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MOLECULAR BIOMARKERS IN UROLOGIC ONCOLOGY: ICUD-WUOF CONSULTATION

Personalized Medicine in Urologic Oncology
Yair Lotan,1 Jack Schalken,2 Nathan Lawrentschuk,3,4

1 Department of Urology, University of Texas Southwestern Medical Center Dallas, United States, 2 Department of Urology, Radboud University Medical Center,  
Nijmegen, The Netherlands, 3 Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia,  
4 Department of Urology, Royal Melbourne Hospital, Australia

Soc Int Urol J. 2020;1(1):6–7

In an ideal world, the diagnosis and treatment of disease would be non-invasive and precise. Biologic testing 
would be performed using easily available samples such as blood, urine, sputum, and skin swab, which would 
provide information regarding the cause of a disease as well as prognosis and optimal treatment. Although 
in some areas there has been progress toward these goals, in others, significant work must still be done before 
molecular markers can be incorporated into common practice. In 2019, the Société Internationale d’Urologie 
(SIU), the International Consultation on Urological Diseases (ICUD) and the World Urologic Oncology 
Forum (WUOF) convened key opinion leaders from around the world to review the current use of molecular 
markers for the diagnosis and management of urologic malignancies, as well as developments in research.  
This special edition of the SIUJ presents a summary of their work.

An ideal marker would fulfill strict criteria demonstrating that it provides clinical benefit, information that is 
independent from other clinical factors, cost-effectiveness, and reproducibility, and would be comprehensively 
validated. The pathway to incorporate molecular markers should be standardized, similar to that required for 
approval of medications. A marker should pass through several phases, as outlined by Melissa Assel and Andrew 
Vickers [1], in which it is tested against the clinical question that it is supposed to answer and should then be validated 
in multicenter prospective cohorts. Many markers do not survive the initial phase of discovery and evaluation in small 
retrospective cohorts. This phase, while exciting, is subject to risk of bias and overfitting. If a marker is developed 
that shows promise, the next phase of evaluation should involve validation in independent cohorts. Finally, a test of 
clinical utility should be performed on a prospective cohort in which the marker is evaluated for its ability to change 
clinical management to the benefit of the patient.

In this issue of the SIUJ, Ankeet Shah and colleagues discuss the sources from which most molecular biomarkers 
are obtained and the considerations that are associated with each [2]. Blood-based markers have had major impact 
in the management of testis and prostate cancer. Diagnosis and management of testis cancer includes the use of 
alpha-fetoprotein and beta-hCG. These markers help in differentiating histology and can guide use of chemotherapy, 
but they have limitations related to sensitivity and specificity. Aditya Bagrodia and colleagues examine the role of 
these markers and new promising markers, especially miRNA, in the management of testicular germ cell tumors [3]. 
Prostate specific antigen, in contrast, was developed for surveillance of patients with prostate cancer but has been 
incorporated into screening programs. The use of PSA for screening has resulted in decades of controversy, since 
evaluation of the impact of prostate cancer screening on survival occurred many years after widespread utilization of 
the marker for this purpose [4]. Renu Eapen and colleagues examine serum-based markers that have been developed 
with the intention of overcoming some of the limitations of PSA [5]. Gillian Vandekerkhove and Alexander Wyatt 
focus specifically on the development of circulating tumor DNA as a clinically useful biomarker for prostate cancer [6].

Urine-based markers have had the biggest impact in the management of bladder cancer. Urine cytology have been 
incorporated into guidelines despite poor sensitivity for low-grade cancer and moderate sensitivity for high-grade 
disease. Other urine markers have not been adopted because of failure to fulfill stringent criteria of performance. In 
this issue of the SIUJ, Tilman Todenhöfer and colleagues review the performance of currently available urine-based 
tumor markers for bladder cancer detection [7], and Laura-Maria Krabbe et al. give an overview of the clinical utility 
of these markers [8]. Similarly, for prostate cancer there are attempts to improve detection using urinary biomarkers, 
and these are reviewed by Renu Eapen and colleagues [5].

The utility of tissue-based markers is limited by the accessibility of tissue. Nonetheless, in specific clinical scenarios 
where tissue is readily available, tissue markers can be invaluable. Peter Lonergan and colleagues [9] report on exciting 
developments in tissue biomarkers for prostate cancer, while Liang Qu and colleagues discuss the utility of tissue 
markers for diagnosis and classification of renal cell carcinoma [10].

http://www.siuj.org
mailto:yair.lotan%40utsouthwestern.edu?subject=SIUJ


7SIUJ.ORG SIUJ  •  Volume 1, Number 1  •  October 2020

Personalized Medicine in Urologic Oncology

The emphasis on achieving a high standard of 
evidence before incorporating markers into clinical 
practice has merit [1]. It is particularly important 
because of the risk associated with false positive results, 
which often lead to unnecessary testing and anxiety. 
Furthermore, these tests may contribute significantly 
to the cost of health care, a worldwide concern. Some 
biomarkers have been adopted without sufficient 
evidence of effectiveness, resulting in controversy.

