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PURPOSE: We identified (1) differences in localized prostate cancer (PCa) risk group at presentation and (2) disparities in access to initial treatment for Asian American, Native Hawaiian, and Pacific Islander (AANHPI) men with PCa after controlling for sociodemographic factors. METHODS: We assessed all patients in the National Cancer Database with localized PCa with low-, intermediate-, and high-risk disease who identified as Thai, White, Asian Indian, Chinese, Vietnamese, Korean, Japanese, Filipino, Hawaiian, Pacific Islander, Laotian, Pakistani, Kampuchean, and Hmong. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment or active surveillance with intermediate- or high-risk disease, adjusting for sociodemographic and clinical factors. RESULTS: Among 980,889 men (median age 66 years), all AANHPI subgroups with the exception of Thai (AOR = 0.84 [95% CI, 0.58 to 1.21], P > .05), Asian Indian (AOR = 1.12 [95% CI, 1.00 to 1.25], P > .05), and Pakistani (AOR = 1.34 [95% CI, 0.98 to 1.83], P > .05) men had greater odds of presenting at a progressively higher PCa risk group compared with White patients (Chinese AOR = 1.18 [95% CI, 1.11 to 1.25], P < .001; Japanese AOR = 1.36 [95% CI, 1.26 to 1.47], P < .001; Filipino AOR = 1.37 [95% CI, 1.29 to 1.46], P < .001; Korean AOR = 1.32 [95% CI, 1.18 to 1.48], P < .001; Vietnamese AOR = 1.20 [95% CI, 1.07 to 1.35], P = .002; Laotian AOR = 1.60 [95% CI, 1.08 to 2.36], P = .018; Hmong AOR = 4.07 [95% CI, 1.54 to 10.81], P = .005; Kampuchean AOR = 1.55 [95% CI, 1.03 to 2.34], P = .036; Asian Indian or Pakistani AOR = 1.15 [95% CI, 1.07 to 1.24], P < .001; Native Hawaiians AOR = 1.58 [95% CI, 1.38 to 1.80], P < .001; and Pacific Islanders AOR = 1.58 [95% CI, 1.37 to 1.82], P < .001). Additionally, Japanese Americans (AOR = 1.46 [95% CI, 1.09 to 1.97], P = .013) were more likely to receive treatment compared with White patients. CONCLUSION: Our findings suggest that there are differences in PCa risk group at presentation by race or ethnicity among Asian American, Native Hawaiian, and Pacific Islander subgroups and that there exist disparities in treatment patterns. Although AANHPI are often studied as a homogenous group, heterogeneity upon subgroup disaggregation underscores the importance of further study to assess and address barriers to PCa care.

BACKGROUND Prostate cancer in black men is associated with poorer outcomes than their white counterparts. However, most studies reporting this disparity were conducted in localized prostate cancer and primarily in the United States. METHODS Data regarding prostate cancer incidence and mortality for East London between 2008 and 2010 were obtained from the UK National Disease Registration Service. We further evaluated survival outcomes of 425 cases of mCRPC in St Bartholomew's Hospital, East London, between 1997 and 2016, and analyzed whether ethnicity impacted on responses to different treatment types. RESULTS The incidence of prostate cancer in black men was higher than white men in East London. Prostate cancer-specific mortality was proportional to incidence based on ethnic groups. In the detailed analysis of 425 patients, 103 patients (24%) were black (B), and the remainder white (W). Baseline characteristics were comparable in both groups, although black patients had a lower baseline hemoglobin (p

Aim This narrative review aims to describe established and emerging urinary biomarkers in the diagnosis and surveillance of non-muscle invasive bladder cancer. It provides a comprehensive account of classical, FDA-approved protein biomarkers and discusses their limitations. Further, we discuss the role that epigenetic, genetic, and exosomal markers can play to enhance sensitivity and specificity of the available tests. Background The initial diagnosis and surveillance of bladder cancer involves a combination of cystoscopy, upper urinary tract imaging, and urine cytology. Despite high specificity, cytology is limited by low sensitivity. There are currently 6 urinary assays approved by the FDA to enhance diagnosis and surveillance of bladder cancer. While these have improved diagnosis and surveillance when combined with cytology, these tests are still not sufficiently sensitive and false positives often occur in benign conditions which result in inflammation of the urinary tract. Advancements in laboratory techniques have produced significant advancements in epigenetic and genetic markers, as well as extracellular vesicles, with DNA- and RNA-based markers dominating the research in this area in recent years. Methods We identified relevant published data, using the PubMed/ Medline search engines as well as Google Scholar. We performed an online search using the terms “bladder cancer”, “non-muscle invasive bladder cancer” in combination with “urine biomarkers” and limited articles in English published up to February 2020. This review consolidated on all available narrative and systematic reviews published in the 5 years in this field, while also reviewing the original data of each clinical trial or observational study which led to the development of the biomarkers. Conclusion The development of laboratory techniques and understanding urine-based biomarkers in BC has fuelled the use of noninvasive liquid-based biomarkers to complement urine cytology. Nonetheless, none are sufficiently effective when used in isolation, and cytology remains the gold standard in many practices. Future efforts will be focused on using these markers in combination as a predictive signature, and moving on to validating them for use in everyday clinical practice.

