Case - Radiation-induced sarcoma: A pitfall during PSMA-targeted radioligand therapy

subsequently referred to our centre for [ 177 Lu]Lu-PSMA-617 therapy.Although he demonstrated a favourable initial response, he later developed an undifferentiated sarcoma, as detailed below. CASE REPORTA 68-year-old male with a long-standing history of prostate cancer presented with castrationresistant disease and bone-only metastatic involvement.He was initially diagnosed with localized prostate adenocarcinoma, International Society of Urological Pathology (ISUP) Grade Group 5, eight years prior to referral, and underwent radical prostatectomy demonstrating pT2c disease.Two years postoperatively, he developed biochemical recurrence accompanied by pelvic lymphadenopathy on CT.He subsequently underwent retroperitoneal pelvic lymph node dissection followed by salvage external-beam radiotherapy in September 2013 (6600 cGy to the prostate bed and 5400 cGy to pelvic nodes) and was commenced on androgen deprivation therapy (ADT).His pelvic radiotherapy course was complicated by radiation-induced proctitis and cystitis.Approximately one year later, his PSA progressively increased to 9.2 ng/mL, and bone scintigraphy revealed metastatic lesions in the left iliac bone and left ischium.He received palliative radiation with a single fraction of 800 cGy to the left hip and ischium in January 2015.Systemic therapy with abiraterone acetate, prednisone, and denosumab was initiated; however, after approximately 16 months, he demonstrated biochemical progression and was switched to enzalutamide.Due to worsening left pelvic pain, pelvic re-irradiation was delivered using IMRT to minimize bladder and rectal dose exposure (2200 cGy in 5 fractions) in June 2016.His response to enzalutamide was short-lived, and he commenced alpha-emitting radiopharmaceutical therapy with [ 223 Ra]Radium dichloride in February 2017, completing the standard 6-dose treatment by August 2017.In addition, he received 10 cycles of docetaxel by mid-2018.Subsequently, the patient was enrolled in a clinical trial and received [ 177 Lu]Lu-PSMA-617 at a dose of 7.4 GBq per cycle every six weeks, for a total of six cycles, completed in April 2020.He demonstrated both biochemical and radiographic response to therapy.His baseline prostatespecific antigen (PSA) decreased from 109 ng/mL to 2.1 ng/mL following completion of radioligand treatment.Post-therapy PSMA PET/CT revealed marked reduction in the extent and intensity of radiotracer uptake throughout the skeleton (Figure 1).However, a solitary focusIn the left iliac bone demonstrated persistent uptake (Figure 1).Targeted evaluation with contrast-enhanced CT and MRI identified a destructive osseous lesion with an enhancing soft tissue component, which continued to enlarge despite stability of the remainder of his disease burden (Figure 2).Three months following his final [ 177 Lu]Lu-PSMA-617 treatment-at which time his PSA remained stable-a biopsy of the lesion was performed.Histopathological and immunohistochemical analysis confirmed an undifferentiated sarcoma.Review of his treatment history revealed that he had previously received external-beam radiotherapy to the pelvis in 2013, 2015, and 2016.The site of sarcoma development was located CUAJ -Residents' Room Akbari-Kelachayeh et al Case -Radiation-induced sarcoma