“Recently, several robust biomarkers on different molecular levels have been identified which are significantly associated with metastatic risk. These markers, mainly signatures or combination of markers, can be defined in primary tumors to predict the risk of metastasis based on the individual biological background,” said Prof. Dr. Kerstin Junker of the Clinic of Urology and Pediatric Urology at Saarland University Homburg/Saar (DE).

Junker, also the current chair of the EAU Section of Urological Research (ESUR), will speak on the issue of potential biomarkers for decision-making at the 9th European Multidisciplinary Meeting on Urological Cancers (EMUC17) to be held in Barcelona from November 16 to 19. EMUC is annually organised by three of Europe’s leading and specialised medical associations- the European Society for Medical Oncology (ESMO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Association of Urology (EAU).

Renal cell carcinomas (RCC) account for more than 90% of renal tumours. RCC are subdivided into histologically defined subtypes, and the most common subtypes are clear cell RCC (70-75%), papillary RCC (10-15%), chromophobe RCC (5%) and the benign oncocytomas. Junker said genetic analyses have confirmed that these subtypes are characterized by different chromosomal alterations which suggest that each subtype represents a distinct tumour entity with different tumour biology.

Junker said these have implications for daily clinical routine since it has been shown by many clinical researches that the treatment and survival prospects of patients with renal cell tumours depend on the subtype. Patients with clear cell RCC have the worst prognosis compared to other RCC subtypes based on the high frequency of distant metastases.

“Biomarkers will improve the possibility to define the prognosis on a more individual level. But we have to validate these highly potential markers in clinical trials as we are doing it for new therapeutics,” explained Junker.

To identify the most efficient strategy, Junker said doctors have to consider the histological subtype.  “Today, we have more than 15 subtypes which are clearly associated with a specific genetic background on one hand and with different prognosis on the other hand. In addition, based on a specific molecular background, systemic and especially targeted therapies should be selected considering the subtype,” she added.

Asked if she anticipates key breakthroughs in the field of RCC therapy, Junker said:

“I am convinced that we will see a breakthrough progress in the next few years. The understanding of cellular and molecular processes involved in tumour development and especially in tumour progression and metastasis in general, but also in each tumour and tumour subtype will increase the therapeutic options.”

She noted that specialists should understand and consider the inter-tumour heterogeneity as an essential step to individualize therapy based on biomarkers and to identify new targets.  “In addition, we learned that not only tumour cells but also the tumour microenvironment (or tumour stroma) including fibroblasts, endothelial cells and immune cells are important players in tumorigenesis and should be used for biomarker discovery and therapy targets,” said Junker.

Adding depth to MDT

With regards multidisciplinary team (MDT) approaches, Junker noted that specialists from different fields are playing a crucial role in optimal patient care.

“Besides the interdisciplinary approach that includes different medical disciplines, molecular pathology and molecular biology should be more involved in multidisciplinary decision-making. Several university hospitals established interdisciplinary molecular tumour boards, which is one of the steps in this direction,” she said.

EMUC, as a scientific and educational platform for European urological cancer specialists, can achieve much more in boosting knowledge and professional exchanges. Nearing its first decade of active networking, the event helps create a more responsive community of cancer experts. “Such meetings are beneficial because they present an interdisciplinary view on specific urological tumour diseases including not only standard therapy recommendations but also modern knowledge about future directions,” Junker said.

Regarding her expectations on kidney cancer therapies, Junker reiterated her optimism. “I expect that we will use biomarkers routinely to sub-classify tumors and to select the best therapeutic option. This will improve the so called “personalized medicine,” not only to select the most effective therapy, but also to decide if an invasive therapy is necessary at all.”

The three-day EMUC17 presents a compact Scientific Programme that will cover a range of key issues in prostate, kidney and bladders cancers. EMUC will be preceded on 16 November with the EMUC Symposium on Genitourinary Pathology and Molecular Diagnostics (ESUP), the 6th Meeting of the EAU Section of Urological Imaging (ESUI17) and European School of Urology (ESU) Courses. Besides courses and Hands-on Training sessions, ESTRO is organising a delineation contouring workshop with the topic “Target volume contouring in bladder cancer.” A Uropathology Training Workshop will also be held for participants to gain practical insights on uropathology procedures.

For additional details, check the Scientific Programme, Registration and other meeting information pages in this website.

