included in the analysis, six full-text articles and seven abstracts, on studies that included a total of 166 876 patients. The utilisation rate of treatment intensification with either docetaxel or NHT (enzalutamide, apalutamide, or abiraterone) in addition to ADT ranged from 9.3% to 38.1% across the studies. Younger, White patients with fewer comorbidities and living in more urban settings were more likely to be prescribed treatment intensification. Patients treated in private academic institutions by oncologists were more likely to receive docetaxel or NHT. Socioeconomic status did not impact receipt of systemic therapy. NHT utilisation rates appear to have increased over time. CONCLUSIONS: These results highlight the need to change the approach to the treatment of primary mHSPC in the real world by harnessing the practice-changing results from recent trials in this setting to optimise upfront systemic therapy for this patient population. PATIENT SUMMARY: We reviewed the use of treatments for primary metastatic hormone-sensitive prostate cancer that showed a benefit in key clinical trials. We found that these treatments are underused, particularly among certain patient groups.

What can patient-reported experience measures tell us about the variation in patients' experience of prostate cancer care? A cross-sectional study using survey data from the National Prostate Cancer Audit in England.

OBJECTIVES: A national survey aimed to measure how men with prostate cancer perceived their involvement in and decisions around their care immediately after diagnosis. This study aimed to describe any differences found by socio-demographic groups. DESIGN: Cross-sectional study of men who were diagnosed with and treated for prostate cancer. SETTING: The National Prostate Cancer Audit patient-reported experience measures (PREMs) survey in England. PARTICIPANTS: Men diagnosed in 2014-2016, with non-metastatic prostate cancer, were surveyed. Responses from 32 796 men were individually linked to records from a national clinical audit and to administrative hospital data. Age, ethnicity, deprivation and disease risk classification were used to explore variation in responses to selected questions. PRIMARY AND SECONDARY OUTCOME MEASURES: Responses to five questions from the PREMs survey: the proportion responding to the highest positive category was compared across the socio-demographic characteristics above. RESULTS: When adjusted for other factors, older men were less likely than men under the age of 60 to feel side effects had been explained in a way they could understand (men 80+: relative risk (RR)=0.92, 95% CI 0.84 to 1.00), that their views were considered (RR=0.79, 95% CI 0.73 to 0.87) or that they were involved in decisions (RR=0.92, 95% CI 0.85 to 1.00). The latter was also apparent for men who were not white (black men: RR=0.89, 95% CI 0.82 to 0.98; Asian men: RR=0.85, 95% CI 0.75 to 0.96) and, to a lesser extent, for more deprived men. CONCLUSIONS: The observed discrepancies highlight the need for more focus on initiatives to improve the experience of ethnic minority patients and those older than 60 years. The findings also argue for further validation of discriminatory instruments to help cancer care providers fully understand the variation in the experience of their patients.

Organisation and delivery of supportive services for patients with prostate cancer in the National Health Service in England and Wales: a national cross-sectional hospital survey and latent class analysis.

OBJECTIVES: We assessed how often National Health Service (NHS) hospitals reported that they had specific supportive services for patients with prostate cancer available onsite, including nursing support, sexual function and urinary continence services, psychological and genetic counselling, and oncogeriatric services. We identified groups of hospitals with similar patterns of supportive services. DESIGN/SETTING: We conducted an organisational survey in 2021 of all NHS hospitals providing prostate cancer services in England and Wales. Latent class analysis grouped hospitals with similar patterns of supportive services. RESULTS: In 138 hospitals, an advanced prostate cancer nurse was available in 125 hospitals (90.6%), 107 (77.5%) had a clinical nurse specialist (CNS) attending all clinics, 103 (75.7%) had sexual function services, 111 (81.6%) had continence services and 93 (69.4%) psychological counselling. The availability of genetic counselling (41 hospitals, 30.6%) and oncogeriatric services (15 hospitals, 11.0%) was lower. The hospitals could be divided into three groups. The first and largest group of 85 hospitals provided the most comprehensive supportive services onsite: all hospitals had a CNS attending all clinics, 84 (98.8%) sexual function services and 73 (85.9%) continence services. A key characteristic of the second group of 31 hospitals was that none had a CNS attending all clinics. A key characteristic of the third group of 22 hospitals was that none had sexual function services available. The hospitals in the largest group were more likely to run joint clinics (p<0.001) and host the regional specialist multidisciplinary team (p=0.002). CONCLUSIONS: There is considerable variation in supportive services for prostate cancer available onsite in NHS hospitals in England and Wales. Availability of genetic counselling and oncogeriatric services is low. The different patterns of supportive services among hospitals demonstrate that initiatives to improve the availability of the entire range of supportive services to all patients should be carefully targeted.

Treatment-related toxicity using prostate bed versus prostate bed and pelvic lymph node radiation therapy following radical prostatectomy: A national population-based study.

