Tag Archive for: Tumour

Posts

TRoMbone is launched!

TRoMbone is launched! The UK feasibility randomised trial Testing radical prostatectomy in men with prostate cancer and oligoMetastases to the bone has opened at Oxford University Hospitals (PI Freddie Hamdy), University College London Hospitals (PI John Kelly) and Royal Surrey County Hospital (PI Chris Eden). Men <75 with newly-diagnosed prostate cancer and 1-3 skeletal lesions on any standard-of-care imaging (CT, bone scan, MRI, or PET) who are fit for surgery and deemed to be technically operable are eligible. Emerging but lower-quality data suggests a role for treatment of the primary tumour in men with oligo-metastatic prostate cancer and this UK study will investigate this question with level 1 evidence.

Participants will be randomly allocated to standard-of-care treatment (hormones +/- chemotherapy) versus standard-of-care treatment plus surgery to remove the prostate and draining lymph nodes (radical prostatectomy plus extended pelvic lymphadenectomy). A qualitative recruitment investigation to optimise accrual will be conducted by the University of Bristol (Caroline Wilson) and biologic samples will be collected, processed and stored in a repository at the Institute of Cancer Research (Gerhardt Attard).

We will assess technical feasibility, safety and complications of surgery in oligo-metastatic prostate cancer, and examine ways to improve recruitment in this pilot study. TRoMbone is managed by the Surgical Intervention Trials Unit at the University of Oxford and funded by the Prostate Cancer Foundation and The Urology Foundation.

We need to recruit 50 men over a 12-month period, and are seeking referrals from other centres to increase accrual. Centres that demonstrate ability to refer eligible patients will be able to take part in the main trial if we can demonstrate feasibility in this phase and get funding for the larger study.

So please look out for these patients and send them to me at UCLH, Freddie in Oxford, or Chris in Guildford. One of the three of us will do the surgery if they get randomised to it, but of course you’re welcome to come with the patients. If you have any queries please contact me, the study CI (P. Sooriakumaran (PS); [email protected]) or the study co-ordinator (Neelam Hassanali; [email protected]). You can start them on androgen deprivation and ‘stop the clock’ before you refer them to us. The extra burden of participating in this study is minimal. They will require one visit for consent, and one follow-up visit at 3 months after randomisation. The surgical group will also have two other visits for their surgery and catheter removal. The rest of the follow-up can be done back at your referring centre or with us, whatever you and the patient prefer. If it’s your standard policy to give them chemotherapy or metastasis-directed therapy with SBRT then you can still do that as part of the study.

 

With your help we can demonstrate that this study is feasible in the UK and we can lead the way in the surgical management of oligo-metastatic prostate cancer.

 

P. Sooriakumaran [social type=”facebook” opacity=”dark’ label=’PLACE_LINK_HERE[/social]

BMedSci(Hons) BMBS(Hons) PhD PGCMedLaw ADCClinInv FRCS(Urol) FEBU USLME

Consultant Urological Surgeon, UCL Hospitals NHS Foundation Trust & Honorary Clinical Senior Researcher, University of Oxford

 

Immunotherapy in urological malignancies: can you take your knowledge to the next level?

bju13648-fig-0001In this month’s issue of the BJUI, we highlight the evolving era of immunotherapy in solid tumour therapy. As urological surgeons, we spend a large portion of our time working with anatomy, instruments, and robots – things we can see, touch, and control. Immunotherapy is a different conversation – cartoon pathways, process blockades, molecular expression levels, combination therapies, and treatment resistance. Curing a patient with a successful operation is a major draw to our field, but we know our limitations when faced with lethal variant prostate cancer, and high-grade/high-stage bladder and kidney cancers in particular. Systemic therapies have been around for decades and are part of our guidelines – so why all the excitement over immunotherapy?

Our highlighted articles are a review from Mataraza and Gotwals [1] and a comment from Elhage et al. [2]. I urge you to start with the review article [1] and give it a full line-by-line read. You may need to pull out pen and paper, and practice spelling and pronouncing a number of new compounds. They may sound as awkward as abiraterone did the first time you heard of it years ago but will eventually become familiar and attached to yet another catchy trade name from pharma. Here is a quick list/homework assignment: ipilimumab, nivolumab, pembrolizumab, pidilizumab, atezolizumab. Another 20 or more are in development. Challenge yourself to write out their pathways, and you may re-learn a thing or two about familiar agents like sipuleucel-T, interferon α, and interleukin 2.

A major theme in both articles is the experience with immunotherapy in advanced melanoma. The enticing message is that a cohort of patients with metastatic melanoma treated with ipilimumab survived 3 years and the Kaplan–Meier curves plateau out to 10 years. This observation sparks different possible futures such as immune ‘memory’, durable response, and ultimately the word we like to use in surgery – cure.

The picture in urological cancers is not entirely as rosy as the melanoma Kaplan–Meier curve. Multiple trials are highlighted by our review with familiar themes of single agent trials, combination immunotherapies, and combined immunotherapy plus anti-angiogenesis agents. Many trials enrol heavily pre-treated populations with limited remaining options. Many endpoints still observe responses followed by resistance patterns. An important theme to follow is the coupling of biomarkers that link expression to treatment response (i.e. predictive vs prognostic), and the USA Food and Drug Administration (FDA) has approved such a biomarker for nivolumab response. However, even this story line is perplexing, as drug response is not always linked to the marker, and immune cell expression may be ‘inducible and dynamic’ [1].

Last step – re-read the review and comment articles and see if you can write down some key agenda items for future immunotherapy. How are checkpoint inhibitors different from vaccines? How do we generate a durable immune response? What is the ‘abscopal effect’? What are three major areas of research and development in immunotherapy?

If you can spend the time on these articles and ponder these challenging questions, you will move up to the next level of understanding and enjoy a greater appreciation of the next abstract you hear at a major meeting. In closing, I am reminded of the oft-repeated words from the hit television show Game of Thrones (based on the novels of George R.R. Martin) from the House Stark: ‘Winter is Coming’. In urological oncology, ‘Immunotherapy is Coming’, so be prepared!

 

John W. Davis

BJUI Associate Editor Urological Oncology

 

References

1 Mataraza JM, Gotwals P. Recent advances in immuno-oncology and its application to urological cancers. BJU Int 2016; 118: 50614

 

2 Elhage O, Galustian C , Dasgupta P. Immune checkpoint blockade treatment for urological cancers? BJU Int 2016; 118: 498505

 

© 2021 BJU International. All Rights Reserved.