This article was first published on uroweb.

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“Treatment outcomes strongly depend on several pre-treatment factors at presentation as well on the choice of the right treatment for the right patient,” said Dr. Sara M Falzarano, Genitourinary Pathology Fellow at the Robert J. Tomsich Pathology & Laboratory Medicine Institute at the Cleveland Clinic (USA)*.

“In upper tract urothelial carcinoma (UTUC), risk assessment is extremely important and includes evaluation of risk factors,” said Falzarano, one of the discussants and resource speakers at the 9^th European Multidisciplinary congress on Urological Cancers (EMUC17) to be held in Barcelona from November 16 to 19.

A multidisciplinary congress, EMUC provides a platform for onco-urological experts and is now on its ninth edition of gathering leading opinion leaders, researchers and cancer specialists to critically examine treatment strategies for urological malignancies. The event is annually organised by three of Europe’s leading and specialised medical associations- the European Society for Medical Oncology (ESMO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Association of Urology (EAU).

Upper urinary tract (ureter and renal pelvis) disease represents about 5% of urothelial carcinoma at initial diagnosis, the remaining predominantly occurring in the lower urinary tract (bladder and urethra).

“Compared with bladder urothelial carcinoma, patients with UTUC generally are reported to harbour higher grade and stage disease at presentation, with a worse overall prognosis. Since many patients are asymptomatic, early diagnosis can be challenging. Delays from presentation to treatment may represent a concrete issue,” explained Falzarano.

A combination of imaging modalities and pathologic confirmation is required to diagnose UTUC, and the data obtained are essential for risk assessment to identify the best treatment option. The current gold standard surgical management of invasive high-grade UTUC is radical nephroureterectomy (RNU), although kidney-sparing approaches might be indicated in non-invasive low-risk disease, distal ureteric tumours amenable for segmental ureteric resection, and other special circumstances such as solitary (anatomically or functionally) upper urinary tract (due to prior nephrectomy for contralateral urothelial carcinoma, or other reasons).

Challenges in diagnostic staging
Regarding disease progression and survival, the strongest prognostic indicator in UTUC is the level of tumour spread at presentation. “However, accurate pre-operative pathologic staging of UTUC is challenging due to limitations of the biopsy specimen and the fact that it often does not allow for accurate assessment of the depth of invasion of the tumour into the upper urinary tract wall,” noted Falzarano.

After risk assessment, Falzarano pointed out that a consequent choice of the most appropriate therapeutic modality (open/laparoscopic surgery, radical/segmental resection, endoscopic management, neoadjuvant and adjuvant chemotherapy, etc.) has an essential role in achieving optimal treatment outcomes.

These challenges in the diagnosis and management of UTUC cases, she said, underscore the importance of an efficient multidisciplinary team (MDT) approach.

“The communication between members of the team is essential in achieving the best outcome. Discussion and presentation of the different aspects (clinical evaluation, imaging, pathology, etc.) of cases at multidisciplinary tumour boards with integration of professional expertise is a great example of an increasingly implemented strategy to improve multidisciplinary approach,” said Falzarano. She added that appropriate use of electronic medical records and granting the availability of essential patient information in a timely manner to all professionals involved in patient management is another crucial aspect for MDTs.

The EMUC, as an annual international platform for knowledge exchange and discussion of best practices fulfils a meaningful role among urological cancer experts, according to Falzarano.

“Consultative meetings create the invaluable educational opportunity by bringing together the expertise of professionals from different countries and practices to achieve a better picture of the state-of-the-art in the different management areas of a certain disease,” she said. A wider exchange of novel and potential breakthroughs and discoveries in the field can help foster in-depth knowledge, helping doctors provide high-quality care, she added.

The EMUC’s main Scientific Programme will be preceded on 16 November with the EMUC Symposium on Genitourinary Pathology and Molecular Diagnostics (ESUP), the 6th Meeting of the EAU Section of Urological Imaging (ESUI17) and European School of Urology (ESU) Courses. Besides the ESU course and Hands-on Training sessions, ESTRO is organising a delineation contouring workshop with the topic “Target volume contouring in bladder cancer.” A Uropathology Training Workshop will also be held for participants to gain practical insights on uropathology procedures.

*Falzarano will take on the role of Assistant Professor of Pathology at the University of Florida in October this year.

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