Purpose There is debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation in addition to prostate bed radiotherapy when used to treat disease recurrence following radical prostatectomy. We compared toxicity from radiation therapy (RT) to the prostate bed and pelvic lymph nodes (PBPLN-RT) with prostatebed only radiation therapy (PBO-RT) following radical prostatectomy. Methods and Materials Patients with prostate cancer who underwent post-prostatectomy RT between 2010 and 2016 were identified by using the National Prostate Cancer Audit (NPCA) database. Follow-up data was available up to December 31, 2018. Validated outcome measures, based on a framework of procedural and diagnostic codes, were used to capture ≥Grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity. An adjusted competing-risks regression analysis estimated subdistribution hazard ratios (sHR). A sHR > 1 indicated a higher incidence of toxicity with PBPLN-RT than with PBO-RT. Results 5-year cumulative incidences in the PBO-RT (n = 5,087) and PBPLNRT (n = 593) groups was 18.2% and 15.9% for GI toxicity, respectively. For GU toxicity it was 19.1% and 20.7%, respectively. There was no evidence of difference in GI or GU toxicity after adjustment between PBO-RT and PBPLN-RT (GI: adjusted sHR, 0.90, 95% CI, 0.67-1.19; P = 0.45); (GU: adjusted sHR, 1.19, 95% CI, 0.99-1.44; P = 0.09). Conclusions This national population-based study found that including PLNs in the radiation field following radical prostatectomy is not associated with a significant increase in rates of ≥Grade 2 GI or GU toxicity at 5 years.

Practicalities, challenges and solutions to delivering a national organisational survey of cancer service and processes: Lessons from the National Prostate Cancer Audit.

Organisational surveys are a critical process to assess the configuration and availability of services within health care systems. Cancer service organizational surveys enable understanding of variation in structure, processes and outcomes of cancer care according to the availability of facilities and their geographical organisation. This is critical for evaluating the delivery of cancer care services across a specified region. Furthermore, the organisational survey provides essential information about patient support services which can be used to inform patients where particular allied health services are available. The National Prostate Cancer Audit (NPCA) is an audit of all prostate cancer services in England and Wales. The NPCA encompasses all prostate cancer diagnostics, treatments (including surgery, radiotherapy and systemic therapy) and allied services. The NPCA conducted an organisational survey in 2021 via an online questionnaire sent to the prostate cancer clinical leads within each of the 138 NHS providers and we had a response rate of 93 %. There are many challenges to conducting an organisational survey and gaining a high completion rate is still difficult. The challenges that the NPCA faced included accuracy, completion, duplicates and discrepancies in responses. From this experience, we have developed some suggestions for the practical delivery and development of future organisational surveys. It was thanks to the use of many of these strategies, and the engagement of clinicians with the NPCA, that we were able to achieve such a high response rate. Despite these challenges, the importance of organisational surveys of cancer services is demonstrated by the better understanding of structure, processes and outcomes of cancer care according to the accessibility of facilities and their geographical organisation. This is essential for evaluating and improving the delivery of cancer care services across a region.

Is Clinical Research Serving the Needs of the Global Cancer Burden? An Analysis of Contemporary Global Radiation Therapy Randomized Controlled Trials.

PURPOSE: Randomized controlled trials (RCTs) are the cornerstone of delivering sustained improvements in cancer outcome. To inform radiation therapy research policy and prioritization, we analyze the radiation therapy RCT landscape including comparison with trials of systemic therapies over the same period, with a specific focus on funding and disparities across income settings. METHODS AND MATERIALS: This retrospective cohort study identified all phase 3 RCTs evaluating anticancer therapies published from 2014 to 2017. RCTs were classified according to anticancer modality and country of origin. Descriptive statistics were used to compare key characteristics of radiation therapy RCT studies according to study design characteristics, tumor types evaluated, types of intervention appraised, treatment intent and main funding sources. RESULTS: The study cohort included 694 RCTs of which 64 were radiation therapy RCTs (9%) compared with 601 systemic therapy RCTs (87%). Among all radiation therapy RCTs, 47% of them focused on 2 areas of evaluation: (1) combining radiation therapy with systemic agents (25%) and (2) changes in dose fractionation (22%). The most common cancers studied were head and neck (22%), lung (22%), and breast (14%), with cervical cancer trials representing only 3% of the cohort. Among the radiation therapy RCTs, 33% of them met their primary endpoint, and 62% assessed interventions in the curative setting compared with 31% in systemic therapy RCTs. For their country locations, 77% of radiation therapy RCTs took place in high-income countries, 13% in low-and-middle-income countries, and 11% in both high-income and low-and-middle-income countries. For funding, 17% of radiation therapy RCTs received funding from industry compared with 79% of systemic therapy RCTs. CONCLUSIONS: This study highlights the need for greater investment in radiation therapy RCTs and the need to look at the disparities in conducting RCTs globally. The study emphases the urgent need for more capacity building for cancer clinical trials in low-and-middle-income countries and more sustainable funding sources.

