While some patients with metastatic renal cell carcinoma (mRCC) may experience an indolent disease progression and could benefit from deferred systemic therapy (ST), including active surveillance (AS) or metastasis-directed therapy (MDT), the evidence on its oncological efficacy and safety are still not well-established. We aimed to provide an overview of the available evidence on oncological outcomes of patients with mRCC undergoing deferred ST.
A systematic review of the literature was conducted in August 2024 using the PubMed, Scopus, and Embase databases to identify prospective and retrospective studies evaluating AS or deferred ST for patients with mRCC (PROSPERO ID: CRD42024579021). The co-primary outcomes were ST-free survival (ST-FS) and overall survival (OS). A random-effects model was used for quantitative analysis.
We identified 15 eligible studies including 2,912 patients. Of these, 4 were prospective (n = 589 patients) and 11 were retrospective (n = 2,323 patients). The estimated 1-, 2-, 3-, 4-, and 5-year ST-FS rates (n = 1,070) were 74%, 54%, 49%, 43%, and 37%, respectively. The estimated 1-, 2-, 3-, 4-, and 5-year OS rates (n = 2,872) were 96%, 89%, 80%, 71%, and 69%, respectively. Key limitations at a study-level included selection bias, unmeasured confounding, and variability across deferred ST/AS protocols, including the indications for metastasis-directed therapy. Moreover, most studies used tyrosine kinase inhibitors as ST. The proportion of patients receiving MDT, including metastasectomy or stereotactic body radiation therapy, ranged from 14 to 100%.
Deferring ST by AS or MDT was associated with favorable oncological outcomes in carefully-selected patients with mRCC, highlighting the potential value of this approach in the contemporary multidisciplinary management of mRCC. Considering the limitations of available evidence and the lack of data on the oncological efficacy and safety of deferred ST for mRCC in the immune-oncology era, our review calls for further research in this field.
Urologic oncology. 2025 Dec 12 [Epub ahead of print]
Ichiro Tsuboi, Pawel Rajwa, Marcin Miszczyk, Tamás Fazekas, Akihiro Matsukawa, Mehdi Kardoust Parizi, Robert Schulz, Stefano Mancon, Ekaterina Laukhtina, Tatsushi Kawada, Satoshi Katayama, Takehiro Iwata, Kensuke Bekku, Koichiro Wada, Pierre I Karakiewicz, Piotr Chlosta, Motoo Araki, Shahrokh F Shariat, Riccardo Campi
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland; Division of Surgery and Interventional Science, University College London, London, UK., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Collegium Medicum - Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Semmelweis University, Budapest, Hungary., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Quebec, Canada., Department of Urology, Jagiellonian University, Medical College, Krakow, Poland., Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Semmelweis University, Budapest, Hungary; Department of Urology, Jagiellonian University, Medical College, Krakow, Poland; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czechia; Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Research Center for Evidence Medicine, Urology Department Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: ., Unit of Urology and Renal Transplantation, Careggi Hospital, University of Florence, Florence; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; European Association of Urology (EAU) Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, the Netherlands.