ASCO GU 2025: Management of Biochemical Recurrence after Radiation Therapy for Localized Prostate Cancer: Reirradiation, Brachytherapy and SBRT.

(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA was host to the Case-Based Session: Management of Biochemical Recurrence After Radiation Therapy for Localized Prostate Cancer. Dr. Juanita Crook discussed the Radiation Oncologist Perspective on the Management of Biochemical Recurrence After Radiation Therapy for Localized Prostate Cancer.

Dr. Crook began her presentation by saying that she was going to cover the different approaches to salvage radiorecurrent prostate cancer. She highlighted the advantages of brachytherapy, including its conformality and more rapid dose fall-off. She then compared whole gland versus focal approaches, as well as the difference between low dose rate (permanent seed implant) and high dose rate (temporary implant) brachytherapy. Additionally, she covered external beam radiation, differentiating between conventional fractionation and ultra-hypofractionation (stereotactic body radiotherapy, or SBRT).

Dr. Crook recapitulated the case presented by Dr. Cookson at the beginning of the session. The case involved a 62-year-old patient with a previous Gleason grade 2, T1c prostate cancer, who had undergone radiotherapy 5 years ago. His nadir PSA was 0.5 ng/ml, and his current PSA was 5.9 ng/ml. For his primary treatment, the patient had received intensity-modulated radiation therapy (IMRT) with a dose of 79.2 Gy, delivered at 1.8 Gy per fraction, targeting the prostate and half of the seminal vesicles. At the time of biochemical recurrence, multi-parametric MRI showed a prostate lesion at the left peripheral zone (PIRADS 5) and a biopsy confirmed radiorecurrent disease on the left peripheral zone. A PSMA-PET scan corroborated the findings with no evidence of distant metastasis. Dr. Crook note that there are three treatment options she could offer this patient for treating his recurrence.

Dr. Crook discussed the RTOG 0526 multicenter prospective trial, which included 92 patients. The study enrolled patients with Gleason grade 1 or 2 prostate cancer, prostate volume less than 45 cc, and a PSA level of less than 10 ng/ml. Patients had no persistent radiation toxicity greater than grade 2 according to the CTCAE V3. The median prior radiation dose was 74 Gy, and the trial was conducted before the availability of multi-parametric MRI or PSMA PET imaging. The study found that 14% of patients experienced late grade 3 genitourinary or gastrointestinal adverse events. Moreover, the 5-year freedom from biochemical failure was 68%, and the 10-year rate was 54%. While local failures were rare, occurring in only 5% of patients at 10 years.¹

In a similar trial, Dr. Meraouna and colleagues evaluated 94 patients with radiorecurrent prostate cancer who had been initially treated with either external beam radiation therapy (78%) or low-dose-rate brachytherapy. These patients were then treated with salvage low-dose-rate brachytherapy (LDR) between 2006 and 2021. The target volume in the study varied, with options including the whole gland, a boost to the gross tumor volume (GTV), the hemigland, or only the GTV. The prescribed dose ranged from 90 to 145 Gy.²

Each target volume carries its own risks. For example, whole-gland treatment with a dose of greater than 140 Gy has historically been associated with up to 14% grade 3 toxicity. Whole-gland treatment with a boost to the lesion is probably associated with less toxicity and is safer than hemigland or ultrafocal approaches, particularly when the disease is diffuse or initially present elsewhere. The hemigland approach, with or without a boost, would be Dr. Crook’s preferred choice for the patient discussed earlier. Lastly, the ultrafocal approach carries a risk of further intraprostatic failure, especially when performed with seeds.

In Meraouna et al.'s study, the failure-free survival rate was 66% at 3 years of follow-up. Regarding treatment-related morbidities, 12.3% of patients experienced grade 3 genitourinary (GU) toxicity, and 1.2% experienced grade 3 gastrointestinal (GI) toxicity.²

The second treatment option for this case could be high-dose-rate (HDR) brachytherapy, with several potential strategies. One approach involves whole-gland HDR, while another approach combines whole-gland treatment at a lower dose (10 Gy x 2) with a higher dose to the dominant intraprostatic lesion (DIL) (13.5 Gy x 2), or DIL alone with a sufficient margin. Challenges related to treatment planning include contouring and registration errors, with a recommended isotropic margin of 0.5 cm cropped at the organs at risk (OARs), as suggested by Mason et al.³

Moreover, In the context of prior external beam radiotherapy (EBRT), the treatment strategy would be whole-gland HDR with a focal boost, while prior brachytherapy cases would warrant a focal approach.

Regarding toxicity, acute toxicity for HDR, it has been reported to show no grade 2 gastrointestinal and no grade 3 genitourinary complications.⁴ However, late toxicity can vary based on the treatment approach. Grade 3 genitourinary toxicity ranges between 10% and 23.5% and in some series cases of fistula have been reported. 

A study comparing HDR and low-dose-rate (LDR) brachytherapy in 61 and 37 patients, respectively, with radio-recurrent prostate cancer showed no significant differences in 3-year PSA recurrence-free survival (RFS) between the two modalities. Additionally, there were no statistically significant differences in toxicity between HDR and LDR brachytherapy. While there was a higher peak in urinary symptoms observed in LDR patients, most patients in both groups returned to baseline urinary function by 24-36 months.⁵

A question that remains to be answered is whether patients treated with salvage brachytherapy for radio-recurrent prostate cancer need additional androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) to the pelvic lymph nodes.  

Lastly, Dr. Crook discussed the third and final salvage option for re-irradiation in this patient, which was stereotactic body radiation therapy (SBRT), either for the whole gland or focal treatment. In a study including 56 patients, the margin was 5 mm (3 mm posterior), with the majority of cases receiving 36.25 Gy in 5 fractions. With a median follow-up of 38 months, the study reported 32% grade 3 toxicity overall, with 7% for focal treatment and 41% for whole-gland treatment, indicating that toxicity depends on the treatment volume.

A dose-finding study included 9 patients and used a 30 Gy/5 fraction regimen for whole-gland treatment, with 40 Gy, 42.5 Gy, or 45 Gy/5 to MRI-/PSMA PET-defined gross tumor volume (GTV) in patients who had prior brachytherapy. The margins were again 5 mm (3 mm posterior), with a median GTV of 8.3 cc and a planning target volume (PTV) of 19 cc. No grade 3-5 toxicity was observed, though 100% experienced grade 2 genitourinary toxicity (pain, cystitis, frequency), and 22% experienced grade 2 gastrointestinal toxicity at 24 months. This remains a short follow-up, and still small numbers. Notably, there were no dose-limiting toxicities, and 86% of patients had 2-year biochemical progression-free survival (BPFS), with 42.5 Gy/5 suggested as the optimal dose.⁶

Presented by: Juanita Crook, MD, FRCPC, Radiation Oncologist at The University of British Columbia, Vancouver, Canada.

Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025. 

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