This article is co-authored by a patient with metastatic hormone-sensitive prostate cancer who is receiving abiraterone and androgen deprivation therapy treatment in Manchester, UK. The patient relates his personal experiences struggling with the diagnosis, his experience with treatment and the physical, emotional and psychosexual impact on his life. After his diagnosis, the patient has become an outspoken advocate and fundraiser for prostate cancer awareness and wants to ensure that novel treatments with proven efficacy and tolerability, such as abiraterone, are available for all men in his condition. The specialist nursing and physician perspectives, provided by healthcare professionals based in London who are not directly involved in this patient’s care, were written in response to the challenges and concerns highlighted by this patient. The role of the specialist nurse as a key healthcare professional in the cancer patient journey, particularly in managing the complex physical and emotional side effects of treatment, is highlighted in this perspective piece. The physician reviews the current difficulties of establishing an effective screening programme in prostate cancer, the common side effects of hormone treatment and the significant progress and challenges in novel drug development and prescription in metastatic hormone-sensitive prostate cancer. While written primarily from the perspective of a patient and healthcare professionals in England, many messages in this commentary would resonate with patients and professionals involved in the care of prostate cancer worldwide.

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has changed radically in recent years. Androgen deprivation therapy (ADT) alone was for decades the standard of care for treating mHSPC. This changed when studies showed that the addition of docetaxel chemotherapy or abiraterone acetate to ADT significantly increases overall survival of patients with mHSPC, followed by more recent evidence showing the efficacy of androgen receptor antagonists, such as enzalutamide and apalutamide, in this setting. While this rapid therapeutic evolution is welcome, it presents clinicians with a crucial challenge: the choice of treatment selection and sequencing. In the first-line setting there are no comparative data currently available to guide treatment choice between the different available regimens, and no prospective data to guide clinical decision after progression. Decisions on treatment will now need to be personalised based on indirect comparison of the available efficacy data from multiple phase 3 studies, together with considerations of disease volume, comorbidities, treatment aims, toxicity profile and cost reimbursement within the healthcare setting. Here, we provide an overview of the clinical trial data to date and propose some biological and clinical insights which may be helpful in making decisions on treatment selection and sequencing.

Radiation therapy is an essential component of cancer care, contributing up to 40% of curative cancer treatment regimens. It creates DNA double-strand breaks causing cell death in highly replicating tumour cells. However, tumours can develop acquired resistance to therapy. The efficiency of radiation treatment has been increased by means of combining it with other approaches such as chemotherapy, molecule-targeted therapies and, in recent years, immunotherapy (IT). Cancer-cell apoptosis after radiation treatment causes an immunological reaction that contributes to eradicating the tumour via antigen presentation and subsequent T-cell activation. By contrast, radiotherapy also contributes to the formation of an immunosuppressive environment that hinders the efficacy of the therapy. Innate immune cells from myeloid and lymphoid origin show a very active role in both acquired resistance and antitumourigenic mechanisms. Therefore, many efforts are being made in order to reach a better understanding of the innate immunity reactions after radiation therapy (RT) and the design of new combinatorial IT strategies focused in these particular populations.

Niraparib is an oral, potent, highly selective poly-ADP ribose polymerase 1 (PARP1) and PARP2 inhibitor. In most developed countries, it is approved as a maintenance treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with complete or partial response to platinum-based therapy. These approvals are based on results of randomised, double-blind, placebo-controlled trials, particularly the NOVA trial and more recently the PRIMA trial. In this comprehensive review, we delve into the scientific basis of PARP inhibition, discussing both preclinical and clinical data which have led to the current approval status of niraparib. We also discuss ongoing trials and biological rationale of combination treatments involving niraparib, with particular focus on antiangiogenic drugs, immune checkpoint inhibitors and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS/STING) pathway. In addition, we reflect on potential strategies and challenges of utilising current biomarkers for treatment selection of patients to ensure maximal benefit.

