The Bench-to-Bedside GU Cancer Triad Meeting was organized by the Société Internationale d’Urologie and was held in Berlin, Germany on December 13th and 14th. This one-and-a half-day meeting brought together an impressive faculty led by the Scientific Programme Chairs, Drs. Peter Black (Canada), Pilar Laguna (Turkey and The Netherlands), Rafael Sanchez-Salas (France) and Peter Hammerer (Germany). The meeting also offered an opportunity for the participants to obtain CME credits as the event was accredited by the Ärztekammer Niedersachsen and the Ärztekammer Berlin for 12 training points, and by the European Accreditation Council for Continuing Medical Education (EACCME®) with 11 European CME credits (ECMEC®s).
The meeting focused on three major uro-oncological cancers that are undergoing a rapid evolution in treatment: bladder and kidney cancers, which was tackled on Day 1, and prostate cancer, which was the focus on Day 2. The meeting comprised of important knowledge gained from research, as well as practical tips for the clinic. Between the lectures, several educational opportunities in the form of expert panel case discussions as well as speaker’s corner were offered. There were more than 100 registrants onsite and the meeting, which was broadcasted live from Berlin via SIU Academy, garnered over 3,000 online participants from around the globe!
Day 1: Drs. Peter Black and Pilar Laguna welcomed everyone to the Bladder and Kidney cancer session. The bladder cancer session covered immunotherapy (IO) in metastatic urothelial carcinoma and localized muscle-invasive disease, as well as novel therapies in non-muscle invasive disease. Dr. Petros Grivas (United States) opened the meeting with a presentation on immunotherapy in metastatic urothelial carcinoma. He highlighted important emerging research on first-line IO in cisplatin-ineligible and cisplatin-eligible patients and in the post-platinum setting. He reviewed the indications of PD-1/PD-L1 inhibitors in the second-line setting and discussed the impact of ongoing trials in first line. There continues to be a need for prospective biomarker validation to select the appropriate treatment regimen at the right time for the right patient.
Dr. Grivas moved on to discuss the role of perioperative immunotherapy in addressing current unmet medical needs in muscle-invasive bladder cancer (MIBC). He presented summaries of several investigator-initiated neoadjuvant trials of immune-checkpoint blockade before radical cystectomy (e.g., PURE-01, ABACUS, NABUCCO, BLASST-1 etc.). He indicated that neoadjuvant chemotherapy is still the standard of care in the neoadjuvant setting, and neoadjuvant immunotherapy is still considered experimental, but ongoing trials will soon tell us if there is potentially a role for both, either alone or in combination. Dr. Wassim Kassouf (Canada) followed with a forward-looking presentation on combining trimodal therapy with checkpoint blockade for patients with MIBC. Ongoing trials will determine if this is efficacious, and will define the optimal sequence of treatment delivery.
Dr. Peter Black covered immunotherapy and other evolving therapies in non-muscle invasive bladder cancer (NMIBC)). He opened his presentation with the key definitions of BCG-unresponsive NMIBC and outlined the current limitations in intravesical salvage therapy in this setting. He provided an overview of the emerging novel intravesical therapies that are being tested in clinical trials, some of which are under review for FDA approval. He also highlighted early trial results of systemic IO for patients with BCG unresponsive NMIBC. The next steps include moving to earlier disease states as well as ongoing testing for optimal sequencing and combination therapy. It is also important to identify the factors that will determine appropriate treatment selection, e.g., whether it is intravesical or systemic therapy.
During the discussion session, questions were raised about the DANUBE trial (including combination of tremelimumab (anti-CTLA4) and durvalumab (anti-PDL1) in the first-line metastatic setting), the benefit of the combination of IO and platinum chemotherapy (IMvigor 130), especially in comparison to the efficacy of sequential therapy, and the effect of combining treatment modalities on bladder preservation. Discussions also included the role of neoadjuvant immunotherapy followed by cystectomy and how we are waiting on more data to guide possible paradigm changes.
Dr. Christian Kollmannsberger (Canada) provided an overview of the current landscape of immunotherapy (IO) in metastatic renal cell carcinoma (RCC). In the “new” immunotherapy era, immunotherapy combinations (e.g., nivolumab/ipilimumab) and immunotherapy/tyrosine kinase inhibitors (TKI) combinations (e.g., avelumab/axitinib and pembrolizumab/axitinib) are at the forefront of therapeutic advances in metastatic RCC. Notable clinical trials include Checkmate-214, JAVELIN Renal 101, and KEYNOTE 426.
Dr. Michael Staehler (Germany) led an interactive case-based panel discussion with Dr. Axel Bex (The Netherlands), Dr. Dirk Böhmer (Germany), and Dr. Christian Kollmannsberger. The cases highlighted especially the concept of multimodal therapy and how surgery fits into the treatment pathway since reporting of the CARMENA trial, as well as the importance of patient preference during the treatment decision-making process. The increasing role of stereotactic radiation for metastatic disease was also discussed.
