Treatment of residual RCC following first-line systemic therapy

Highlights:

1. Renal cell carcinoma (RCC) often leaves residual disease post-treatment.
2. Tumor heterogeneity complicates RCC management and treatment resistance.
3. Effective strategies include metastasectomy, nephrectomy, and SBRT.
4. Combining surgical, local ablative, and systemic therapies can improve outcomes.
5. Addressing residual disease is crucial for long-term control and survival.

INTRODUCTION

Renal cell carcinoma (RCC) represents approximately 90% of kidney cancer cases, making it the most common type of kidney cancer. The primary subtypes of RCC are clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC), with ccRCC being the predominant subtype, accounting for about 75% of cases. The remaining subtypes are relatively rare^1,2.

Globally, the incidence of RCC has been rising, with an estimated 431,288 new cases in 2020. RCC is the 14th most common cancer worldwide, with higher incidence rates observed in developed regions such as Europe and North America. Men are approximately twice as likely to develop RCC as women, and the incidence increases with age^1,2.

Several risk factors contribute to the development of RCC. The most significant modifiable risk factors include smoking, obesity, and hypertension. Additionally, chronic kidney disease (CKD) and end-stage renal disease (ESRD) are known to increase the risk of RCC. Genetic predispositions, such as von Hippel-Lindau (VHL) syndrome and hereditary leiomyomatosis and RCC (HLRCC), also play a crucial role in the development of this cancer^1,3.

Advances in imaging techniques have led to an increase in the incidental detection of RCC, often before the onset of symptoms. Traditional symptoms, such as hematuria, flank pain, and a palpable mass, are now very seldom observed, occurring in less than 1% of cases, due to early detection through cross-sectional imaging¹.

Prior to 2005, cytokine therapies offered limited benefit for mRCC. The introduction of VEGF TKIs and then ICIs revolutionised treatment, leading to improved survival. Current regimens often combine ICIs, but disease progression remains common, necessitating further research for managing mRCC. Despite the effectiveness of these treatments, a significant number of patients develop residual disease, necessitating further therapeutic strategies. Understanding the biological mechanisms underlying treatment resistance and the management of residual disease is critical for improving patient outcomes⁴.

The objective of this review is to provide a comprehensive analysis of the treatment options and outcomes for residual renal cell carcinoma (RCC) following first-line systemic therapy.

Figure 1. Treatment paradigm for Frontline ccRCC

Tumour Heterogeneity and Importance of Residual Disease

Tumour heterogeneity, characterised by diverse genetic and phenotypic variations within a single tumour, significantly impacts the treatment of RCC. This intratumor heterogeneity fosters tumour adaptation and resistance to therapies, complicating personalised medicine approaches that often rely on single biopsy samples. Residual disease following first-line systemic therapy presents a substantial clinical challenge, as it is frequently comprised of resistant tumour cell subpopulations. These cells can drive disease progression and metastasis, underscoring the necessity of developing effective therapeutic strategies to manage residual RCC and improve patient outcomes​^5,6.

The evolution of clear cell RCC is predominantly characterised by the early loss of chromosome 3p, leading to the inactivation of key tumour suppressor genes such as VHL, PBRM1, SETD2, and BAP1. Distinct evolutionary trajectories have been identified: linear evolution with few driver events, branched evolution with high intratumor heterogeneity (ITH), and punctuated evolution with bursts of multiple mutations. Tumours with low ITH and low genomic instability exhibit low metastatic potential, whereas those with low ITH but high somatic copy-number alterations (SCNAs) show rapid, widespread metastasis⁶.

A decade ago, the study by Gerlinger et al. highlighted the importance of tumour heterogeneity in RCC⁵. Intratumor heterogeneity can lead to underestimation of the tumour genomics landscape portrayed from single tumour-biopsy samples and may present major challenges to personalised medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumour adaptation and therapeutic failure through Darwinian selection. The study also revealed "branching evolutionary tumour growth, with 63 to 69% of all somatic mutations not detectable across every tumour region, emphasizing the complexity of treating RCC due to its genetic diversity⁵.