Real-world outcomes associated with new cancer medicines approved by the Food and Drug Administration and European Medicines Agency: A retrospective cohort study.

PURPOSE: Real-World Data (RWD) studies are increasingly used to support regulatory approvals, reimbursement decisions, and changes in clinical practice for novel cancer drugs. However, few studies have systematically appraised their quality or compared outcomes to pivotal trials. METHODS: All RWD studies (2010-2019) for drugs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) from 2010 to 2015 for solid organ tumours in the non-curative setting were identified. Quality assessment was undertaken using the Newcastle Ottawa Scale. Survival differences between each RWD study and the pivotal trial were determined using a related sample Wilcoxon signed-rank test. RESULTS: 293 RWD studies for 45 of the 57 drug indications approved by the FDA/EMA were identified. The most common tumour types were prostate cancer (29%, n = 86) and melanoma (15%, n = 43). A quarter of the studies had industry funding. No high-quality studies were identified, and 78% were low quality. Comparative survival analysis between RWD and pivotal trials was possible for 224 studies (37 drug indications). Differences in median survival between the RWD studies and their corresponding trial ranged from -32 months to 21 months (IQR -4·2 months to 1·6 months). Low-quality studies were more likely to report superior survival outcomes (23%) compared to higher quality studies (8%) (p = 0.02). CONCLUSION: RWD study quality for novel cancer drugs is low and of insufficient rigour to inform reimbursement decisions and clinical practice. RWD studies seeking publication should provide a completed quality assessment tool on submission. Greater investment in properly designed RWD studies is required.

The impact of national non-pharmaceutical interventions ('lockdowns') on the presentation of cancer patients.

One of the most ignored aspects of the COVID-19 pandemic has been the impact of public health measures by governments on wider health and welfare. From March 2020, hospitals in the UK saw a dramatic reduction in patients with cancer presenting due to multifactorial reasons. The impact of the pandemic on patients with cancer in the South East London Cancer Alliance was studied. The specific aims were (1) to examine the reduction in cancer diagnoses during the first wave of the pandemic and (2) to examine the stage of diagnosis of patients with cancer presenting during the pandemic compared with that of patients presenting before the pandemic. There was an 18.2% reduction in new cancer diagnoses (an estimate of 987 cancers), when compared with 2019. This fall in cancer diagnoses was most marked in patients with prostate (51.4%), gynaecological (29.7%), breast (29.5%) and lung (23.4%) cancers. There was an overall 3.9% increase in advanced stage presentation (Stages 3 and 4), with an overall 6.8% increase in Stage 4 cancers during this period. The greatest shifts were seen in lung (increase of 6.3%, with an 11.2% increase in Stage 4 cancer alone) and colorectal (5.4%) cancers. For prostate cancer, there was an increase in 3.8% in those presenting with Stage 4 disease. For breast cancer, there was an 8% reduction in patients diagnosed with Stage 1 cancer with commensurate increases in the proportion of those with Stage 2 disease. The experiences in cancer are a salient warning that pandemic control measures and policy need to balance all health and welfare. Alternative strategies need to be adopted during further waves of the current and any future pandemic to ensure that patients with cancer are prioritised for diagnosis and treatment to prevent late-stage presentation and an increase in avoidable deaths.

Acute Kidney Injury Biomarkers: What Do They Tell Us?

The definition of acute kidney injury (AKI) is now well established and encompasses changes in both the urine output and the serum creatinine (SCr) over time. Many studies to date have concentrated solely on the SCr criteria, as this is relatively easy to monitor, given that accurate urine output is rarely measured outside critical care areas. However, many studies have emphasised the inadequacies of SCr in highlighting potential renal injury in a timely fashion. These limitations reflect not only acute changes in creatinine metabolism in the critically ill but also the kinetics of creatinine generation that may hinder early recognition of AKI. In turn, this may prevent judicious intervention promoting the misconception that little can be done for patients with this devastating condition except treating the consequences. Such observations have led to much research focused on identifying early indicators of AKI that may enable early treatment and hopefully lead to improved outcomes. This explains in part the reasoning behind the interest in biomarkers of AKI and which may see them develop a role as part of established clinical tool(s) in both the assessment of severity of AKI and the potential to assess recovery. However, much of the effort behind biomarker research has focused on the ability of such candidate molecules to predict AKI as defined by the imperfect gold standards used currently. It may be that the presence of renal biomarkers associated with renal stress or injury in isolation dictates poor outcomes and as such may provide diagnostic certainty in their own right.