Renal squamous cell carcinoma postoperative recurrence treated with sunitinib combined with radiotherapy: a case report

Introduction

Primary renal squamous cell carcinoma (SCC) is a rare malignancy of the kidney, accounting for less than 1% of all renal malignant tumors (1). It is often associated with chronic irritation caused by renal calculi, infection, or hydronephrosis (2). Due to its aggressive nature and lack of early specific symptoms, patients are usually diagnosed at an advanced stage, resulting in a poor prognosis, with a 5-year survival rate below 20% (3). For localized disease, surgery remains the mainstay of treatment; however, postoperative recurrence rates are high, and the role of adjuvant therapy remains unclear (4). Renal cell carcinoma (RCC) has traditionally been considered radioresistant, and radiotherapy (RT) has only been used for palliative treatment of metastatic lesions (5). However, modern technologies such as TomoTherapy, a device that integrates intensity-modulated RT and image-guided RT, allow for precise dose delivery and have broadened the application of RT in renal tumors, potentially improving local control. Sunitinib, a tyrosine kinase inhibitor (TKI), is standard treatment for metastatic clear cell RCC, but its efficacy in non-clear cell histologies, including SCC, is uncertain (6). This report presents a case of locally advanced renal SCC that developed postoperative local recurrence and was successfully treated with sunitinib combined with TomoTherapy. We present this article in accordance with the CARE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0458/rc).

Case presentation

A 56-year-old male presented to the Emergency Department of Zhongnan Hospital of Wuhan University in November 2020 with a 2-week history of worsening right flank pain. Since November 2020, the patient had experienced intermittent right flank pain without apparent cause. His past medical history was unremarkable except for occasional renal colic. Contrast-enhanced computed tomography (CT) of the abdomen revealed an enlarged right kidney with multiple ill-defined hypodense lesions, the largest measuring approximately 8 cm × 6 cm, accompanied by perirenal fascial thickening and infiltration of the right psoas muscle (Figure 1A). Dense calcifications were observed in the renal pelvis and proximal ureter, suggesting staghorn calculi. The left kidney showed compensatory enlargement, and a stone measuring approximately 7 mm in diameter was noted at the left ureterovesical junction. Laboratory tests revealed leukocytosis (white blood cell count 15.12×10⁹/L). Renal function and serum calcium levels were normal. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 Preoperative imaging and histopathological findings of the renal tumor. (A) Preoperative CT showing a large mass in the right kidney with invasion of the psoas muscle. (B) Histopathology of the resected tumor: hematoxylin and eosin staining showing keratinizing squamous cell carcinoma (upper panel: ×40; lower panel: ×200). CT, computed tomography.

On January 5, 2021, the patient underwent right radical nephrectomy, partial psoas muscle resection, and ipsilateral ureteroscopic laser lithotripsy under general anesthesia. Postoperative pathological examination revealed keratinizing SCC (8 cm × 7.5 cm × 7 cm), with tumor invasion into perirenal and renal sinus fat, lymphovascular invasion, and no perineural invasion (Figure 1B). Surgical margins were negative, and no metastasis was found in the four retroperitoneal lymph nodes submitted. According to the American Joint Committee on Cancer (AJCC) 8th edition staging system, the tumor was classified as pT4N0Mx. Immunohistochemical staining for programmed death-ligand 1 (PD-L1) was performed using the 22C3 pharmDx assay, revealing a combined positive score (CPS) of 8. Postoperatively, the patient experienced delayed wound healing, which resolved with conservative treatment.

One month after surgery (February 2021), follow-up outpatient abdominal CT revealed new soft tissue density in the right renal fossa, suggestive of local tumor recurrence (Figure 2A). The patient was promptly referred to the Department of Radiation Oncology. Given that the recurrent lesion was confined to the renal bed and adjacent psoas muscle without evidence of distant metastasis, the multidisciplinary team recommended a combined treatment approach with sunitinib and RT.

Figure 2 Imaging assessment before, during, and after combination therapy. (A) CT scan 1 month postoperatively showing a mass in the right psoas muscle. (B) Delineation of radiation target volume. (C) Dose-volume histogram. (D) CT scan after sunitinib combined with radiotherapy showing significant regression of soft tissue opacity in the renal fossa. CT, computed tomography.

The treatment selection was guided by the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version 3.2021), which list clinical trial or sunitinib as “Preferred Regimens” for non-clear cell renal cell carcinoma (nccRCC). Cabozantinib is listed as an “Other Recommended Regimen” for this histology. Although cabozantinib was listed as a treatment option, it was not readily available at our institution at the time, and the patient’s financial constraints precluded its use. Sunitinib, being a preferred regimen that was more accessible and included in the national health insurance formulary, was therefore the feasible targeted agent. Postoperative PD-L1 immunohistochemistry (22C3 pharmDx assay) revealed a CPS of approximately 8, indicating PD-L1 positivity; however, at the time of treatment initiation, evidence for immunotherapy in renal SCC was extremely limited, and this result was therefore considered as reference for potential future immunotherapy rather than as an indication for first-line programmed cell death protein-1 (PD-1)/PD-L1 blockade. Systemic chemotherapy was deferred due to concerns about immunosuppression given the patient’s delayed wound healing. Surveillance alone was deemed inappropriate given the aggressive early recurrence. The multidisciplinary team therefore opted for sunitinib combined with RT to achieve both systemic control and enhanced local control of the recurrent lesion.

