Last weekend, the Kidney Cancer Association (KCA) held its 10th European International Kidney Cancer Symposium in Lyon. The meeting brought together kidney cancer specialists and researchers from around the world to discuss current and future treatments for Renal Cell Carcinoma (RCC), and other considerations relevant to treatment. Videos of the presentations are available here.
Professor Hein Van Poppel opened the conference with the de Mulder memorial lecture discussing total and partial nephrectomies. Partial nephrectomies are associated with increased kidney function (Scosyrev et al., 2014) but not increased survival (Van Poppel et al., 2011). Although partial nephrectomies require more surgical skill it is possible to remove tumours <7cm, with minimal additional healthy tissue removed, with a low local recurrence risk.
Dr James Brugarolas spoke about the relevance of cancer genes in developing and selecting targeted therapies. A new HIF2α targeting drug is on the horizon and could be useful in targeting multiple tumourigenic pathways. Dr Brugarolas also discussed the subclassification of RCC patients based on mutations in the VHL, BAP1, and PBRM1 genes to screen for therapies effective in specific cohorts.
Dr Nizar Tannir discussed the development of new the immunotherapies – cancer vaccines that aim to stimulate the innate cancer immune response, and checkpoint inhibitors that blockade the immunosuppressant nature of tumours enabling an effective immune response. Further optimisation is required, including patient selection techniques, but immunotherapy could offer long term survival to suitable patients.
In the interdisciplinary discussions Dr Alessandro Volpe and Professor Bernard Escudier commented on how biopsies can be useful in diagnosis and play a role in selecting targeted treatments, but are invasive and unnecessary if irrelevant to proposed treatment. Professor Antoni Alcaraz and Professor Manuela Schmidinger discussed the increased use of minimalistic approaches to kidney cancer following advances in technology but warned against using potentially less effective techniques based on socio-economic pressure or trends. Dr Axel Bex and Dr Viktor Grünwald agreed that the choice to do a cytoreductive nephrectomy was patient dependent based on potential impact on tumour burden and quality of life. Dr Julien Garnon and Professor Jean-Jacques Patard commented on the high success rate of cryoablation as an alternative to surgery for tumours under 4cm.
There are several challenges presented to clinicians as a result of RCC treatments. Dr Christiane Thallinger discussed the high incidence of dermatological adverse effects in patients and the potential effects on dose reduction or treatment withdrawal. Dr Stephane Ederhy stated that hypertension was a common adverse effect with Tyrosine Kinases Inhibitor (TKI) treatments and that patients should be assessed and treated in advance, and be monitored carefully throughout. Professor Romano Danesi warned of the effects of variable TKI blood concentration in patients and the effect of other drug interactions that can impact on toxicity and efficacy. Dr James Larkin discussed the toxicity risks of checkpoint inhibitors and the need to educate patients and carers to these adverse events to enable early diagnosis and treatment.
The first day ended with a session concerning novel treatment targets. Dr Laurence Albiges discussed treatments that target FGFR signalling and MET signalling in clear cell (cc) RCC and non-ccRCC. Dr Primo Lara further discussed T-cell checkpoints with a focus on the PD-1/PD-L1 pathway and commented on the unanswered immunotherapy questions in RCC. Dr Eric Raymond discussed a regain of aberrant mTOR/AKT activity in tumours that evade sunitinib supporting the use of everolimus as a second line treatment. Dr Hans Hammers commented on the development and ongoing trials for cancer vaccines noting that it may necessary to use such treatments in combination with checkpoint inhibitors.
The second day of the conference began with a look back on recent trials and their impact on treatment plans. Professor Martin Gore commented that first line treatments have not changed and that the “smarter” drugs in development have not been as effective as hoped. Dr Cora Sternburg discussed optimal sequential treatment with a TKI being more efficacious as a first line treatment than a mTOR inhibitor, but both TKIs and mTOR inhibitors are recommended as a second line treatment. Professor Bernard Escudier spoke about the use mTOR inhibitors as a first line treatment in poor risk and non-ccRCC patients and the need for further trials to assess mTOR inhibitors in the less common papillary and chromophobe RCC cases. Dr Camillo Porta discussed the need for more third line treatment guidance and the need for more treatments in the future as patient survival increases.
This year’s Schonfeld Lecture was given by Professor Sylvie Négrier and was focused on the role of immunotherapy in metastatic RCC. Although immunotherapies have a relatively low response rate they are more likely to be durable. Future treatments might be made more effective by using knowledge of tumour specific antigens or neo-antigens. Immunotherapy treatments require optimisation especially with regards to combination therapies and adverse events.
The final session of the conference covered open questions in RCC treatment. Professor Alain Ravaud discussed the use of surgery to treat lung and liver metastases and ablation techniques when surgery was not an option. Dr Ronan Tanguy then discussed the use of radiotherapy alongside standard to treatments for liver, lung, brain and spinal metastases that are not suitable for surgery. Professor Tim Eisen gave his predictions for immunotherapy treatments by 2020 based on current trials, and discussed the need to consider patient fitness and symptoms in deciding on treatments with higher risk factors. Professor Tom Powles ended the conference by discussing the use of different imaging techniques to detect early metastases and monitor treatment responses.
The conference was a wonderful opportunity to hear from world leaders in kidney cancer treatment and hear about on ongoing trials and upcoming therapies. The treatment of hereditary renal cancers such as BHD can vary from sporadic renal cancer as the risk of further tumour development makes it more important to retain optimum kidney function through partial nephrectomies. Further biomarker classification may also identify treatments that are more effective with a specific histology such as the chromophobe or hybrid tumours most often seen in BHD.
- Scosyrev E, Messing EM, Sylvester R, Campbell S, Van Poppel H. Renal function after nephron-sparing surgery versus radical nephrectomy: results from EORTC randomized trial 30904. Eur Urol. 2014 Feb;65(2):372-7. PubMed PMID: 23850254.
- Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, Colombel M, Klotz L, Skinner E, Keane T, Marreaud S, Collette S, Sylvester R. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol. 2011 Apr;59(4):543-52. PubMed PMID: 21186077.