BackgroundAdvanced Head and Neck Squamous Cell Cancer (HNSCC) is associated with a poor prognosis, and biomarkers that predict response to treatment are highly desirable. The primary aim was to predict Progression Free Survival (PFS) with a multivariate risk prediction model.MethodsBlood samples from 56 HNSCC patients were prospectively obtained within a Phase 2 clinical trial (NCT02633800), before and after the first treatment cycle of platinum-based chemotherapy, to identify biological covariates predictive of outcome. A total of 42 baseline covariates were derived pre-treatment, which were combined with 29 covariates after one cycle of treatment. These covariates were ranked and selected by Bayesian multivariate regression to form risk scores to predict PFS, producing “baseline” and “combined” risk prediction models respectively.ResultsThe baseline model comprised of CD33+CD14+ monocytes, Double Negative B cells and age, in a weighted risk signature which predicted PFS with a concordance index (C-index) of 0.661. The combined model composed of baseline CD33+CD14+ monocytes, baseline Tregs, after-treatment changes in CD8 effector memory T cells, CD8 Central memory T cells and CD3 T Cells, along with the hypopharyngeal primary tumor subsite. This weighted risk signature exhibited an improved C-index of 0.757. There was concordance between levels of CD33+CD14+ myeloid cells in tumor tissue, as demonstrated by imaging mass cytometry, and peripheral blood in the same patients. This monocyte subpopulation also had univariate predictive value (log-rank p value = 0.03) but the C-index was inferior to the combined signature.ConclusionsThis immune-based combined multimodality signature, obtained through longitudinal peripheral blood monitoring, presents a novel means of predicting response early on during the treatment course.FundingDaiichi Sankyo Inc, Cancer Research UK, EU IMI2 IMMUCAN, UK Medical Research Council, European Research Council (335326), National Institute for Health Research and The Institute of Cancer Research.

Tertiary lymphoid structures (TLSs) develop in non-lymphatic tissue in chronic inflammation and cancer. TLS can mature to lymph node (LN) like structures with germinal centers and associated vasculature. TLS neogenesis in cancer is highly varied and tissue dependent. The role of TLS in adaptive antitumor immunity is of great interest. However, data also show that TLS can play a role in cancer metastasis. The importance of lymphatics in cancer distant metastasis is clear yet the precise detail of how various immunosurveillance mechanisms interplay within TLS and/or draining LN is still under investigation. As part of the tumor lymphatics, TLS vasculature can provide alternative routes for the establishment of the pre-metastatic niche and cancer dissemination. The nature of the cytokine and chemokine signature at the heart of TLS induction can be key in determining the success of antitumor immunity or in promoting cancer invasiveness. Understanding the biochemical and biomechanical factors underlying TLS formation and the resulting impact on the primary tumor will be key in deciphering cancer metastasis and in the development of the next generation of cancer immunotherapeutics.

Aim: This is a narrative review with an aim to summarise and describe urinary biomarkers in the surveillance of non-muscle-invasive bladder cancer (NMIBC). It provides a summary of FDA-approved protein biomarkers along with emerging ones which utilise genetic, epigenetic and exosomal markers. We discuss the current limitations of the available assays.Background: Current guidelines advice a combination of cystoscopy, imaging,and urine cytology in diagnosis and surveillance. Although cytology has a high specificity, it is limited by low sensitivity particularly in low grade tumours. There are six FDA-approved urinary assays for diagnosis and surveillance of bladder cancer. They have shown to improve sensitivity and specificity to be used alongside cytology and cystoscopy but have a lower specificity in comparison to cytology and false positives often occur in benign conditions. Recent developments in laboratory techniques has allowed for use of markers which are RNA-, DNA-based as well as extracellular vesicles in the past decade.Methods: Using the PubMed/Medline search engines as well as Google Scholar, we performed an online search using the terms “bladder cancer,” “non-muscle invasive bladder cancer,” and “urine biomarkers” with filter for articles in English published up to May 2021. Systematic reviews and original data of clinical trials or observational studies which contributed to the development of the biomarkers were collated.Results: Biomarkers identified were divided into FDA-approved molecular biomarkers, protein biomarkers and gene-related biomarker with a table summarising the findings of each marker with the most relevant studies. The studies conducted were mainly retrospective. Due to the early stages of development, only a few prospective studies have been done for more recently developed biomarkers and limited meta-analyses are available.Therefore a detailed evaluation of these markers are still required to decide on their clinical use.Conclusion: Advancements of analytical methods in BC has driven the research towards non-invasive liquid-based biomarkers in adjunct to urine cytology. Further large prospective studies are required to determine its feasibility in a clinical setting as they are not effective when used in isolation as they have their limitation. With the ongoing pandemic, other than reduction in costs and increased accuracy, the need for biomarkers to cope with delay in cystoscopies in diagnosis and surveillance is crucial. Thus clinical trials with direct comparison is required to improve patient care.