First-Line Systemic Therapies for RCC

The NCCN guidelines for metastatic renal cell carcinoma (RCC) recommend a multi-faceted approach, including cytoreductive nephrectomy for select patients and systemic therapy as primary treatment⁷. For clear cell histology, preferred first-line regimens include combinations such as axitinib with pembrolizumab, cabozantinib with nivolumab, and lenvatinib with pembrolizumab. Ipilimumab combined with nivolumab is also highly recommended. In cases where tumours are unresectable, systemic therapy options are prioritised. Best supportive care, including palliative radiation therapy and bisphosphonates or RANK ligand inhibitors for bony metastases, is essential for managing symptoms and improving quality of life⁷. (Table 1)

Table 1. First-line combination Phase III trial

	CheckMate 214 Nivo-lPl vs SUN n=550 vs n=546	KEYNOTE-426 Pembro-Axi vs SUN n=432 vs n=429	CM-9ER Nivo-Cabo vs SUN n=323 vs n=328	CLEAR Pembro-Lenva vs SUN n=355 vs n=357
Reference	Tannir NM et al8	Rini BI et al.9	Bourlon MT et al.10	Motzer RJ et al.11
Med flu, months	96	67	55	48
OS HR	0.72	0.84	0.77	0.79
mOS, months	52.7 vs 37.8	47.2 vs 40.8	46.5 vs 36.0	53.7 vs 54.3
Landmark OS	70% at 24 months	63% at 3 years	59% at 3 years	66% at 3 years
	35% at 90 months	42% at 5 years	49% at 4 years
PFS HR	0.88	0.69	0.58	0.47
mPFS, months	12.4 vs 12.3	15.7 vs 11.1	16.4 vs 8.4	23.9 vs 9.2
Landmark PFS	37% at 24 months 23% at 90 months	29% at 3 years 18% at 5 years	23% at 3 years	37% at 3 years
ORR, %	39 vs 32	61 vs 40	56 vs 28	71 vs 37
CR, %	12 vs 3	2 vs 4	13.6 vs 4.6	18 vs 4
Primary PD, %	18 vs 14	12 vs 17	6.5 vs 13.7	5 vs 14
Favourable, OS, HR	0.82	1.1	1.10	0.94
Favourable, PFS, HR	1.76	0.76	0.69	0.50
Sarcomatoid, OS, HR	0.46 (0.29-0.71)	0.58 (0.21-1.59)	0.36 (0.17-0.79)
Sarcomatoid, PFS, HR	0.50	0.54	0.42

CR, complete response, HR, hazard ratio; ORR, overall response rate; OS, overall survival; PD, partial disease; PFS, progression-free survival.

Residual disease in mRCC represents a critical challenge in the management of this malignancy, particularly following initial systemic therapies. Despite advancements in immunotherapy-based combinations that have significantly improved response rates, a considerable proportion of patients still exhibit residual disease post-treatment. This residual disease can be a source of ongoing morbidity and potential mortality, highlighting the necessity for additional therapeutic strategies aimed at achieving complete response¹².

Addressing residual disease is crucial for several reasons:

1. Prognostic Implications: The presence of residual disease often correlates with poorer overall survival and progression-free survival outcomes. Patients with residual disease after initial treatment typically have a higher risk of recurrence and metastasis, necessitating closer monitoring and more aggressive subsequent treatments.
2. Therapeutic Optimization: Understanding the biology and behaviour of residual disease can inform the development of more targeted and effective therapies. This may include the use of novel agents or combination therapies specifically designed to eradicate residual tumour cells that are resistant to initial treatment.
3. Quality of Life: Reducing or eliminating residual disease can significantly improve the quality of life for patients. Residual disease can lead to symptoms such as pain, organ dysfunction, and other complications, which can be mitigated through effective treatment strategies.
4. Research and Development: Studying residual disease provides valuable insights into the mechanisms of resistance to current therapies. This knowledge can drive the development of next-generation treatments and contribute to the overall advancement of cancer therapy.

In summary, the treatment of residual disease in mRCC is a critical component of patient management that has significant implications for survival, quality of life, and the development of future therapeutic approaches. Addressing this challenge requires ongoing research, innovative treatment strategies, and a comprehensive understanding of the underlying tumour biology​^12–14.

