Introducing the JUPITER project A promising step towards evidence-based focal therapy for PCa
in patients with clinically localised PCa. Due to the lack of high-quality evidence, the JUPITER study has been developed. JUPITER is a new prospective multicentre (and not randomised) European registry for patients undergoing FT for localised prostate cancer. It has been developed under the umbrella of the EAU Research Foundation who will set up the database using the Castor study management system. The principal investigators and directors of the research are Dr. Eric Barret (FR) and Prof. Juan Martinez- Salamanca (ES). “JUPITER could become the means to obtain the evidence on focal therapy that many clinicians and surgeons involved in the care of prostate cancer are waiting for!” At least 1,000 patients will be recruited for 2 years in European centres already experienced in FT. Inclusion criteria are related to: patients characteristics (age ≥ 18 years, WHO performance status 0 or 1, no prior treatment for PCa and diagnosis of intermediate-risk PCa according to D’Amico’s 2003 risk group categories), mpMRI findings (detection of single lesion suspected PCa lesion on mpMRI < T3, with PI-RADS ≥ 3 and tumour localisation according to the segmentation model used in PI-RADS v2), biopsy modalities (with a systematic biopsy US-MRI fusion technique performed with a number of cores ≥ 3 per target), and pathological analysis (ISUP 2 or 3 within the target, with ISUP 1 outside the target acceptable if low volume).
Dr. Eric Barret Institut Mutualiste Montsouris Paris (FR)
eric.barret@imm.fr
Prof. Juan Martinez- Salamanca Hospital University Puerta de Hierro- Majadahonda and Lyx Institute of Urology Madrid (ES)
jims09@me.com
In recent years the earlier diagnosis of prostate cancer (PCa) and the increased detection of small and clinically insignificant PCa has highlighted the need to reduce possible overtreatment and preserve a patient’s quality of life (QoL). In this context, focal therapy (FT) represents an ideal therapeutic option to achieve these objectives in selected patients and is a hot research topic in this field. Already in 2018, FT was considered as a possible and significant option for PCa care [1]. The most recent systematic review concluded that “more high-quality evidence is required before FT can become a standard treatment” [2]. The current EAU guidelines [2] recommend that FT can be applied “within a clinical trial setting or well-designed prospective cohort study” and states that “sufficient data are available to form the basis of some initial judgements” for FT
Eric Barret and Juan Martinez-Salamanca (principal investigators of JUPITER)
up, using several energy sources currently available. The secondary end points include the outcomes by energy, based on MRI, PSA changes and control biopsy, up to 60 months following the treatment.
Reference 1. van der Poel HG, van den Bergh RCN, Briers E, et al. Focal therapy in primary localised prostate cancer: The European Association of Urology position in 2018. Eur Urol. 2018;74(1):84-91. doi:10.1016/j.eururo.2018.01.001 2. Hopstaken JS, Bomers JGR, Sedelaar MJP, Valerio M, Fütterer JJ, Rovers MM. An updated systematic review on focal therapy in localised prostate cancer: What has changed over the past 5 Years? Eur Urol. 2022;81(1):5- 33. doi:10.1016/j.eururo.2021.08.005 3. EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam 2022. ISBN 978-94-92671-16-5
Finally, in case of failure, the salvage treatments and their complications will be analysed.
If the study proves FT to be oncologically safe, and reduces the impact on patients’ urinary and sexual functions, it could become a valuable evidence-based therapeutic tool for both patients and urologists.
