Salvage Low Dose Rate Brachytherapy (LDRBT) after primary LDRBT failure

Although focal retreatment of the prostate using LDRBT has been used after failure of external beam radiation, there have been very few reports of salvage LDRBT after an initial treatment with LDRBT failed.

In a study at the University of Kentucky (UK), Lacy at al. looked at the records of 21 patients who had been re-implanted with seeds.  They all had a bone scan and CT to rule out metastases and locate areas within the prostate that had less-than-optimal seed coverage. Patient characteristics were as follows:

• ·      Initial low risk: 61percent
• ·      Initially intermediate risk: 29%
• ·      Received EBRT with primary LDRBT: 14%
• ·      Received ADT with primary LDRBT : 33%
• ·      Received ADT with salvage LDRBT: 14%
• ·      Age: 59 (median)
• ·      PSA before primary LDRBT: 6.3 ng/ml (median)
• ·      PSA before salvage LDRBT: 3.5 ng/ml (median)
• ·      Time to biochemical failure: 45 months (median)

Seeds were only added to areas that had poor seed coverage. After 49 months (median) follow-up:

• ·      52% were free from a second biochemical failure
• ·      All of the men who were initially classified as intermediate risk suffered biochemical failure.
• ·      All had an initial decline in PSA, reaching a nadir of 0.7 ng/ml at 15 months (median).
• ·      The remaining 48% exhibited biochemical failure at 25 months (median).
• ·      Urinary symptoms were apparent at 3 months after retreatment but improved back to baseline by 18 months.
• ·      Serious side effects comprised bladder outlet obstruction (1 patient), rectourethral fistula (1 patient), and leiomyosarcoma (1 patient).
• ·      Of the 6 men fully potent at baseline, 5 had some deterioration in erectile function by 18 months after re-treatment.

Several other small studies have demonstrated higher rates of biochemical re-recurrence-free survival (Blasko et al., Koutrouvelis et al., Mahal et al., Hsu et al.). Because of the relatively long time to recurrence after re-treatment (25 months median), those studies probably lacked the length of follow-up necessary to detect the re-recurrence.

As with all attempts at salvage treatment after any kind of radiation failure, two conditions must be met before any such attempt is made:

1.     There must be assurance that the failure is local – in the prostate.

2.     There must be assurance that the cancer has not metastasized outside of the prostate.

Multiparametric MRI-targeted biopsies or saturation biopsies (or the two combined) are best for assuring the first condition is met. A more common option has been a random TRUS-guided biopsy. Some of the newer types of PET scans, such as C11-Choline, are best for assuring that the second condition is met. The more common option is the bone scan with CT.

In the UK study, only bone scans and CTs were used to rule out metastasis, and there were no biopsies done to assure that they were treating a local recurrence. They assumed that there were local recurrences in under-covered areas (“cold spots”). It is likely that their oncological outcomes might have been improved by better patient selection. In the University of California San Francisco (UCSF) study, they used MRI/MRS targeting to biopsy areas for recurrence, and to detect cold spots. Two patients had a second focal brachytherapy re-treatment. Five of the 11 patients failed retreatment at 3 years of followup, but 3 of the 5 had negative biopsy results, indicating that the failure was due to remote metastases. Because of better treatment planning possible with the advanced MRI imaging, UCSF also had minimal treatment-related toxicity. Erectile function was maintained with medication in 67% and without medication in 20%.

Good oncological control after LDRBT failure has been reported using salvage surgery and salvage whole-gland cryotherapy; however, sexual toxicity is high with both, and urinary and rectal toxicity is high with salvage surgery. Salvage focal cryotherapy, as well as other focal ablative therapies may increasingly be used for this purpose. As far as other kinds of re-irradiation goes, there has only been a single case report of salvage SBRT after LDRBT failure. Salvage focal HDRBT may be used for this purpose as well.

written April 25, 2016