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On-Treatment Modified Glasgow Prognostic Score Provides Predictive Information Complementary to Radiological Staging in Metastatic Urothelial Carcinoma on Immunotherapy - Beyond the Abstract

The treatment landscape for metastatic urothelial cancer (mUC) has progressed significantly, especially with the introduction of immune checkpoint inhibitors (ICI). While ICIs have shown promising results, monitoring their effectiveness through standard radiographic staging is complex, particularly for patients with mixed responses or stable disease (SD), who represent a diverse range of outcomes.2

A recent development in this field is the use of the on-treatment modified Glasgow prognostic score (mGPS), which is based on serum C-reactive protein (CRP) and albumin levels. This simple score is an effective tool for prognostication in diverse oncological and non-oncological scenarios, e.g. it outperforms the IMDC score for prognostication of patients with metastatic renal cell carcinoma (mRCC).3 In addition, its longitudinal assessment has been shown to be effective in improving outcome prediction in addition to radiological staging for patients with mRCC treated with ICI.4

However, the application of on-treatment mGPS in mUC patients has not been explored. To address this, we examined data from the IMvigor210 and IMvigor211 trials, accessible through vivli.org. These trials studied the efficacy of atezolizumab, an anti-PD-L1 antibody, in mUC patients. Our analysis involved a post hoc examination of these trials, with a focus on understanding the prognostic value of mGPS when applied to mUC patients undergoing ICI treatment.

Our findings revealed that assessing simple blood biomarkers such as mGPS, LDH, hemoglobin, and neutrophil-to-lymphocyte ratio (NLR) at the time of first radiological staging has significant prognostic value. Specifically, on-treatment mGPS was found to be the most accurate in predicting outcomes of ICI. It improves outcome prediction, especially in patients with SD and progressive disease (PD). Clinically meaningful differences in 12-month survival rates were observed between low-risk and high-risk mGPS patients, who achieved SD on ICI.

Moreover, on-treatment mGPS emerged as an independent predictor of outcomes in both trials, even when adjusting for various risk factors, such as Bellmunt risk factors. This highlights the potential of integrating mGPS into clinical practice to enhance outcome predictions complementary to radiological assessments.

The use of on-treatment mGPS offers a more comprehensive evaluation of a patient's general health, reflecting chronic inflammation and tumor burden. This method could be particularly beneficial in ambiguous cases such as atypical responses or oligoprogressive disease stages. By assessing mGPS early on-treatment, physicians might be able to receive information on treatment response before radiological staging. In IMvigor210 here, we have shown that mGPS provides valuable information after only 6 weeks, which is 4-6 weeks prior to first standard radiological staging.

However, our study is not without limitations. The primary constraint is that our analysis was based on post hoc data and solely focused on patients treated with atezolizumab. Future research should aim to validate the use of on-treatment mGPS across different ICIs, also for patients receiving combination with ICI (e.g. Enfortumab vedotin + Pembrolizumab) and in various treatment settings.

In conclusion, our study underscores the value of on-treatment mGPS as a dynamic, cost-effective inflammatory biomarker for enhancing outcome prediction alongside radiological staging in patients with mUC undergoing immunotherapy.

Written by: Jonas Saal,1 Viktor Grünwald,2 Tobias Bald,3 Manuel Ritter,4 Peter Brossart,5 Yoshihiko Tomita,6 Arndt Hartmann,7 Michael Hölzel,3 Markus Eckstein,7 Niklas Klümper8

  1. Medical Clinic III for Oncology, Hematology, Immune-Oncology and Rheumatology, University Medical Center Bonn, Bonn, Germany; Institute of Experimental Oncology, University Medical Center Bonn, Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Bonn, Germany.
  2. Interdisciplinary Genitourinary Oncology, West-German Cancer Center, Essen University Hospital, Essen, Germany.
  3. Institute of Experimental Oncology, University Medical Center Bonn, Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Bonn, Germany.
  4. Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Bonn, Germany; Department of Urology and Pediatric Urology, University Medical Center Bonn, Bonn, Germany.
  5. Medical Clinic III for Oncology, Hematology, Immune-Oncology and Rheumatology, University Medical Center Bonn, Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Bonn, Germany.
  6. Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
  7. Comprehensive Cancer Center EMN, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Bavarian Cancer Research Center, Erlangen, Germany.
  8. Institute of Experimental Oncology, University Medical Center Bonn, Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Bonn, Germany; Department of Urology and Pediatric Urology, University Medical Center Bonn, Bonn, Germany.
References:

  1. Saal J, Grünwald V, Bald T, Ritter M, Brossart P, Tomita Y, et al. On-treatment Modified Glasgow Prognostic Score Provides Predictive Information Complementary to Radiological Staging in Metastatic Urothelial Carcinoma on Immunotherapy. Eur Urol Oncol. 2023 Nov 22;S2588-9311(23)00250-X.
  2. Luo J, Wu S, Rizvi H, Zhang Q, Egger JV, Osorio JC, et al. Deciphering radiological stable disease to immune checkpoint inhibitors. Annals of Oncology [Internet]. 2022 May [cited 2022 May 23];S0923753422011401.
  3. Saal J, Bald T, Hölzel M, Ritter M, Brossart P, Ellinger J, et al. In the phase 3 IMmotion151 trial of metastatic renal cell carcinoma the easy-to-implement modified Glasgow prognostic score predicts outcome more accurately than the IMDC score. Ann Oncol. 2022 Jun 15;S0923-7534(22)01730-6.
  4. Saal J, Bald T, Eckstein M, Ralser DJ, Ritter M, Brossart P, et al. Integrating On-Treatment Modified Glasgow Prognostic Score and Imaging to Predict Response and Outcomes in Metastatic Renal Cell Carcinoma. JAMA Oncol. 2023 Jun 22
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