The audience was presented with the most up-to-date statistics and preliminary conclusions from the SPCG4 study, the ARAMIS trial, KEYNOTE 057, with further lectures concerning first-line treatment options for metastatic RCC and the duration of ADT in high-risk PCa. Each presenter was followed by a discussant from a complementary specialty and many further talking points coming from the audience.

ARAMIS

It was Prof. Karim Fizazi’s talk on the ARAMIS trial and the potential for the use of darolutamide for non-metastatic, castration-resistant prostate cancer (m0 CRPC) that led to a lot of discussion. M0 CRPC is considered to be a quite rare situation, so treatment has so far been an unmet need. Primary endpoints were improved overall survival and time to pain progression.

Darolutamide’s structure might be the explanation for its low blood-brain barrier penetration, leading to fewer side effects and better tolerability when compared to enzalutamide and apalutamide (PROSPER and SPARTAN trials respectively).

Fizazi concluded based on the latest results that all three agents showed clear and meaningful improvement of metastasis-free survival, with Darolutamide, in particular, showing a remarkable safety profile. The preliminary results clearly suggested improvement in pain progression and overall survival.

Not only his ‘discussant’ Prof. Maria De Santis added new insights, but the audience too had questions about the potential of darolutamide vs. enzalutamide and apalutamide.  While the results of darolutamide and the ARAMIS trial are very good, particulary, the tolerability, the price point may yet be an important factor when choosing between the drugs, Fizazi pointed out.

De Santis pointed out changes in the 2019 EAU Guidelines that gave a strong recommendation for APA or ENZA for patients with m0 CRPC, and expected the 2020 Guidelines to do the same for Darolutamide, based on these new results. This was clearly the “Guideline-changing potential” that Dr. Maurer expected from the session beforehand.

Challenges when comparing trials

Prof. Pär Stattin on the SPCG4 Trial. The trials compared radical prostatectomy vs watchful waiting in early prostate cancer and recruited 695 men between 1989-1999. It spawned five major publications in the New England Journal of Medicine in 2002, 2005, 2011, 2014 and 2018.

At EMUC19, Stattin explored whether the absolute risks of death from the trial were applicable to current patients undergoing radical prostatectomy. Unfortunately, the trial did not collect data on prostate volume (and therefore density), the extent of cancer on biopsy or the comorbidities, making this a challenge.

Further challenges for those wishing to draw lessons out of a twenty-year-old trial are what Stattin referred to as “Gleason grade inflation” that required compensation. Broadly concluded, the absolute risk of PCa death in SPCG-4 is not applicable to men undergoing radical prostatectomy in 2019. Furthermore, comprehensive data on changes in detection, cancer characteristics and work-up have to be considered in order to interpret data in old trials.

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“It is up to well-designed prospective studies to determine their exact indication and place in the landscape in the treatment of metastatic uro-oncology patients. But established therapies and treatment regimens also need to be re-evaluated, for instance the duration of androgen deprivation in primary radiotherapy for localised high-risk prostate cancer.”

Dr. Maurer is co-chairing the ‘New Trials Update’ session at EMUC19, the 11^th European Multidisciplinary Congress on Urological Cancers. This session will give participants an update on upcoming and currently running trials in onco-urology. Maurer: “The presented studies and data all serve to guide the practising urooncologist in their treatment decisions.”

EMUC19 is a collaboration between the European Society for Medical Oncology (ESMO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Association of Urology (EAU). Other chairs of the session are radiation oncologist Dr. Carl Salembier (Brussels, BE) and medical oncologist Prof. Aristotelis Bamias (Athens, GR).

Dr. Maurer currently serves on the Faculty of the Martini-Klinik Prostate Cancer Center at the University of Hamburg-Eppendorf, having joined in July 2018. Previously he was the Senior Attending Physician and Vice Chair at the Department of Urology of the Technical University of Munich. His current main focus is staging, surgical and medical treatment of prostate cancer.

EMUC19 will take place in Vienna (AT) on 14-17 November, also featuring the 8^th Section Meeting of the EAU Section of Urological Imaging, courses by the European School of Urology and many more optional sessions and meetings. The annual EMUC congress is unique in its multidisciplinary approach to urological cancers, featuring speakers from a huge variety of oncology-related disciplines in an attractive and focused scientific programme.

Anticipating results

The New Trials session on Saturday morning (Plenary Session 7) will cover new and ongoing trials like SPCG4, ARAMIS and KEYNOTE 057. Each trial will be presented by a specialist from one discipline and then discussed with another specialist, highlighting the multidisciplinary approach that is favoured for onco-urological conditions.

Results of these trials are hotly anticipated by oncologists and urologists alike, according to Dr. Maurer:

“Although some of the presented studies have recently been presented at other meetings or published in full, updated data will be presented at EMUC19. In this respect, medical oncologists, but also radiation oncologists and urologists who treat onco-urology patients should clearly take the chance to attend this careful selected session to confirm and update their knowledge.”

“For example, in mRCC patients, the longer life expectancy makes sequential therapy likely. In this case the first-line treatment already strongly influences and guides sequential therapy, due to several approved classes of agents in metastatic renal cell cancer. Thus, several considerations have to be taken into account when choosing the initial therapy regime. The introduction of immunotherapy opened a whole new field of therapeutics especially in bladder cancer. For instance, Pembrolizumab could add a new potent option in BCG-refractory non-muscle-invasive bladder cancer.”