The primary endpoint of JUPITER is the oncological efficacy of FT for localised PCa at 12 months follow
EAU Research Foundation
ADVERTORIAL
Circulating tumour DNA-guided treatment for high-risk, post-cystectomy muscle-invasive bladder cancer Adjuvant atezolizumab for muscle-invasive bladder cancer using a minimally invasive biomarker approach
Prof. Thomas Powles Barts Cancer Institute Queen Mary University of London ECMC
an unselected label in the United States but requires tumour cell PD-L1 expression ≥1% in Europe.[2,3] The use of blood levels of circulating tumour DNA (ctDNA) as a biomarker for disease detection and recurrence has been demonstrated in multiple cancer types.[4] ctDNA is highly prognostic in MIBC[5] and may aid in risk stratification to inform post-surgical disease management, including determining which patients with ctDNA-negative status may be spared adjuvant therapy. It also represents a less invasive alternative to follow-up tissue biopsies, allowing for earlier detection of recurrence and potentially removing barriers to frequent testing of mutation status. An exploratory analysis from the phase III IMvigor010 study used ctDNA positivity as a surrogate for molecular residual disease to enrich for patients who may derive disease-free survival (DFS) or OS benefit with the checkpoint inhibitor atezolizumab compared with observation as well as to identify patients who could be spared adjuvant treatment [6,7]. These hypothesis-generating data provided rationale for further investigation of the role of ctDNA in MIBC management in the ongoing phase III IMvigor011 study. IMvigor011 (Figure 1) is enrolling patients with high-risk MIBC to undergo serial ctDNA surveillance after cystectomy; patients with ctDNA(+) status, as determined using a personalised panel (tumour-informed) assay (Natera Signatera) will be randomised to adjuvant atezolizumab vs placebo (2:1). Patients who are ctDNA(–) will undergo surveillance for ctDNA relapse. Serial ctDNA surveillance after
Barts Health London (GB)
While progress has been made against bladder cancer as a whole, there are still large subsets of patients with high unmet needs and a lack of clear guidance on how to treat them. For example, some patients with muscle-invasive bladder cancer (MIBC) who are at high risk for disease recurrence following cystectomy (pT3/T4 or N+), including those unable to receive neoadjuvant cisplatin-based chemotherapy, may benefit from adjuvant treatment. However, no data demonstrating overall survival (OS) benefit exist to guide patient selection and treatment. To address this ongoing dilemma, biomarker-based personalised approaches have been pursued in urothelial carcinoma since the adoption of immune checkpoint inhibitors and other targeted agents. PD-L1 is one consideration in selecting patients who may derive benefit from checkpoint inhibitors in some treatment settings; however, challenges exist in its applicability, including diagnostic assay
Fig. 1: The IMvigor011 study (principal investigator: Thomas Powles) is enrolling patients with MIBC at 194 sites internationally. NAC, neoadjuvant chemotherapy; SOC, standard of care; WES, whole-exome sequencing.
Reference 1. Powles T. Adjuvant immuno-oncological treatment (next steps in immunotherapy for GU malignancies session). EAU 2023. Milan, Italy. 12 March 2023. 2. Opdivo (nivolumab). Prescribing information. Bristol Myers Squibb; 2023. 3. Opdivo (nivolumab). Summary of product characteristics. Bristol Myers Squibb; 2023. 4. Stadler JC, et al. Cancer Res 2022;82:349-358. 5. Szabados B, et al. Eur Urol. 2022;82:212-222. 6. Gschwend JE, et al. Overall survival by circulating tumor DNA status in patients with post-operative muscle- invasive urothelial carcinoma treated with atezolizumab: update from IMvigor010 (session GS5). EAU 2022. Amsterdam, the Netherlands. 4 July 2022. 7. Powles T, et al. Nature . 2021;595:432-437. 8. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/ NCT04138628. Accessed 29 March 2023.
cystectomy allows an intervention window before radiographic recurrence occurs. The primary endpoint is investigator-assessed DFS in patients who are ctDNA(+) within 24 weeks of cystectomy. Key secondary endpoints include OS in this population, investigator-assessed DFS in all randomised patients, and centrally reviewed DFS. Notwithstanding the importance of selecting the appropriate patient subset for adjuvant therapy, preventing overtreatment of patients who may not relapse is another key piece. Given the promise of ctDNA, we are excited to enrol patients in the IMvigor011 study evaluating adjuvant immuno- therapy in patients with MIBC to prospectively test ctDNA as a biomarker, while we await results from other ongoing studies evaluating serial ctDNA testing for relapse detection (e.g., TOMBOLA, a phase II adjuvant atezolizumab study).[8]
choice, and are reflected by differences in recommendations between global health
authorities.[1] For example, in the adjuvant setting, the checkpoint inhibitor nivolumab is approved with
European Urology Today
28
April/May 2023
Powered by FlippingBook