Sunitinib was administered at a dose of 50 mg daily on a 4-week-on/2-week-off schedule and was continued after RT completion. Concurrently, the patient underwent TomoTherapy to the recurrent lesion. The planned target volume received a total dose of 50 Gy in 25 fractions, with a single fraction dose of 200 cGy, administered five times per week, with strict adherence to organ-at-risk dose constraints (Figure 2B,2C). Treatment was well tolerated, with only mild fatigue and transient nausea.

The last response evaluation in July 2021 (after completion of two cycles of sunitinib and RT) revealed a significant reduction in soft tissue density in the right renal fossa on CT, which was assessed as a partial response according to RECIST criteria (Figure 2D). The patient’s Karnofsky Performance Status score improved from 60 to 90, body weight increased by 8 kg, and anemia resolved. No distant metastasis was observed. No further imaging follow-up was available thereafter due to patient-related factors.

Discussion

Primary renal SCC is a rare and aggressive malignancy, typically diagnosed at an advanced stage. As seen in this patient, chronic inflammation due to renal calculi is a known risk factor (2). Complete surgical resection offers the only chance for cure; however, local recurrence and distant metastasis are common (3). No established adjuvant therapy exists, and available data are limited to case reports and small case series.

Previous reports have described various systemic treatment approaches for renal SCC. A 2021 case report documented complete pathological remission after neoadjuvant chemotherapy with albumin-bound paclitaxel combined with nedaplatin in a patient with locally advanced renal SCC (7). More recently, a 2025 case report described a patient with advanced-stage renal SCC and pulmonary metastases who achieved disease remission following combined chemoradiotherapy and immunotherapy (8). Additionally, cases of metastatic RCC treated with hypofractionated RT concurrent with sunitinib have demonstrated near-complete responses (9). However, to our knowledge, this is the first report specifically documenting the efficacy of sunitinib combined with conventional fractionated RT for postoperative local recurrence of renal SCC, a distinct clinical scenario that has not been previously described.

The role of RT in RCC has evolved. While RCC is historically considered radioresistant, the combination with targeted agents offers a new perspective to overcome this challenge. In the present case, we utilized TomoTherapy to deliver conventional fractionated RT (50 Gy in 25 fractions), which achieved favorable local control when combined with sunitinib.

The synergistic effect between sunitinib and conventional fractionated RT is likely driven by several mechanisms. First, sunitinib, a multitargeted TKI, can normalize tumor vasculature and improve tumor oxygenation (10,11). This alleviation of hypoxia can enhance the cytotoxicity of radiation by promoting the formation of irreversible DNA double-strand breaks. Second, TKIs like sunitinib can inhibit the repair of radiation-induced DNA damage, thereby increasing the radiosensitivity of tumor cells (12). In our patient, this combined approach resulted in a significant response in the recurrent lesion, supporting the potential for clinical synergy.

Sunitinib’s efficacy in non-clear cell subtypes is variable (6). Some reports suggest that renal nccRCC may harbor mutations in genes such as TP53 and CDKN2A, and responses to TKIs are generally poor (13). However, the combination with RT may offer a strategy to overcome such resistance.

Furthermore, the patient’s PD-L1 CPS of 8 indicates that immunotherapy may be beneficial. Recent clinical trials have demonstrated the activity of immune checkpoint inhibitors in nccRCC (14). RT is known to induce immunogenic cell death and enhance anti-tumor immunity, potentially synergizing with PD-1/PD-L1 blockade (15). This raises the possibility of a “MAX” approach combining immunotherapy, targeted therapy, and RT in the future.

A limitation of this report is the lack of long-term imaging follow-up beyond July 2021, as scheduled follow-up was interrupted for patient-related reasons.

Conclusions

In conclusion, we report a case of locally advanced renal SCC that achieved durable local control with sunitinib and conventional fractionated RT delivered via TomoTherapy following surgery. This multimodal treatment strategy may offer a promising approach for this rare and aggressive tumor, though further studies are warranted to validate this approach and to explore the optimal combination and sequencing of therapies, including the potential incorporation of immunotherapy.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0458/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0458/prf

Funding: This work was supported by the National Natural Science Foundation of China (No. 81902597), Zhejiang Province Medical and Health Scientific Research Project (No. 2023KY677), and Wu Jieping Medical Foundation (No. 320.6750.2020-10-88).

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0458/coif). Both authors report that this work was supported by the National Natural Science Foundation of China (No. 81902597), Zhejiang Province Medical and Health Scientific Research Project (No. 2023KY677), and Wu Jieping Medical Foundation (No. 320.6750.2020-10-88). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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