Dr. Viktor Grünwald (Germany) presented on the role of perioperative IO and targeted therapy in high-risk RCC. He described the negative results from trial investigating adjuvant TKIs, but also discussed emerging evidence suggesting the role for adjuvant treatment with the TKI plus checkpoint inhibitors in the adjuvant therapy setting.
Dr. Kilian Gust led a case-based discussion on adverse events and toxicities associated with immunotherapy. The panel of experts included Dr. Christian Kollmannsberger, Dr. Pablo Maroto Rey (Spain), and Dr. Srikala Sridhar (Canada). Before discussing the cases, some general side effects/adverse events (AEs) were presented, including fatigue, infusion-related AEs and organ-specific immune-related adverse events (irAEs). Dr. Gust outlined the important steps to follow before starting treatment with immunotherapy, in order to prepare for and manage treatment-related toxicities and adverse events.
A subsequent panel discussion led by Petros Grivas (US) with Drs. Peter Black, Gopa Iyer, and Tilman Todenhöfer covered several important concepts regarding the clinical utilization of biomarkers in advanced bladder cancer, such as the use of comprehensive genomic profiling to identify the optimal candidates for neoadjuvant therapy. The patient case scenarios discussed were based primarily on metastatic disease. The key question is: how can we improve the biomarker-based patient selection within the next-generation of trials?
Dr. Lisa Derosa’s (France) presentation focused on the fundamentals of microbes and their role in the human body, particularly regarding the link between microbiota and cancer. Her lecture aimed to define the clinical relevance of the composition of the gut microbiome in tumor immunology by addressing questions about the impact of gut microbiota on cancer immunotherapy, the composition as it relates to impact on tumor response to treatment, as well as development of resistance to treatment. Novel approaches to treat cancer patients based on understanding microbiota composition and methods to modulate the microbiota to boost immune checkpoint blockade activity are needed.
In a session on emerging systemic therapies, Dr. Gopa Iyer (United States) presented on some of the tremendous advancements being made in targeted therapy approaches to urothelial cancer (UC) treatment. The mechanisms of FGFR3 activation and overexpression were also explained, as well as an outline of the other combinations and novel targeted therapies that are currently under investigation. Dr. Iyer emphasized that FGFR3 mutations should not preclude treatment with immunotherapy. The optimal screening methodology to select patients for FGFR inhibitor therapy is not yet defined.
Dr. Srikala Sridhar delivered an insightful presentation on the role of antibody drug conjugates (ADCs) in urothelial carcinoma. She outlined the key elements of ADCs. These basic components along with a clear portrait of the current UC treatment landscape are important for understanding how and where ADCs come into play. Dr. Sridhar highlighted trial results for enfortumab vedotin (EV) in third line treatment of patients with metastatic UC, after platinum chemotherapy and after IO. EV targets Nectin -4, which is expressed on the cell surface of almost all urothelial carcinoma. Early results suggest that this may also be highly effective in combination with immunotherapy.
Many unanswered questions remain with respect to optimal sequencing/combinations and continuing or switching PD-1/PD-L1 inhibitors in combinations. Moving forward, clinical trials with novel designs as well as multisite registries, databases, and biorepositories will be essential.
Day 2: Drs. Peter Hammerer (Germany) and Rafael Sanchez-Salas (France) welcomed attendees and online participants to the prostate cancer session. Dr. Derya Tilki (Germany) started the day with an excellent overview of the diagnostic and prognostic biomarkers in PCa, and explained their clinical utility using different case scenarios, as well as current needs in this area. This was followed by a session on the surgical (Dr. Sanchez-Salas) and radiotherapy (Dr. Alberto Bossi (France)) management of high-risk non-metastatic PCa, emphasizing the importance of a multimodal approach. A similar message prevailed in the session on management of oligometastatic PCa. Here, Dr. Sooriakumaran (United Kingdom) presented the data from the STAMPEDE study, focusing on treatment of the primary with either radiation and surgery. He discussed the exciting news that surgery may be included as another treatment arm in the STAMPEDE trial. Dr. Dirk Böhmer (Germany) presented on the evolution of metastasis and their complexities and the utility of RT to the metastatic sites, while Dr. Srikala Sridhar(Canada) described the state-of-the-art in 2019 for integration of systemic therapy in the treatment of de novo oligometastatic PCa. She suggested that novel imaging will change how we define the oligometastatic disease in the near future, and we will have to understand how this impacts how we treat patients. She also talked about the future of trials to address the benefit, as well as evaluate at the adverse effects of local therapy vs. metastasis-directed therapy and consider clinically relevant research endpoints and harmonizing patient populations in trials.