One example of a trial that will have an impact on daily treatment is the ARAMIS trial. Maurer: “It not only showed significantly increased metastasis-free survival with darolutamide compared to placebo in non-metastatic CRPC patients, but also significant advantages for overall survival, time to pain progression and time to symptomatic skeletal events. These are all relevant endpoints for men suffering from nmCPRC. At the same time an increase in incidence for adverse events was not observed.”

“These findings will likely soon impact daily treatment in this specific patient cohort. But, as mentioned above, the other presented studies also have guideline-changing potential.”

Emerging treatment options

Trials have a huge potential for changing guidelines and treatment options, according to Dr. Maurer: “These days medical oncologists, urologists and radiation oncologists face an increasing number of therapeutic possibilities for systemic treatment of prostate, bladder and renal cell cancer.”

“The trials presented at EMUC19 add significantly to our knowledge and will influence our insights on these diseases – which treatment sequence should be chosen in each individual patient or even if treatment is necessary at all and watchful waiting might be the best option. However, surely we can expect further advancements on our way to personalised and individualised cancer treatment in the future.”

As the EMUC congress represents the medical world’s commitment to multidisciplinary approach, onco-urological trials also reflect the cooperation of the involved disciplines.

“Within the last years we can observe an ever-increasing cooperation between the different medical disciplines in daily practice within interdisciplinary and even molecular tumour boards. Due to the increasing complexity of multimodal treatment regimens this is on the other hand a prerequisite for successful modern onco-urology.”

Dr. Maurer feels that the EMUC congress sets a great example: “It has been a great success since its introduction as a platform for mutual exchange between medical oncologists, urologists, radiation experts as well as (not to forget!) imaging specialists. The ESUI’s annual meeting has recently become a valuable ‘pre-congress’ to EMUC. As specialists, I think that we can all agree that multidisciplinary management of onco-urological patients is integral to our success!

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Dr. Collette spoke as part of the Friday morning session on prostate cancer at the 10th European Multidisciplinary Congress on Urological Cancers (EMUC18) in Amsterdam. She offered a biostatistician’s perspective in the two-hour session that also included pathologists, urologists, radiation and medical oncologists and research scientists. Dr. Collette is the senior manager in charge of statistics and independent data monitoring at the European Organisation for Research and Treatment of Cancer (EORTC).

Good evidence in challenging times

Tasked with offering a view on evidence gathering in 2025, Dr. Collette spoke of trials taking place in a “fast-changing, high-tech and economically challenging environment.” She pointed out five major themes: which drugs work (best), which sequence, the impact of modern imaging, new technologies and the emergence of big data.

On drug trials: “Typically, trials end up adding to existing treatments. Their controlling arm is usually placebo, and the trial is focused on rapid authorization before the long-term information is available.” Collette cited the PROSPER trial, praising its results. Nevertheless, she considers it striking that information about the patient’s quality of life is only collected until the time of progression, without any information available for a complete assessment of the treatment.

“Trials should be designed not just to achieve clearance for the drug or treatment in question, but ultimately to inform healthcare systems on which treatment is effective for the patient and worth the investment. We need to move on from drug-centered to patient-centered trials.”

In order to determine which drugs work best, parallel and comparative studies are needed. Collette quoted the STAMPEDE trial as a good example of a flexible, adaptive trial that compares different treatment options in different arms that could be added or stopped early. “This leads to practice-changing results in a much shorter time than sequential trials. This requires pharmaceutical companies to work together, and here academia can play a role.”

With regards to new technologies: “There is a danger of a catch-22 situation: people need to buy the technology to test it, but are compelled to use it once the investment has been made.”

The application of big data in cancer research has its potential in the near future, as well as some challenges, according to Prof. Collette: “Big data in oncology is obviously not on the scale of Google’s use of data, or social media. It can also not be monitored on a day-by-day basis, unlike conditions that can be monitored through wearable devices like blood pressure or heart rate.”

“Furthermore, there is the challenge of new laws. We are currently trying to negotiate an exception to the GDPR rules that impact our trials by preventing us from sharing data or in some cases even invalidating existing data.”

In summary, for generating good evidence in the coming decade: “Patient-centric trials are the future, as are multi-stakeholder collaborations with more than one company. Effective digitalization of our results will lead to bigger data for researchers.”

Predictive statistics

The morning continued with a session on controversies and contradictions in the staging of prostate cancer. This mainly took the form of an hour-long multidisciplinary case discussion concerning a 69 year-old man with hypertension and a PSA of 14.7, a family history of PCa but no suspicious lesions after a DRE was performed. Sixteen cores were taken in a random TRUS biopsy. A panel of six experts debated the course of action.

Preceding the case discussion was a presentation by Dr. Daniel Sjoberg (New York City, USA), biostatistician of Memorial Sloan Kettering Cancer Center who in the past also worked to develop the 4Kscore.

“Recently, there has been a huge increase in modern markers for prostate cancer,” Dr. Sjoberg began. “We are starting to move beyond the ROC curve, which is insufficient for making a useful clinical prediction. We need make a more pragmatic assessment of these markers.”

Dr. Sjoberg lined out three qualities that make a good biomarker: discrimination, calibration and ultimately clinical utility.

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