Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1-associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.

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Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study.

A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now.

Tumor Immunology and Tumor Evolution: Intertwined Histories

The knowledge that the body possesses natural defenses to combat cancer existed long before the modern period, with multiple anecdotal reports of tumors miraculously disappearing, sometimes spontaneously or after a febrile or infectious episode. Spontaneous tumor regression of untreated malignant tumors is currently a well-accepted albeit rare phenomenon, and it is recognized that immunosuppression is associated with a higher cancer risk. The treatment of bladder carcinoma by intravesical administration of live attenuated Bacillus CalmetteGuérin bacteria was shown to be very effective in 1976 and is now standard treatment. Effective immunity against cancer involves complex interactions between the tumor, the host, and the environment. Cancer immunotherapy uses various strategies to augment tumor immunity and represents a paradigm shift in treating cancer, since attention has become more focused on the “biologic passport” of the individual tumor rather than the site of origin of the tumor. The different types of cancer immunotherapies discussed here include biologic modifiers, such as cytokines and vaccines, adoptive cell therapies, oncolytic viruses, and antibodies against immune checkpoint inhibitors, such as the co-inhibitory T-cell receptor PD-1 and one of its ligands, programmed death-ligand 1.

/pdf/cancer-immunotherapy-a-brief-review-of-the-history-2l78wia76r.pdf

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

In recent years, a lot of scientific interest has focused on cancer immunotherapy. Although chronic inflammation has been described as one of the hallmarks of cancer, acute inflammation can actually trigger the immune system to fight diseases, including cancer. Toll-like receptor (TLR) ligands have long been used as adjuvants for traditional vaccines and it seems they may also play a role enhancing efficiency of tumor immunotherapy. The aim of this perspective is to discuss the effects of TLR stimulation in cancer, expression of various TLRs in different types of tumors, and finally the role of TLRs in anti-cancer immunity and tumor rejection.

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The Role of TLRs in Anti-cancer Immunity and Tumor Rejection.

It is nearly 40 years since Bacillus Calmette-Guerin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear.

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Immunotherapy for bladder cancer.

Objectives
To evaluate the use of post-discharge venous thromboembolism (VTE) prophylaxis in UK pelvic cancer centres consistent with national guidelines.

Methods
Data was collected from healthcare professionals from 64 UK pelvic cancer centres.

Results
After radical cystectomy (RC), all cancer centres routinely use low-molecular-weight heparin (LMWH) in the perioperative period. After RC 67% of cancer centres use post-discharge LMWH routinely. After radical prostatectomy (RP), 98% of units use perioperative LMWH VTE prophylaxis routinely. After RP, 61% of hospitals always use post-discharge LMWH. In all, 27% of all UK cancer centres reported deaths or serious VTE complications from urological pelvic cancer surgery in the last 2 years.

Conclusions
The National Institute for Health and Care Excellence (NICE) issued explicit guidance of VTE prophylaxis after pelvic and abdominal cancer surgery. Conversion of national guidance into local policy is ≈60% for UK pelvic cancer centres. A lack of good quality evidence is cited as a reason for not adhering to NICE guidance.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bju.12693

Venous thromboembolism (VTE) prophylaxis and urological pelvic cancer surgery: a UK national audit.

This qualitative, focus-group study explores what patients understand about the multidisciplinary team (MDT) in cancer care. Participants were positive towards MDT working, and by strengthening the role of nurses in MDT decision-making, the representation of patients' interests can be improved.

Cancer patients' perspectives on multidisciplinary team working: an exploratory focus group study.

Multidisciplinary teams (MDTs) are increasingly the preferred method of cancer care in many specialties, including urology. MDTs provide a means of improving communication between health care professionals and patients and provide co-ordinated and timely care. As MDTs have developed, so too has the role of the specialist cancer nurse, though the concept of the clinical nurse specialist (CNS), or their involvement in the MDT are not globally universal. There is increasing evidence that the presence of the CNS in the MDT improves patient satisfaction and team effectiveness. The MDT meeting is the focal point for decision-making about patients’ care, but the roles of health care professionals in the MDT meeting are variable and poorly defined. In this paper, we examine the evidence for the role of the CNS in the urology MDT meeting, which includes communicating with colleagues and patients, co-ordinating care, as well as facilitating research and clinical governance. We discuss the challenges faced by CNSs and how their role in MDT meetings can be strengthened to enhance their effectiveness in the MDT in general.

The role of the urology clinical nurse specialist in the multidisciplinary team meeting

In the United Kingdom, our Health Needs Assessment survey return rate of 42% identified unmet needs in subjects with prostate cancer. Subjects reported the greatest unmet need was related to erectile dysfunction. Other unmet needs were related to incontinence, tiredness, hot flashes, lower urinary tract symptoms, rectal bleeding, and relationship issues.

Paula Allchorne

Papers

Immunotherapy for bladder cancer.

Venous thromboembolism (VTE) prophylaxis and urological pelvic cancer surgery: a UK national audit.

Cancer patients' perspectives on multidisciplinary team working: an exploratory focus group study.

The role of the urology clinical nurse specialist in the multidisciplinary team meeting

Identifying Unmet Care Needs of Patients with Prostate Cancer To Assist with Their Success in Coping.