According to the study by Fabien Moinard-Butot et al. presented at ASCO GU 2023, treating residual disease in metastatic renal cell carcinoma (mRCC) significantly improves patient outcomes. Out of 80 patients initially treated with systemic therapy, 12 (15%) had progressive disease, 23 (29%) had stable disease, 36 (45%) had a partial response, and 9 (11%) achieved complete response. Following additional treatment for residual disease, the complete response rate increased to 24%, with 19 patients achieving complete response. This approach not only enhanced overall survival by converting partial and stable responses to complete responses but also improved quality of life by better management of symptoms. Local treatments included nephrectomy (n=4), nephrectomy with retroperitoneal lymph node dissection (n=2), lung resection with mediastinal lymph node dissection (n=1), lung resection (n=1), mediastinal lymph node dissection (n=1), liver microwave ablation (n=1), and retroperitoneal lymph node dissection (n=1). Viable renal cell carcinoma was confirmed in 7 out of 10 patients who underwent resection. Patients with systemic and local treatments had a median follow-up of 54.3 months, with significant improvements in progression-free survival and quality of life. The median time from the start of systemic treatment to the treatment of residual disease was 19.1 months (7.7-37.1 months). These findings highlight the critical role of addressing residual disease to optimise therapeutic outcomes in mRCC patients​¹².

Therapeutic Strategies for Residual RCC

Therapeutic strategies for residual renal cell carcinoma (RCC) include a combination of surgical interventions, local ablative therapies, systemic treatments, and emerging approaches. Surgical options such as nephrectomy, lung resection, and lymph node dissection are employed to remove the primary tumour and metastatic sites, reducing the tumour burden. Local ablative therapies like radiofrequency ablation, cryoablation, and stereotactic body radiation therapy (SBRT) target specific areas of residual disease to destroy cancer cells. A multidisciplinary approach, involving regular tumor board discussions and continuous monitoring, ensures individualised and adaptive treatment plans, ultimately improving patient outcomes and quality of life​.

In an earlier study conducted by Alt et al., metastasectomy significantly improved survival outcomes for patients with mRCC¹⁵. The study showed that complete surgical resection of metastases increased the median cancer-specific survival (CSS) to 4.8 years, compared to 1.3 years for those without complete resection. The 5-year CSS rate was notably higher at 49.4% for patients who had complete metastasectomy, versus 13.9% for those who did not. Despite these encouraging results, it is important to note that very few patients in the study received the treatment options available today¹⁵.

In the study by Lyon et al., the efficacy of complete metastasectomy for mRCC was examined in the context of more recently approved systemic therapies. This research included 586 patients who underwent nephrectomy between 2006 and 2017, with 158 (27%) of these patients receiving complete metastasectomy. Notably, 93% of the patients who underwent complete metastasectomy did not receive systemic therapy for the index metastasis. The results demonstrated a significant survival benefit: the two-year cancer-specific survival (CSS) rate was 84% (132 out of 158 patients) in those who underwent complete metastasectomy, compared to 54% (231 out of 428 patients) in those who did not (p < 0.001). In addition, complete metastasectomy was associated with a significantly reduced risk of death from RCC (HR 0.47, 95% CI 0.34-0.65, p < 0.001), even after adjusting for age, gender, timing, number, and location of metastases. Of the 158 patients treated with complete metastasectomy, 72% developed subsequent metastasis, with a median metastasis-free survival of 1.4 years.

These findings suggest that complete surgical resection of metastases continues to offer substantial benefits in the post-cytokine era and should be considered for suitable patients through a process of shared decision-making¹⁶.

According to the study by Yip et al., nephrectomy following immune checkpoint inhibitor (ICI) therapy is both safe and effective for patients with metastatic renal cell carcinoma (RCC). The study found that nephrectomy post-ICI therapy did not significantly increase perioperative complications or readmission rates compared to similar surgeries without prior ICI treatment. The 90-day complication rate was 24%, with a median hospital stay of 3 days. Furthermore, the study reported a complete pathologic response in 5% of patients and highlighted an estimated 3-year overall survival rate of 82%, demonstrating the feasibility and potential benefit of nephrectomy as a consolidative therapy in select patients​¹⁷.