The Cancer Genome Atlas, which molecularly 
characterized over 11 000 cancers [11], has provided 
important new information regarding urologic cancers, 
that is now being used to characterize tumor behavior, 
prognosis, and response to therapy. This program, 
along with advances in next-generation sequencing 
will advance the goals of personalized medicine, and 
significant effort is needed to interpret this information 
using bioinformatics and to validate its utility in clinical 
care. Multiple new clinical trials are based on targeting 
specific mutations or enriching the patient population 
for the expression of immunological markers such as 

PDL1. Understanding the significance of these molecular 
alterations and how to use them to guide therapy will 
likely take years; performing trials is critical. Patients 
with metastatic disease, especially urothelial cancer, 
have a short life expectancy and do not have the luxury 
of being treated with multiple therapies in an attempt 
to find one that works. Thus, using molecular tests with 
predictive value to identify early the treatment with 
the highest likelihood of response may make a major 
difference for these individuals.

Rapid advances in our understanding of cancer 
biolog y are providing multiple opportunities to 
develop and validate molecular markers that will have 
a profound impact on patient management. The papers 
in this special issue of the SIUJ present information 
on currently available and potential future markers. 
For patients, researchers, and providers seek ing  
to incorporate markers into practice, it is important 
to evaluate how well the markers perform overall  
and whether they can provide a tool that improves 
patients’ care.

References

1. Assel M, Vickers A J. SIU -ICUD Consult ation on Molecular 
Biomarkers in Urological Oncology: Clinical development of 
biomarkers. Soc Int Urol J. 2020;1(1):16–22.

2. Shah A, Grimberg DC, Inman BA. SIU-ICUD Consultation on 
Molecular Biomarkers in Urological Oncology: Classification of 
molecular biomarkers. Soc Int Urol J. 2020;1(1):8–15.

3. Bagrodia A, Daneshmand S, Cheng L, Amatruda J, Murray M, Lafin 
JT. SIU-ICUD Consultation on Molecular Biomarkers in Urological 
Oncology: The past and future of biomarkers in testicular germ cell 
tumors. Soc Int Urol J. 2020;1(1):77–84.

4. PLCO Project Team, Gohagan JK, Prorok PC, Hayes RB, Kramer B-S. 
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening 
Trial of the National Cancer Institute: History, organization, and 
status. Control Clin Trials. 2000;21(6):251S-272S. ht tps://doi.
org/10.1016/S0197-2456(00)00097-0

5. Eapen R, Lonergan PE, Bagguley D, Ong S, Condon B, Meng MV. 
SIU-ICUD Consultation on Molecular Biomarkers in Urological 
Oncology: The clinical applications of serum and urinary biomarkers 
in prostate cancer Soc Int Urol J. 2020;1(1):30–38.

6. Vandekerkhove G, Wyatt AW. SIU-ICUD Consultation on Molecular 
Biomarkers in Urological Oncology: Circulating tumour DNA as a 
biomarker source in metastatic prostate cancer. Soc Int Urol J. 
2020;1(1):39–48.

7. Todenhöfer T, Lodde M, van Kessel K, Pichler R, Vlahou A, Lotan 
Y. SIU-ICUD Consultation on Molecular Biomarkers in Urological 
Oncology: Urinar y-based markers for bladder cancer detection.  
Soc Int Urol J. 2020;1(1):49–61.

8. Krabbe L-M, Gakis G, Lotan Y. SIU-ICUD Consultation on Molecular 
Biomarkers in Urological Oncology: Clinical utility of bladder cancer 
biomarkers. Soc Int Urol J. 2020;1(1):62–67.

9. Lonergan PE, Washington SL III, Meng MV, Eapen R. SIU-ICUD 
Consultation on Molecular Biomarkers in Urological Oncology: 
The clinical applications of tissue biomarkers in prostate cancer.  
Soc Int Urol J. 2020;1(1):23–29.

10. Qu L, Thirugnanasundralingam V, Bolton D, Finelli A, Lawrentschuk 
N. Consultation on Molecular Biomarkers in Urological Oncology: 
Tissue-based immunohistochemical markers for diagnosis and 
classification of renal cell carcinoma Soc Int Urol J. 2020;1(1):68–76.

11. The Cancer Genome Atlas. The National Cancer Institute. Available 
f r om: h t t p s: // w w w.c an c er.gov/ab ou t- n ci/or ganiz a tion /c c g /
research/structural-genomics/tcga. Accessed August 27, 2020.

http://www.siuj.org
https://doi.org/10.1016/S0197-2456(00)00097-0
https://doi.org/10.1016/S0197-2456(00)00097-0
https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga
https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga

