Podium 01
無法切除之未分化肉瘤於重粒子放射治療（CIRT）後達到病理完全緩解
–案例報告
林子翔1、魏子鈞1,2,3
1台北榮民總醫院 泌尿部；2陽明大學醫學院泌尿學科；3書田泌尿學研究中心
Pathologic Complete Response After Carbon Ion Radiation Therapy (CIRT) in Unresectable, Undifferentiated Low- to Intermediate-Grade Sarcoma : A Case Report
Tzu-Hsiang Lin 1, Tzu-Chun Wei 1,2,3
1Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan
2Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
3Shu-Tien Urological Institute, National Yang-Ming University, Taipei, Taiwan
Introduction
Undifferentiated sarcomas are mesenchymal tumors that most commonly arise in the skin and soft tissues and are typically managed with surgical resection. We report a rare case of unresectable disease with genitourinary tract involvement that achieved a pathologic complete response following treatment with carbon ion radiotherapy (CIRT).
Case Presentation
A 25-year-old woman initially presented with dysuria. Ultrasound revealed a suspicious bladder lesion, and subsequent CT imaging demonstrated a fungating tumor at the bladder neck. She underwent transurethral resection of bladder tumor (TURBT), with pathology showing an undifferentiated low- to intermediate-grade spindle- to round-cell sarcoma. Molecular analysis identified a single nucleotide polymorphism in PDGFRA exon 10, with no fusion variants or other alterations detected on Archer fusion testing.
She was referred to our medical center for further management. A follow-up CT scan 3 months after TURBT demonstrated a 2.8 cm filling defect at the right posterior bladder neck, highly suspicious for residual or recurrent disease. She was deemed unsuitable for surgical resection, and after careful shared decision making, carbon ion radiotherapy (CIRT) was selected. CIRT was delivered in 16 fractions to a clinical target volume (CTV) of 70.4 Gy. Post-treatment MRI showed changes in the urethra consistent with treatment effect, without evidence of recurrence.
Functionally, she was able to void smoothly without straining immediately after treatment. Uroflowmetry performed 6 months after CIRT demonstrated a maximum flow rate of 14 mL/min and a mean flow rate of 8 mL/min at a voided volume of 145 mL.
Dysuria was noted during the first 3 months following CIRT but gradually improved. In contrast, intermittent painful hematuria worsened approximately 1 year after treatment, prompting transurethral coagulation for bleeding control and repeat TURBT. A bulging lesion at the anterior urethra, located within the CIRT treatment field, was biopsied. Pathology revealed microcalcifications and chronic inflammation, with no evidence of malignancy. No additional lesions were identified in the urethra or bladder.
Since the procedure, she has had no further episodes of hematuria. She remains in sustained complete remission of urethral sarcoma 1.5 years after CIRT.
Discussions
Undifferentiated sarcomas, previously termed malignant fibrous histiocytomas, comprise a heterogeneous group of malignant mesenchymal tumors and are rare, with an estimated prevalence of 0.08–1 per 100,000. These tumors are typically aggressive and are broadly classified into four major histologic subtypes: pleomorphic, epithelioid, spindle cell, and round cell. According to a SEER-based epidemiologic study, the most commonly involved sites are the skin and soft tissues, whereas involvement of the genitourinary (GU) tract is exceedingly uncommon¹.
Surgical resection remains the cornerstone of treatment for patients with soft tissue sarcoma (STS), while the roles of radiotherapy and systemic therapy are determined by tumor stage, resectability, and grade². In selected cases, tumors with specific genetic alterations may benefit from tailored therapies³. However, no clinically actionable genetic alterations were identified in this patient.
Radiation therapy alone can provide reasonable long-term local control in patients with unresectable STS⁴. The efficacy of carbon ion radiotherapy (CIRT) in this setting has been demonstrated for over two decades. A phase I/II dose-escalation study reported a 3-year local control rate of 73% and a 1-year local control rate of 88% in 57 patients treated with 52.8–73.6 Gy (RBE) in 16 fractions⁵. More recently, a study of 76 patients with unresectable retroperitoneal sarcoma treated with CIRT (70.4 Gy RBE in 16 fractions) demonstrated a 5-year local control rate of 72% and a 5-year overall survival rate of 49.4%, with a low incidence (5.2%) of grade ≥3 late toxicities⁶. In our case, serial MRI follow-up at 3- to 6-month intervals after CIRT has shown no evidence of recurrence. Additionally, biopsy samples from the anterior urethra and bladder neck revealed only inflammatory changes.
The tumor’s location at the junction of the bladder neck and anterior urethra also influenced the decision to pursue CIRT. Pelvic organs such as the bladder, urethra, and rectum are particularly sensitive to radiation, with potential toxicities including radiation cystitis, fistula formation, strictures, secondary malignancies, radiation proctitis, and rectal fistulae⁷. Despite these concerns, CIRT has demonstrated favorable toxicity profiles in prostate cancer, with most genitourinary adverse events limited to grade 1–2⁸˒⁹. In contrast, our patient experienced grade 3 late GU toxicity requiring endoscopic coagulation, likely reflecting the tumor’s proximity to GU mucosa. Encouragingly, hematuria resolved completely following the procedure. Moreover, preservation of both voiding and storage function after CIRT has contributed positively to her quality of life.
Conclusion
Undifferentiated sarcomas arising at the bladder neck are exceedingly rare. Optimal management is critical, as these tumors carry a high risk of recurrence, and adjacent pelvic organs are particularly susceptible to treatment-related injury that may significantly impact quality of life. Our case demonstrates that carbon ion radiotherapy (CIRT), delivered at 70.4 Gy (RBE) in 16 fractions, may offer an effective and safe treatment option for patients with unresectable undifferentiated sarcomas.
References