A novel model that incorporates certain radiologic findings may improve identification of patients with metastatic renal cell carcinoma (mRCC) who could benefit from cytoreductive nephrectomy (CN), according to investigators.
“Currently, radiographic findings are discussed and used to make decisions in multidisciplinary meetings, but large studies have not evaluated the prognostic value of common radiologic features such as metastatic tumor burden, location of metastasis or the number of metastatic sites,” said E. Jason Abel, MD, chief of urologic oncology and professor of urology and radiology at the University of Wisconsin School of Medicine and Public Health in Madison.
Dr Abel and colleagues have developed the Selection for Cytoreductive Nephrectomy Score (SCREEN) to improve selection for CN by identifying patients least likely to die within the first year after the procedure. The SCREEN model used data from consecutive patients with mRCC treated with upfront CN at 5 institutions (University of Wisconsin in Madison, Emory University in Atlanta, Georgia, Moffitt Cancer Center in Tampa, Florida, Penn State Milton S. Hershey Medical Center in Hershey, Pennsylvania, and The University of Texas MD Anderson Cancer Center in Houston) between 2006 and 2017. The model was compared with the International Metastatic RCC Database Consortium (IMDC) model for predictive accuracy and clinical usefulness.
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To develop the model, the investigators studied 914 patients with mRCC who were treated with upfront CN and had not received preoperative systemic therapy. The team factored in 7 independently predictive variables (3 or more metastatic sites, total metastatic tumor burden of 5 cm, bone metastasis, systemic symptoms, low serum hemoglobin, low serum albumin, and a neutrophil/lymphocyte ratio of 4 or higher). Patients had a median follow-up of 42.7 months.
The SCREEN score demonstrated higher predictive accuracy for first-year mortality compared with the IMDC model, with an area under the receiver operating characteristic curve of 0.76 vs 0.55, the investigators reported in European Urology Oncology. The authors noted that all patients treated with CN had synchronous mRCC, which is associated with significantly worse survival than for metachronous mRCC. Current decision-making, however, is based on mRCC populations with primarily metachronous disease, the authors noted.
On multivariable analysis, systemic symptoms independently predicted a 1.3-fold increased risk of first-year mortality. The presence of 3 or more metastatic sties, a total metastatic tumor burden of 5 cm or more, bone metastases, low serum hemoglobin levels, low serum albumin levels, and a neutrophil/lymphocyte ratio higher than 4 independently predicted a 1.9-, 1.3-, 1.3-, 1.4-, 1.4-, and 1.3-fold increased risk of first-year mortality, respectively.
Using the IMDC model, 34 patients (6%) were classified as favorable, 333 patients (62%) were classified as intermediate, and 167 patients (32%) of patients were classified as having poor risk. According to the SCREEN model, 132 patients (25%) were classified as having a favorable risk, 256 patients (48%) were classified as intermediate risk and 148 patients (27%) were classified as having poor risk.
There was no difference in survival among the 5 centers for IMDC intermediate- or poor-risk patients, suggesting that selection criteria and treatment were similar among the centers, Dr Abel said. “Radiographic criteria improved the ability to define a cohort of patients who were poor risk and unlikely to benefit from upfront surgery,” he said. “The poor-risk patients had more than 11-fold risk of first-year mortality compared to the favorable risk per the SCREEN score.”
Further validation of The SCREEN model using independent cohorts of patients is warranted. As the treatment paradigm continues to evolve with more effective systemic therapies, it may be crucial to modify and improve existing prognostic models that are used to guide treatment decisions. “We believe the SCREEN model can be used for future studies to define the optimal role and timing of surgery for mRCC patients,” Dr Abel said.
Gary Steinberg, MD, professor of urology and a urologic oncologist at RUSH University Medical Center in Chicago, Illinois, pointed out that the significance of CN has changed, with patients increasingly receiving systemic therapy upfront. “Moreover, the addition of radiological criteria to the stratification criteria is subjective and based on surgical skill and experience rather than the intrinsic nature of the individual’s cancer,” Dr Steinberg said.
Retrospective series have limited generalizable information, due to inherent biases, such as missing data and patients lost to follow-up, he noted. The paper would have been strengthened by outlining the morbidity and mortality of CN (as there were 18 perioperative deaths not included in the analysis) as well as the perioperative and intraoperative surgical decision-making, Dr Steinberg said.
Rohith Arcot, MD, a urologic surgical oncologist at Ochsner MD Anderson Cancer Center in Jefferson, Louisiana, said the new study is remarkable because it highlights the real-world limitations in determining the role of CN. “At present, the SCREEN tool sets a framework for discussing the role of cytoreductive nephrectomy for individual patients during any multidisciplinary team meeting but does not answer the critical question of timing of cytoreductive nephrectomy as a part of the systemic treatment for mRCC,” Dr Arcot said.
The SCREEN tool helps identify potential candidates for CN, but not the timing of the operation (before or after systemic therapy), and questions remain regarding morbidity and mortality associated with the procedure, Dr Arcot said. “Studies like this continue to be the first steps in the immunotherapy era to help us answer the many existing questions regarding surgery as a part of the treatment landscape for synchronous metastatic renal cell carcinoma,” he said.
Riccardo Autorino, MD, PhD, professor of urology and the Director of Surgical Innovation & Clinical Research in the Department of Urology at Rush University Medical Center in Chicago, said the current analysis was well conducted and performed on a large dataset. However, it still has limitations, mostly related to the retrospective nature of the study design. “The tools currently used in the guidelines (IMDC and MSKCC criteria) to determine which patient should get an upfront cytoreductive nephrectomy are limited and suboptimal,” he said. “Therefore, studies like this are important. On the other hand, research in this area is also difficult as systemic therapies for metastatic kidney cancer are rapidly changing so that the landscape is also constantly changing.”
Reference
Abel EJ, Master VA, Spiess PE, et al. The Selection for Cytoreductive Nephrectomy (SCREEN) Score: Improving surgical risk stratification by integrating common radiographic features. Eur Urol Oncol. Published online July 11, 2023. doi:10.1016/j.euo.2023.06.008
