Is there an optimal treatment schedule for high-dose-rate brachytherapy?


Protocols for high-dose-rate brachytherapy (HDR-BT) monotherapy vary. In recent years, practitioners have adopted various schedules for patient and physician convenience.

Jawad et al. reported on the HDR-BT experience at William Beaumont Hospital. They treated 494 favorable-risk patients using three different treatment schedules. Their definition of “favorable risk” was a Gleason score ≤ 7 and clinical stage ≤ T2b and PSA ≤ 15 ng/ml. The three treatment schedules they utilized, the number of patients who received each, and the relative biologically effective dose (BED) were as follows:

  1. 38 Gy in 4 fractions (n = 319) – 1.29 relative BED
  2. 24 Gy in 2 fractions (n = 79) – 1.00 relative BED
  3. 27 Gy in 2 fractions (n = 96) – 1.25 relative BED

Dose schedules #1 and #3 delivered much higher relative dose compared to dose schedule #2. The questions addressed by the study are whether the higher dose is justified by greater cancer control, and whether increased dose levels came at the expense of increased side effects.

After 5.5 years median follow-up for schedule #1, 3.5 years for schedule #2, and 2.5 years for schedule #3, the toxicity outcomes were as follows:

  • No difference in clinical outcomes (cancer control) among the three treatment schedules.
  • Acute (appearing in less than 6 months) and chronic (appearing 6 months or more after treatment) grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) side effects were similar for all treatment schedules.
  • Grade 2 acute GU toxicities:
    • Frequency/urgency: 14 percent
    • Dysuria (painful urination): 6 percent
    • Urine retention: 7 percent
    • Incontinence: 1.5 percent
    • Hematuria (blood in urine): 1.5 percent
  • Grade 2 chronic GU toxicities:
    • Frequency/urgency: 20 percent
    • Dysuria (painful urination): 7 percent
    • Urine retention: 4 percent (urethral stricture: 2 percent)
    • Incontinence: 2 percent
    • Hematuria (blood in urine): 7 percent
  • There was minimal grade 3 GU toxicity
  • Grade 2 acute GI toxicities:
    • Diarrhea: 1 percent
    • Rectal pain/tenesmus: < 1 percent
    • Rectal bleeding: 0 percent
    • Proctitis: < 1 percent
  • Grade 2 chronic GI toxicities:
    • Diarrhea: 1 percent
    • Rectal pain/tenesmus: 0.5 percent
    • Rectal bleeding: 2 percent
    • Proctitis: 1 percent
  • No grade 3 or higher GI toxicity
  • Time to maximal appearance of symptoms was similar across treatment schedules.
  • They did not report ED rates, which are typically low for HDR-BT.

Given the equivalence of cancer control and toxicity with treatment schedule, and the lack of any effect due to increasing the biologically equivalent dose, there seems to be little basis, other than cost and convenience, for choosing among these treatment schedules, at least with the available follow-up reported here.

Aspects of treatment scheduling that affect the convenience of HDR-BT are the number of implantations of the catheters, and the time frame in which the fractions are delivered. William Beaumont Hospital uses a single implantation of catheters for all treatment schedules. Schedule #1 involves a longer (overnight) hospital stay because they wait for several hours between fractions for healthy tissue to recover. It also means that anesthesia must be administered over a longer period.

The California Endocurietherapy Center at UCLA has typically used a different protocol. They deliver 42 Gy in 6 fractions, with 3 fractions delivered in the first week and 3 fractions delivered a week later. This involves two overnight hospital stays, with anesthesia each time. Recently, they added a protocol where they deliver 27 Gy in 2 fractions (similar to schedule #3), but those fractions are still inserted a week apart. While this is certainly a cost reduction for the patient, who can now be treated as an outpatient, the patient is inconvenienced by having to go through the full procedure twice. It is a convenience for the treatment team that no longer has to attend the patient over an extended timeframe.

The William Beaumont Hospital experience demonstrates that HDR-BT treatment schedules can be constructed so as to lower costs and increase convenience for patients and doctors, without sacrificing cancer control or quality of life.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

 

2 Responses

  1. Allen:

    Does the paper by Jawad et al. give any indication of the percentage of the 494 patients treated who would appear to have met NCCN criteria for low-risk disease (and therefore, arguably, didn’t necessarily need early or immediate treatment at all)?

  2. I have not seen the full text, but I think you are quite right to raise that issue for any radical treatment of low-risk patients. I can only hope that recent low-risk patients are encouraged to consider active surveillance. I would note, however, that Alvaro Martinez (then at William Beaumont) has been using HDR-BT monotherapy on favorable risk patients since 1996, and that was well before we had the excellent long-term results on active surveillance.

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