Several prominent speakers further explored challenging patient scenarios in an exciting and engaging case-based panel discussion about oligometastatic PCa. The panel included Drs. Dirk Böhmer, Karim Fizazi (France) Peter Hammerer, Srikala Sridhar, and Prassana Sooriakumaran. The discussion was moderated by Dr. Sanchez-Salas. Topics discussed included the importance of local therapy of metastatic disease, the use of conventional imaging versus next-generation imaging, the accessibility and cost of PSMA-PET in different countries and its incorporation in clinical trials, the discussion of the cases in multidisciplinary rounds, and follow-up of patients.
The second part of the session before the lunch break opened with a case-based panel discussion on managing biochemical recurrence after definitive local therapy. This session was moderated by Dr. Peter Hammerer and the expert panel included Drs. Alberto Bossi, Srikala Sridhar, Pablo Maroto Rey, Derya Tilki, and Rafael Sanchez-Salas.
Dr. Karim Fizazi, lead investigator of the well-known LATITUDE and ARAMIS trials, provided a state-of-the-art talk on systemic therapy for metastatic castration-sensitive and castration-resistant prostate cancer. Dr. Fizazi presented on how to best treat advanced PCa. He talked about the key messages from the recent trial results from the CHAARTED, STAMPEDE and LATITUDE trials. In his presentation, he indicated that early treatment clearly seems to be better in the setting of M1 CSPC, and M0 CRPC. He emphasized that the issue is not only on overall survival, but it’s also about the patient’s symptoms. The big question is should we use docetaxel or AR-targeted or both upfront in men with very aggressive disease? Sequential treatment is still routinely used in 2019 for CRPC while combination treatment is still experimental. There is cross-resistance between abiraterone and enzalutamide. His message was to stop the old-generation AR-targeting therapy approach and start using the next-generation drugs. The good news is that the taxanes remain active even after abiraterone and enzalutamide treatment. In mCRPC, we should use bone-protecting agents when we are using a combination of RT and AR-targeting agent. The best way to treat mCRPC is to personalize treatment. The future of PCa is now leading to biomarker-driven medicine.
Dr. Klaus Pantel followed with a talk on the clinical utility of liquid biopsy to support clinical decision-
The afternoon session focused on emerging research on systemic treatment for metastatic castration-resistant prostate cancer. Dr. Pablo Maroto Rey presented on the immunotherapy pipeline in PCa (vaccines, checkpoint inhibitors, and combination therapies, Dr. Peter Hammerer on PARP inhibitors, and Dr. Frederik Giesel (Germany) on PSMA-theranostics.
Dr. Maroto Rey indicated the challenges for vaccine therapy. Immunotherapy shows some efficacy in metastatic PCa, however, the percentage of patients who respond to these agents is low. He emphasized the importance of patient selection for identifying who will best benefit from immunotherapy. Immunotherapy may benefit those patients with low tumour burden and are affected by tumours with high mutational burden. Dr. Maroto Rey concluded that although the current landscape in immunotherapy for PCa is still not the best therapy at the moment, he believes that there will be more to come in this area in the future.
Dr. Peter Hammerer presented on Poly (ADP-ribose) Polymerase Inhibitors inhibitors (PARPis). He opened with the NCCN Guidelines and when genetic counseling and germline testing should be considered. The mutation load of PCa compared to other cancers is not that great. However, there is a certain percentage of men who show mutations and we may direct our treatment towards those men who are carriers of these mutations. Dr. Hammerer presented the current trials evaluating several PARPis in PCa patients with gene mutations. He provided an overview of the trials evaluating the clinical activity of olaparib in patients with alterations other than BRCA1 or BRCA2, as well as niraparib in patients with mCRPC and biallelic DNA-repair gene defects, rucaparib in patients with mutations to BRCA1/2 and other genes associated with DNA repair, as well as TRK inhibitors in patients with NTRK gene fusions. He concluded that relevant genetic mutations in PCa are rare, however targeting certain pathways show promising results, and personalized medicine for PCa is coming.
Dr. Giesel presented on a new era of imaging and therapy management: PSMA-theranostics. He provided an introduction on what PSMA is, as well as the current research and potential benefit with this approach. He presented a preview of the advances predicted in the future of the PSMA-theranostics approach.
Dr. Hammerer closed the meeting and thanked the SIU and everyone for attending the meeting onsite and online. Overall, this meeting succeeded in providing attendees a means to update their knowledge on the latest research and changing treatment paradigms in these uro-oncological cancers in one-and-a-half days. We were grateful for the positive feedback provided by the onsite attendees regarding the quality of the presentation topics and speakers of the meeting. This meeting not only offered an opportunity to obtain CME credits for participating, but also a way to network with colleagues, and acquire insights from the experts during the Q&A and panel discussions, as well as during the speaker’s corner session.