CREST: phase III study of sasanlimab and Bacillus Calmette-Guérin for patients with Bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer.

Bacillus Calmette-Guérin (BCG) is the standard of care for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). BCG in combination with programmed cell death-1 (PD-1) inhibitors may yield greater anti-tumor activity compared with either agent alone. CREST is a phase III study evaluating the efficacy and safety of the subcutaneous PD-1 inhibitor sasanlimab in combination with BCG for patients with BCG-naive high-risk NMIBC. Eligible participants are randomized to receive sasanlimab plus BCG (induction ± maintenance) or BCG alone for up to 25 cycles within 12 weeks of TURBT. The primary outcome is event-free survival. Secondary outcomes include additional efficacy end points and safety. The target sample size is around 1000 participants.

Non-muscle-invasive bladder cancer (NMIBC) is the most common type of bladder cancer. Most people have surgery to remove the cancer cells while leaving the rest of the bladder intact. This is called transurethral resection of a bladder tumor (TURBT). For people with high-risk NMIBC, a medicine called Bacillus Calmette-Guérin (BCG) is placed directly inside the bladder after TURBT. A 'high risk' classification means that the cancer is more likely to spread or come back after treatment. Some people's cancer does not respond to BCG or returns after BCG treatment. Researchers are currently looking at whether BCG combined with other immunotherapies may prevent cancer growth more than BCG on its own. Immunotherapy helps the immune system recognize and kill cancer cells. Sasanlimab is an immunotherapy medicine that is not yet approved to treat people with NMIBC. It is given as an injection under the skin. In this CREST study, researchers are looking at how safe and effective sasanlimab plus BCG is for people with high-risk NMIBC. Around 1000 people are taking part in CREST. They must have had TURBT 12 weeks or less before joining the study. Researchers want to know how long people live without certain events occurring, such as bladder cancer cells returning. A plain language summary of this article can be found as Supplementary Material. Clinical Trial Registration: NCT04165317; 2019-003375-19 (EudraCT) (ClinicalTrials.gov).

Patient and Healthcare Professional Perspectives from ESMO 2021 on Bladder and Kidney Cancer: A Podcast.

In this plain language podcast, highlights from the European Society for Medical Oncology (ESMO) Congress 2021 are discussed from the perspective of both a patient and a healthcare professional. The patient advocacy track at the congress was co-developed with patients, and was integrated into the overall programme. It included four sessions on the financial impact of cancer, treatments that use the body's immune system to fight cancer, technology, and rare cancers. This comes at a time when there is an increasing focus on the value of real-world data (data from a real-life setting, rather than in a clinical trial) and a more active role for patients and patient organisations as partners in research. Challenges and opportunities arising during the COVID-19 pandemic were also discussed, including logistical complexities in healthcare and consequent uncertainty for patients in accessing care, and opportunities including increased use of telemedicine and broader participation offered by virtual/on-site hybrid congress formats, as used in ESMO 2021. Data discussed on combination treatments for patients with bladder cancer suggest an improved chance of remission for patients intolerant or resistant to existing treatment. Some of the data from studies in kidney cancer also suggest that treatment breaks or longer periods between treatment can improve quality of life and reduce treatment costs, without reducing treatment effectiveness. Although data on bladder and kidney cancer studies were seen to be promising, the authors recognise the time it takes for such findings to reach clinical practice, and the importance of managing expectations in the patient community. The authors conclude their discussion by reflecting on key challenges and opportunities moving forward, including restoring and improving care and efficiency of cancer services, and working together with patient advocates and advocacy organisations as essential partners in achieving this. ESMO Podcast video.

Learning from Crisis: a Multicentre Study of Oncology Telemedicine Clinics Introduced During COVID-19.

The COVID-19 pandemic has necessitated adaptation of cancer patient care. Oncology patients who contract COVID-19 have poor outcomes. Telemedicine clinics (teleclinics) have been introduced for cancer patients to reduce the risk of horizontal transmission at St. Bartholomew's Hospital and The Royal Free Hospital in London. Teleclinics have become routine in many specialities; however, inclusion in oncology care was not standard prior to the pandemic. A mixed-methods survey was designed and delivered to cancer patients (n = 106) at St. Bartholomew's Hospital and The Royal Free Hospital who had transitioned to teleclinics in March 2020. The survey explored patients' perceptions of this format. In total, 96 (90.5%) patients consented to take part, across a range of tumour types. Overall, respondents reacted favourably to the format of the teleclinics, with 90.6% of respondents (87/96) stating they would utilise teleclinics beyond the pandemic. Additionally, a survey was distributed to clinicians delivering these teleclinics (n = 16) to explore previous training in, perceptions of, and lessons learned from the introduction of telemedicine. Results suggest patients are accepting of teleclinic use for most clinical purposes. Teleclinic implementation affords benefits to cancer patient care both during and after COVID-19, but there is an urgent need for telemedicine education in oncology specialty training.

Enhancing the in vitro cytotoxic activity of Delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach.

Delta(9)-Tetrahydrocannabinol (THC) is the active metabolite of cannabis, which has demonstrable cytotoxic activity in vitro. In support of our previously published data, we have investigated the interactions between THC and anti-leukemia therapies and studied the role of the signalling pathways in mediating these effects. Results showed clear synergistic interactions between THC and the cytotoxic agents in leukemic cells. Additionally, exposure of cells to sub lethal levels of THC (1 microM) sensitised cells to these cytotoxic agents, by reducing IC(50) values by approximately 50%. Sensitisation appeared to be dependent upon the ability of THC to down regulate phosphorylated ERK, as cells dominantly expressive of MEK were not sensitised to the cytotoxic drugs by equi-molar amounts of THC. Overall, these results demonstrate for the first time that a combination approach with THC and established cytotoxic agents may enhance cell death in vitro. Additionally the MAPK/ERK pathway appears responsible in part for these effects.

The changing presentation of germ cell tumours of the testis between 1983 and 2002.

OBJECTIVE: To prospectively investigate the presentation of germ cell tumours (GCTs) of the testis in terms of stage or histology, as the incidence of this disease in increasing. PATIENTS AND METHODS: Patients diagnosed with GCT of the testis between 1983 and 2002 were categorised into three periods depending on the date of diagnosis of the GCT, and the presentational characteristics assessed. RESULTS There was a significant increase in the proportion of patients presenting with stage I disease (59% to 78%) and seminoma (43% to 58%) over this period. There was also a significant reduction in the size of the primary tumour (5 to 4 cm). CONCLUSION: A greater proportion of patients with GCT are presenting with stage I seminoma, the reasons for which are unclear, although earlier diagnosis through improved awareness of GCT may be important.