Compared with the study by Yip et al., which assessed nephrectomy following ICI therapy and reported manageable perioperative risks and a lower complication rate, the research by Pignot et al. reveals a higher postoperative complication rate of 55%, including major complications and one surgery-related death. This difference is attributed to the significant surgical complexities caused by inflammatory infiltration due to prolonged ICI exposure, which made finding dissection planes challenging in 82% of cases. Despite these challenges, Pignot et al. demonstrated promising efficacy, with 73% of patients free from progression and 54% free from systemic treatment one year after surgery. These findings suggest that, while nephrectomy following ICIs presents substantial surgical challenges, it can still be an effective strategy to achieve long-term remission in selected mRCC patients¹⁸.

In a retrospective cohort study of 522 patients undergoing 740 metastasectomies for mRCC at two high-volume centres between 2005 and 2020, it was found that fewer than 10% experienced major complications (Clavien-Dindo III-V) within 30 days of surgery. Significant factors associated with postoperative complications included age, body mass index, ASA score, concurrent nephrectomy, multiple metastatic sites, pancreatic resection, and metastasis size. Despite these risks, the study concluded that favourable perioperative outcomes are achievable in well-selected patients at specialised centres¹⁹.

In a study by Ferriero et al., a 10-year single-centre experience was analyzed to assess the impact of metastasectomy on survival outcomes in patients with RCC. This prospective study included patients treated with either partial or radical nephrectomy who developed oligometastatic disease during follow-up. Results showed that patients who underwent metastasectomy had significantly improved OS compared to those who received systemic treatment only. The 2-year, 5-year, and 10-year OS probabilities were notably higher in the metastasectomy group, with rates of 93.8%, 82.8%, and 79.5%, respectively²⁰.

The benefit of surgical metastasectomy (SM) for patients with mRCC remains uncertain due to a lack of high-level evidence on its survival benefits in the context of systemic therapy. A meta-analysis of 56 retrospective studies suggests that SM may benefit selected mRCC patients, particularly those with oligometastatic disease and favourable risk profiles, with median OS ranging from 36 to 142 months compared to 8 to 27 months for non-SM patients. Currently, there is limited data on the role of SM after TKI therapy and no data on its role following immune checkpoint inhibitor ICI exposure. Despite the lack of randomised clinical data, existing studies support SM as a viable option for prolonging survival and avoiding systemic therapy in selected patients with limited metastases and good health status​¹⁴.

Schoenhals et al. demonstrate the efficacy of SBRT in managing oligoprogressive mRCC. By targeting limited sites of progression without altering systemic therapy, SBRT extended the median modified mPFS to 9.2 months. Patients receiving SBRT while on immunotherapy showed a significantly longer median mPFS (>28.4 months). The treatment was well-tolerated, with most toxicities being grade 1 or 2²¹.

Two recent studies have highlighted the evolving role of radiotherapy in treating mRCC. The study by Tang et al. demonstrates the feasibility and efficacy of SBRT in lieu of systemic therapy for oligometastatic RCC. This approach achieved a high local control rate of 97% and a 1-year progression-free survival rate of 64%, with minimal severe adverse effects. The study challenges the traditional view of RCC as radioresistant, showing that modern SBRT techniques can effectively manage oligometastatic RCC, offering a less toxic alternative to systemic therapies​²² Likewise, Ali et al.'s review on the role of SBRT in RCC provides comprehensive evidence that contemporary radiotherapy techniques yield high local control rates exceeding 90% and maintain low rates of grade 3-4 toxicities. This indicates that RCC is no longer considered radioresistant with advanced radiotherapy modalities²³. Both studies underscore the potential of SBRT to extend survival and improve quality of life in mRCC patients by providing effective local control with minimal toxicity, thereby deferring or reducing the need for systemic therapy​^22,23.

In a recent study by Chalkidou et al., a prospective, registry-based, single-arm, observational evaluation was conducted across 17 NHS radiotherapy centres in England to assess the efficacy of SBRT in patients with extracranial oligometastatic solid cancers. The study included 1422 patients and demonstrated high overall survival rates of 92.3% at 1 year and 79.2% at 2 years²⁴.