Diffuse glioma is the most common primary tumor of the central nervous system. The prognosis of the individual tumor is heavily dependent on its grade and subtype. Homeobox B7 (HOXB7), a member of the homeobox family, is abnormally overexpressed in a variety of tumors. However, its function in glioma is unclear. In this study, HOXB7 mRNA and protein expression levels were analyzed in 401 gliomas from the CGGA RNA-seq database (325 cases) and our hospital (76 cases). HOXB7 expression, at both mRNA and protein levels, were upregulated in glioblastoma (GBM) and isocitrate dehydrogenase 1 (IDH1) wild-type glioma tissues. Kaplan–Meier with log-rank test showed that patients with high HOXB7 expression had a poor prognosis (p < 0.0001). Moreover, HOXB7 protein was deleted in 90.9% (20/22) of oligodendrogliomas and 13.0% (3/23) of astrocytomas. The sensitivity and specificity of HOXB7 protein deletion in oligodendroglioma were 90.9% (20/22) and 87.0% (20/23), respectively. To verify the reliability of using HOXB7 in differentiating oligodendroglioma, we used 1p/19q fluorescence in situ hybridization (FISH) testing as a positive control. The Cohen’s kappa coefficient of HOXB7 immunohistochemistry staining and 1p/19q FISH testing was 0.778 (95% CI: 0.594–0.962, p < 0.001). In conclusion, HOXB7 is an independent predictor of poor prognosis in all grade gliomas. Additionally, HOXB7 is also a highly sensitive and specific indicator to differentiate oligodendroglioma from astrocytoma.

The COVID-19 pandemic has resulted in a substantial increase in waiting times for cystoscopies, prompting concerns of delayed diagnoses and substandard surveillance of bladder cancer. Expanding the role of urinary biomarkers in diagnostic and surveillance pathways could be a strategy to address this problem, and several novel biomarkers have shown promise for this purpose.

BACKGROUND: Bleomycin, Etoposide and Cisplatin (BEP) chemotherapy is the conventional treatment regimen for patients with germ cell tumours. The regimen is highly emetogenic and immunosuppressive. High dose steroids are often prescribed with this regimen as antiemetic prophylaxis but may have adverse effects in the context of immunosuppression. OBJECTIVE: To investigate whether the use of a steroid-sparing antiemetic protocol (substituting dexamethasone with olanzapine) affects the incidence of neutropenia and associated hospital admissions in patients receiving BEP chemotherapy. DESIGN, SETTING, PARTICIPANTS AND STATISTICAL ANALYSIS: Records from 108 patients who received BEP in St Bartholomew's Hospital, London were divided into two groups by antiemetic regimen. Group 1 (treated 2008-2013) were treated with a steroid-containing antiemetic protocol and Group 2 (treated 2014-2017) were given a steroid-sparing protocol, i.e. using olanzapine. Outcomes include incidence of neutropenia at nadir blood count, severity of neutropenia, hospital admissions due to febrile neutropenia (FN) and baseline risk factors associated with FN. Statistical analyses were performed using two-sided Chi-squared tests. RESULTS AND LIMITATIONS: Baseline characteristics were balanced in age, gender, histology, and proportion of IGCCCG poor-risk patients. The incidence of neutropenia of any grade (Group 1, 96.2%, Group 2, 98.1%) was comparable although Group 2 had more patients with severe neutropenia (77.7%, G1 vs 88.8%, G2). There was a significant difference in FN Incidence (22%, G1 vs 7.5%, in G2, p=0.030). Most cases of FN occurred in Cycle 1. Two baseline characteristics were over-represented in patients who developed FN - females and patients ≥ 50 years old. CONCLUSION: By comparing two cohorts who received prophylactic antibiotics, our audit suggests that rates of febrile neutropenia related admissions have decreased in the cohort of patients that we employed a steroid-sparing antiemetic protocol.

