AUA 2024: Comprehensive Evaluation of Response to Immune Checkpoint Blockade in Primary Tumor: Radiographic and Radiomic Features Predict Pathologic Response in Primary Tumor

( On the first day of the annual American Urological Association (AUA) meeting in San Antonio, Dr. Mark Dawidek and colleagues shared an insightful presentation on the evaluation of primary tumor response to immune checkpoint blockade, or ICB. Despite the promise of ICB (alone or in combination with other therapies) in the treatment of metastatic renal cell carcinoma, existing literature lacks sufficient understanding of how biomarkers may predict ICB response. To this end, Dr. Dawidek and his team at Memorial Sloan Kettering Cancer Center sought to explore such biomarkers and their association with ICB response.

For patients with renal cell carcinoma (RCC), about 1/3rd will have metastatic disease at the time of diagnosis1. Host defenses have been suspected to play a role in disease development and progression, stemming from spontaneous regression of disease, prolonged stability without progression, and late relapses following nephrectomy2. During an immune response, various regulatory checkpoints are initiated that inhibit full T-cell activation. This usually protects host cells from autoimmune responses but may lead to cancer proliferation. Such activation and subsequent effector functions require two signals; current ICB agents work to block coinhibitory molecules that will allow for T cell effector functions and antitumor response3. Therefore, ICB has offered a revolutionary treatment for these patients.

A retrospective study was conducted, ultimately identifying 185 patients with a diagnosis of metastatic renal cell carcinoma who received systemic immune checkpoint blockade (IO/IO or IO/TKI), wherein 62 of these patients had a primary kidney tumor present. This group was further divided into two non-mutually exclusive cohorts (Figure 2). Cohort A included 50 patients who underwent pre-ICB CT scans and at least 1 post-ICB CT scan, while Cohort B included 31 patients with a pre-ICB CT scan, post-ICB/pre-operative CT scan, and final pathology evaluation of the residual viable tumor. Over a follow-up period of 24 months, radiographic, clinical, and pathologic data was recorded. Metrics such as the time from initial treatment through treatment failure, second-line therapy/surgical intervention, radiographic kinetic response, RECIST measurements, and other radiomic features were captured.Assessment for Eligibility and Cohort Enrollment
Overall, ICB therapy response varied with four potential outcomes in metastatic/primary pairs. At 3 months, response to metastatic and primary lesions predicted time-to-next therapy, as well as overall survival. For both primary and metastatic disease, shrinkage correlated to optimal clinical outcomes, while progression was associated with poorer results. Moreover, the depth of response for primary tumor is associated with time-to-next therapy and overall survival, with response < 75% at 3 months being ideal for the best outcomes, with both outcomes of high significance (p<0.01). Dr. Dawidek noted that this may be due to underlying tumor heterogeneity.

There was some discrepancy between radiographic tumor volume and pathologic viable tumor volume (interclass correlation coefficient = 0.20). As such, preoperative volume may overestimate the pathologic tumor volume resulting in a mean difference of 622 cm3 (95% CI: 285, 958). Pathologic viable tumor volume is also associated with contrast enhancement in pre-operative radiographic studies and change in contrast enhancement (Spearman correlation coefficient p=0.41, p=0.02). In the further evaluation of radiomic features of systemic therapy responses, first-order and second-order elements can identify patients with minimal residual disease on pathologic evaluation. All findings are further summarized below in Figure 2.Cohort A and B Post-ICB Findings 
Following his presentation, discussion moderator Dr. Sarah Pstuka inquired about how their findings may be applied to clinical practice. Dr. Dawidek stated, “We would be most interested in getting a sense of which patients we expected to have a discrepancy and minimal residual disease in their primary tumor, who may not have a similar response in their peripheral site.”

Moderator Dr. Federico Belladelli then raised a question concerning the inconsistency between the radiological and pathological assessments, inquiring about the rationale behind this variance, to which Dr. Dawidek replied, “This has been relatively commonly described in the context of immunotherapy, therefore it can be quite challenging to resist additional measures of response. Often issues like pseudo-progression are overestimating the volume of residual disease.”

In conclusion, Dr. Dawidek et al. illuminated the promise that ICB therapy may offer, concerning the management of metastatic renal cell carcinoma. He concluded his presentation with the following messages for the audience:

  • In sum, radiographic response for primary tumor can predict time to next treatment and overall survival in Cohort A. Interactions between the observed response of both primary and metastatic tumors can further provide insight into clinical outcomes.
  • In Cohort B, residual viable tumors may be overestimated when standard volume-based radiographic assessments are employed.
  • Furthermore, contrast enhancement and other radiographic features from the primary tumor can offer additional insight into the residual viable tumor.
  • Non-invasive radiologic characterization demonstrates promise for guiding post-ICB therapy management, including cytoreductive surgery.

Presented by: Mark Dawidek, MD, Memorial Sloan Kettering Cancer Center, New York City, New York

Written by: Mariah Hernandez, Junior Research Specialist, Department of Urology, University of California, Irvine, Irvine, CA@mariahch00 on Twitter during the 2024 40th American Urological Association (AUA) Annual Meeting, May 3 — May 6, 2024, San Antonio, Texasthe 2024 40th American Urological Association (AUA) Annual Meeting, May 3 — May 6, 2024, San Antonio, Texas

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