In a recent meta-analysis by Zaorsky et al., SBRT demonstrated significant efficacy and safety in treating oligometastatic RCC. The study, which included 28 studies with 1602 patients and 3892 lesions, found a 1-year local control rate of approximately 90% for both extracranial and intracranial metastases. The 1-year survival rates were 86.8% for extracranial and 49.7% for intracranial disease. Importantly, the incidence of grade 3-4 toxicity was very low, at 0.7% for extracranial and 1.1% for intracranial disease. These findings suggest that SABR is a safe and effective treatment option for RCC metastases²⁵.

Local treatment of metastases, such as metastasectomy or radiotherapy, remains controversial in mRCC. A systematic review of comparative studies found that patients undergoing complete metastasectomy had better survival and symptom control, including pain relief in bone metastases, compared to those receiving incomplete or no metastasectomy. However, the evidence was limited by high risks of bias and confounding²⁶.

In conclusion, multidisciplinary management of residual RCC following first-line systemic therapy is crucial for optimizing patient outcomes. A combination of cytoreductive nephrectomy, metastasectomy, and SBRT has shown promising results in managing mRCC. These strategies aim to reduce tumour burden, delay systemic therapy, and improve quality of life. A personalised approach is essential, where treatment decisions are tailored based on the patient's disease progression, risk factors, and overall health status. By integrating surgical and local ablative techniques with systemic therapies, clinicians can effectively manage residual disease, potentially achieving long-term disease control and enhancing patient survival.

Future Directions

1. Research on Mechanisms of Resistance: Further studies are needed to understand the biological mechanisms underlying resistance in residual RCC to develop targeted therapies.
2. Innovative Therapeutic Approaches: Investigate new drug combinations and novel agents that can effectively target resistant tumour cell populations in residual disease.
3. Personalised Medicine: Enhance personalised treatment plans by utilizing advanced genomic profiling to tailor therapies based on individual tumour characteristics and heterogeneity.
4. Integration of Multidisciplinary Care: Promote a multidisciplinary approach, combining surgical, local ablative, and systemic treatments to optimise patient outcomes.
5. Clinical Trials: Conduct more clinical trials focused on the efficacy of combining systemic therapies with local treatments like SBRT and metastasectomy for managing residual RCC.

CONFLICT OF INTEREST

Advisory boards: Yüksel Ürün has served on advisory boards for Abdi-İbrahim, Astellas, AstraZeneca, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen ilaç, Gilead, GSK, Janssen, Merck, MSD, Novartis, Pfizer, Roche. Travel, honoraria or consultation fees: Yüksel Ürün received honoraria or has served as a consultant for Abdi-İbrahim, Astellas, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen İlaç, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Roche

FUNDING

No funding was received for this work.