Cancer-specific survival rates in patients with learning difficulties (LD) are poorer than the general population. Issues such as delayed diagnosis, compliance, consent and needs for individualised care and support requirements can make it more demanding to manage these patients in a busy clinical environment. Our case highlights a patient with learning disabilities who presented with advanced testicular cancer due to delayed detection, and the challenges needing consideration to ensure such patients receive good care. This report also highlights an example of adapting curative intent treatment to an individual with complex needs, and the importance of patient and family involvement in decision-making to ensure these vulnerable patients receive safe and effective healthcare. The practicalities of multidisciplinary team working in the context of key legislation and existing frameworks to guide practice in the management of LD patients are also discussed.

35 Background: Prostate cancer in Black (B) men has been associated with poorer outcomes than their White (W) counterparts. However, this perception has been derived from studies conducted predominantly in the localized prostate cancer setting, were based on data derived from clinical trials and usually conducted solely within the United States. Methods: We reviewed the outcomes of cases with metastatic castration resistant prostate cancer (mCRPC) treated at St Bartholomew’s Hospital – the UK's largest Healthcare Trust - between 1997-2016. Statistical analyses were conducted using Intercooled Stata 8.2 (State College, TX, USA). Results: We identified 425 cases of mCRPC in the 20 year period. A substantial minority of our patients, 103 (24%) were Black (B), and the remainder White (W). Characteristics were matched in age (73 years in both groups), proportion enrolled in clinical trials (33% in both groups) and median PSA (65.6,B vs 78,W, p=0.86), with a larger proportion of Black patients with a ECOG Performance Status ≥ 2 (19%,B vs 9%,W). In the total cohort analysis, the median Overall Survival (OS) was 25.5 months (B) vs 21.8 months (W), (Hazard Ratio, HR=0.81,p=0.08). For the subpopulation who received chemotherapy at some point of their treatment (n=306), survival was comparable in both groups (median OS 23.8 months, B vs 22.8 months, W, HR=0.97,p=0.82). Interestingly, there was a trend to prolonged survival in the Black population in those who only received hormone therapy (n=106) throughout their treatment course; 39.7 months (B) vs 17.1 months (W), HR=0.54, p=0.019. In a multivariate analysis for prognostic factors for survival from mCRPC therapy considering ethnicity (HR 0.81 p=0.08), time from diagnosis to castrate resistance (HR 1.02, p=0.136), presence of bone metastases at CRPC diagnosis (HR 1.89,p=0.001) – only bone metastases were significant. Conclusions: In the first set of real-world data in a study conducted outside the US, we demonstrate that Black patients do not do worse than White patients with mCRPC. The study suggests that there is a greater margin of benefit of hormone-based therapy in the Black subpopulation.

The treatment of poor prognosis chemotherapy naïve or relapsed testicular cancer is challenging. In poor prognosis treatment naïve disease, the outlook for patients with standard approaches utilising three weekly cisplatin based regimens, most commonly bleomycin, etoposide and cisplatin (BEP) is suboptimal, and one can expect more than half of patients to relapse or progress and need salvage treatment. Recent randomised studies have lent weight to the use of dose intensified treatments in these selected patient groups. In relapsed testicular cancer, post platinum based chemotherapy controversy exists as to the optimum relapse regimen as significant cure rates can be expected by re-treating with both conventional dose and high dose or dose intense regimens. Areas covered: This review seeks to outline the evidence for alternative approaches beyond standard three weekly cisplatin based regimens in poor risk metastatic disease. It also explores the evidence available for selection between conventional dose and high dose strategies on relapse. Expert commentary: An overview of the data is presented to support personalising therapy selection in both poor risk and relapsed metastatic germ cell tumors.

We present the case of a 34-year old woman who initially presented with obesity and back pain. She was eventually diagnosed with Cushing's syndrome secondary to an adrenocortical carcinoma that had metastasised to her spine, causing cauda equina compression. The delays in reaching the correct diagnosis caused significant morbidity and exemplify the pitfalls of premature closing, a common cognitive error in diagnostic reasoning.

The admission of critically unwell patients with cancer to the intensive care unit (ICU) often presents physicians and intensivists with a clinical and ethical dilemma. Studies in the 1990s cited ICU mortality rates of 75–91% for cancer patients who required intubation, and up to 95% in patients