He first began with a discussion of cytoreductive nephrectomy, the underlying rationale for which has been supported in other cancers such as breast and ovarian cancers. There has been much debate in the field about the role of cytoreductive nephrectomy in advanced renal cell carcinoma (aRCC). Dr. Singer showed data from a systematic review published in 2019 (https://doi.org/10.1016/j.eururo.2018.09.016) highlighting that multiple observational studies suggest a benefit for cytoreductive nephrectomy, but the CARMENA randomized clinical trial did not show a similar benefit.
This holds true for non-clear cell RCC observational studies, where there are no randomized prospective studies,
As well as in the immunotherapy era (https://doi.org/10.1016/j.urolonc.2020.02.029) based on studies where patients first received cytoreductive nephrectomy then systemic immunotherapy.
Several randomized trials that are ongoing will help clarify the role of cytoreductive nephrectomy in aRCC, including PROBE, NORDIC-SUN, and Cyto-KIK.
Dr. Singer then shifted to discussing the potential advantage of metastasectomy. Multiple considerations must be taken into account when deciding about metastasectomy. From a patient perspective, risk stratification, performance status, nutritional status, and frailty are factors to consider. From a tumor perspective, histology, grade, ability to achieve complete surgical resection, and the absence of hepatic, brain, or bone metastases should be considered. Patients who are able to have a complete metastasectomy have been shown to have significantly improved overall survival relative to matched controls in multiple retrospective datasets (https://doi.org/10.1016/j.urolonc.2020.07.021). Regarding surgical risk, this study showed that age greater than 65 or brain metastasis was associated with increased risk of mortality with metastasectomy. The benefit from complete resection of metastases holds true regardless of whether this was done in the targeted therapy era or more modern immunotherapy era.
Next, Dr. Singer transitioned to talking about the role of radiation therapy in aRCC. Lower volume metastatic disease can be treated successfully with stereotactic ablative radiation therapy (SABR), and patients with just 1 metastatic site are able to remain free of systemic therapy longer than patients with 2-4 metastatic sites. Other factors associated with longer freedom from systemic therapy in aRCC include clear cell histology, favorable risk stratification, and absence of bony metastases.
There is data examining the combination of radiotherapy with immunotherapy in aRCC. For example, one paper (https://doi.org/10.1111/bju.15284) evaluated the safety of stereotactic radiotherapy in aRCC patients receiving either immunotherapy or targeted therapy. In this small study, overall and progression-free survival was improved with this approach in patients with less than 5 metastatic sites and better ECOG performance status. Many trials are ongoing to understand the role of radiotherapy in aRCC, including helping define a definition of oligometastatic disease.
Dr. Singer concluded that surgery and radiotherapy have a role in aRCC, typically for patients with good performance status, limited metastatic disease burden in certain states, but the optimal timing along with systemic therapy continues to require further investigation.
Presented by: Eric A. Singer, MD, FASCO, FACS, MA, MS, Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Jersey
Written by: Alok Tewari, MD, Ph.D., Medical Oncologist at the Dana-Farber Cancer Institute, at the virtual 2021 American Society of Clinical Oncology Annual Meeting Congress (#ASCO21), June 4th-June 8th, 2021