REFERENCES

1. Bukavina L, Bensalah K, Bray F, et al. Epidemiology of Renal Cell Carcinoma: 2022 Update. Eur Urol. 2022;82(5):529-542. 10.1016/j.eururo.2022.08.019
2. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. 10.3322/caac.21834
3. Signoretti S, Flaifel A, Chen YB, Reuter VE. Renal Cell Carcinoma in the Era of Precision Medicine: From Molecular Pathology to Tissue-Based Biomarkers. Journal of Clinical Oncology. 2018;36(36):JCO.2018.79.225. 10.1200/JCO.2018.79.2259
4. Chen YW, Wang L, Panian J, et al. Treatment Landscape of Renal Cell Carcinoma. Curr Treat Options Oncol. 2023;24(12):1889-1916. 10.1007/S11864-023-01161-5
5. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883-892. 10.1056/NEJMOA1113205
6. Turajlic S, Swanton C, Boshoff C. Kidney cancer: The next decade. J Exp Med. 2018;215(10):2477. 10.1084/JEM.20181617
7. National Comprehensive Cancer Network. Published July 11, 2024. Accessed July 10, 2024. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf
8. Tannir NM, Escudier B, McDermott DF, et al. Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial. J Clin Oncol. 2024;42(4_suppl):363-363. 10.1200/JCO.2024.42.4_SUPPL.363
9. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: 5-year analysis of KEYNOTE-426. J Clin Oncol. 2023;41(17_suppl):LBA4501-LBA4501. 10.1200/JCO.2023.41.17_SUPPL.LBA4501
10. Bourlon MT, Escudier B, Burotto M, et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Results from 55-month follow-up of the CheckMate 9ER trial. J Clin Oncol 2024;42(4_suppl):362-362. 10.1200/JCO.2024.42.4_SUPPL.362
11. Motzer RJ, Porta C, Eto M, et al. Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study. Journal of Clinical Oncology. 2024;42(11):1222-1228. 10.1200/JCO.23.01569/SUPPL_FILE/PROTOCOL_JCO.23.01569.PDF
12. Moinard-Butot F, Oriel M, Tricard T, et al. Effect of treatment of residual disease after immunotherapy-based combinations on complete response rate in metastatic renal cell carcinoma. J Clin Oncol. 2023;41(6_suppl):601-601. 10.1200/JCO.2023.41.6_SUPPL.601
13. Dason S, Lacuna K, Hannan R, Singer EA, Runcie K. State of the Art: Multidisciplinary Management of Oligometastatic Renal Cell Carcinoma. Am Soc Clin Oncol Educ Book 2023;(43). 10.1200/EDBK_390038
14. Ouzaid I, Capitanio U, Staehler M, et al. Surgical Metastasectomy in Renal Cell Carcinoma: A Systematic Review. Eur Urol Oncol. 2019;2(2):141-149. 10.1016/j.euo.2018.08.028
15. Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML. Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer. 2011;117(13):2873-2882. 10.1002/CNCR.25836
16. Lyon TD, Thompson RH, Shah PH, et al. Complete Surgical Metastasectomy of Renal Cell Carcinoma in the Post-Cytokine Era. J Urol. 2020;203(2):275-281. 10.1097/JU.0000000000000488
17. Yip W, Ghoreifi A, Gerald T, et al. Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study. Eur Urol Oncol. 2023;6(6):604-610. 10.1016/J.EUO.2023.03.003
18. Pignot G, Thiery-Vuillemin A, Walz J, et al. Nephrectomy After Complete Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma: A New Surgical Challenge? Eur Urol. 2020;77(6):761-763. 10.1016/J.EURURO.2019.12.018
19. Lyon TD, Roussel E, Sharma V, et al. International Multi-institutional Characterization of the Perioperative Morbidity of Metastasectomy for Renal Cell Carcinoma. Eur Urol Oncol. 2023;6(1):76-83. 10.1016/J.EUO.2022.11.003
20. Ferriero M, Cacciatore L, Ochoa M, et al. The Impact of Metastasectomy on Survival Outcomes of Renal Cell Carcinoma: A 10-Year Single Center Experience. Cancers (Basel). 2023;15(13):3332. 10.3390/CANCERS15133332
21. Schoenhals JE, Mohamad O, Christie A, et al. Stereotactic Ablative Radiation Therapy for Oligoprogressive Renal Cell Carcinoma. Adv Radiat Oncol. 2021;6(5). 10.1016/J.ADRO.2021.100692
22. Tang C, Msaouel P, Hara K, et al. Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial. Lancet Oncol. 2021;22(12):1732-1739. 10.1016/S1470-2045(21)00528-3
23. Ali M, Mooi J, Lawrentschuk N, et al. The Role of Stereotactic Ablative Body Radiotherapy in Renal Cell Carcinoma. Eur Urol. 2022;82(6):613-622. 10.1016/J.EURURO.2022.06.017
24. Chalkidou A, Macmillan T, Grzeda MT, et al. Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study. Lancet Oncol. 2021;22(1):98-106. 10.1016/S1470-2045(20)30537-4
25. Zaorsky NG, Lehrer EJ, Kothari G, Louie A V., Siva S. Stereotactic ablative radiation therapy for oligometastatic renal cell carcinoma (SABR ORCA): a meta-analysis of 28 studies. Eur Urol Oncol. 2019;2(5):515-523. 10.1016/J.EUO.2019.05.007
26. Dabestani S, Marconi L, Hofmann F, et al. Local treatments for metastases of renal cell carcinoma: a systematic review. Lancet Oncol. 2014;15(12):e549-e561. 10.1016/S1470-2045(14)70235-9

 

©2024 the author(s). Published with license by Medicom Medical Publishers.
This an Open Access article distributed under the terms of the Creative Commons attribution-non Commercial license (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Posted on 17 October 202417 October 2024