The Complex and Nuanced Care for Early-stage Testicular Cancer: Lessons from the European Association of Urology and American Urological Association Testis Cancer Guidelines - Beyond the Abstract

The majority of patients with testicular germ cell tumors (GCT) present with early-stage disease limited to the testis and retroperitoneum (clinical stage I-IIB). Patients with early-stage GCT have remarkably favorable outcomes with cure rates >98%. In light of this, the management of these young patients is incredibly complex. Clinicians are faced with the difficulty of deciding among adjuvant treatment strategies for these patients, which may include surveillance (preferred for stage IA disease), retroperitoneal lymph node dissection (RPLND), chemotherapy, or, in the case of seminoma, radiotherapy. Several risk factors associated with more aggressive features or an increased risk of relapse have been identified to help inform active therapeutic strategies. Furthermore, both the European Association of Urology (EAU) and the American Urological Association (AUA) have published guidelines to help guide clinicians in managing early-stage GCT.1,2 In our editorial,3 we compare and contrast the guideline statements from the EAU and AUA in this clinical space, including statements related to screening, diagnostic evaluation, orchiectomy, germ cell neoplasia in situ, management of seminoma, management of stage I non-seminoma (NSGCT), and management of stage IIA/IIB NSGCT. In particular, we highlight the nuanced and controversial clinical scenarios for which clinical care may be improved.


Indeed, both sets of guidelines recognize the priority of balancing cancer control for this curable disease with minimizing morbidity related to overtreatment. Both suggest short-interval repeat testing in the setting of equivocal radiographic findings and normal serum tumor markers (STM), and both promote surveillance strategies for early-stage I disease. However, the EAU and AUA guidelines tend to diverge in their recommended approaches to managing higher-risk disease.  As an example, there is a considerable discrepancy between the two guidelines on the role of RPLND for treating high-risk stage I NSGCT. We speculate that these discrepancies likely stem from inherent philosophical and cultural differences in population-level and individual patient concerns in striking the appropriate balance between minimizing overtreatment and long-term toxicity versus avoiding undertreatment and risks of relapse and mortality.3

We also highlight the role that emerging serum biomarkers may play in further guiding clinicians in managing patients with early-stage GCT.  Recognizing the limitations in both the sensitivity and specificity of conventional STMs (α-fetoprotein, ß-human chorionic gonadotropin, and lactate dehydrogenase), we recently found that serum microRNA levels—particularly miR-371a-3p—can accurately differentiate small-volume viable GCT from benign processes or teratoma in early-stage, chemotherapy-naïve patients with negative STMs undergoing primary RPLND.4 This study builds off a mounting body of evidence that reveals microRNAs as a promising basis to implement precision medicine strategies in treating patients with early-stage GCT.5 If validated, they will likely play a critical role in this space for better patient selection, regardless of treatment approach.

Written by: Nirmish Singla, MD, MSCS and Aditya Bagrodia, MD, Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas

References:

  1. Albers, Peter, Walter Albrecht, Ferran Algaba, Carsten Bokemeyer, Gabriella Cohn-Cedermark, Karim Fizazi, Alan Horwich, Maria Pilar Laguna, Nicola Nicolai, and Jan Oldenburg. "Guidelines on testicular cancer: 2015 update." European urology 68, no. 6 (2015): 1054-1068.
  2. Stephenson, Andrew, Scott E. Eggener, Eric B. Bass, David M. Chelnick, Siamak Daneshmand, Darren Feldman, Timothy Gilligan et al. "Diagnosis and treatment of early stage testicular cancer: AUA guideline." The Journal of urology 202, no. 2 (2019): 272-281.
  3. Bagrodia, Aditya, Phillip Pierorazio, Nirmish Singla, and Peter Albers. "The Complex and Nuanced Care for Early-stage Testicular Cancer: Lessons from the European Association of Urology and American Urological Association Testis Cancer Guidelines." (2019).
  4. Lafin, John T., Nirmish Singla, Solomon L. Woldu, Yair Lotan, Cheryl M. Lewis, Kuntal Majmudar, Anna Savelyeva et al. "Serum MicroRNA-371a-3p Levels Predict Viable Germ Cell Tumor in Chemotherapy-naïve Patients Undergoing Retroperitoneal Lymph Node Dissection." European urology 77, no. 2 (2020): 290.
  5. Singla, Nirmish, John T. Lafin, and Aditya Bagrodia. "MicroRNAs: Turning the Tide in Testicular Cancer." (2019).
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