News reports (and apparently a media release) have been suggesting that ‘A prostate cancer treatment using permanently implanted radioactive “seeds” doubles rates of 5-year tumor-free survival compared with conventional high-dose radiotherapy.’ Unfortunately, these reports are somewhat — or perhaps very — misleading.
The trial in question is a randomized clinical trial known as the ASCENDE-RT study. ASCENDE-RT stands for “Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy”. And it is absolutely true that this is the first randomized clinical trial of any use of brachytherapy compared to any use of external beam radiation therapy. However, it is very important to understand some key aspects of this trial.
First, the trial was limited to patients who have histologically-documented prostate cancer of clinical stage T1cN0Mo to T3aNoMo (i.e., no sign of seminal vesicle invasion or extension of the cancer into adjacent pelvic organs/structures such as the bladder, let alone metastasis). If the patients are thought to have clinically organ-confined disease, it must be of intermediate risk according to the Canadian consensus definition (i.e., clinical stage T2b or Gleason 7 or PSA between 10 and 20). The patient can have had no prior surgery or radiation or other significant interventional treatment. And the patient’s pre-treatment PSA has to have been ≤ 40 ng/ml.
Second, it needs to be appreciated that the patients weren’t just being randomized to brachytherapy or external beam radiation therapy. The two actual treatment arms of the trial were as follows:
- Arm 1 (the “standard therapy” arm): This comprised a total of 12 months of continuous androgen deprivation therapy (ADT) and, starting 8 months after initiation of the ADT, 4.2 to 5 weeks of external beam radiation (46 Gy in 23 equal fractions) followed by an external beam radiation boost lasting 3.2 to 4 weeks (32 Gy in 16 equal fractions).
- Arm 2 (the “experimental” arm): This comprised a total of 12 months of continuous ADT and, starting 8 months after initiation of the ADT, 4.2 to 5 weeks of external beam radiation (46 Gy in 23 equal fractions) followed by low-dose iodine-125 brachytherapy using permanently implanted seeds of iodine-125 carried out 14 to 25 days after the last external beam treatment.
In other words, this trial only compared two differing types of “boost” radiation after all patients had received a standard combination of ADT + 46 Gy of external beam radiation.
The early results of this study, with 5-year follow-up, were presented at the 3rd European Society for Radiotherapy and Oncology forum, ongoing in Barcelona, Spain.
Here are the core facts as we know them:
- The trial enrolled 398 patients.
- 200 were randomized to Arm 1.
- 198 were randomized to Arm 2.
- After the initial 8 months of ADT, all patients received 46 Gy of external beam radiotherapy to the prostate and the regional lymph nodes.
- At 5 years of follow-up (according to the principal investigator) there was “a large advantage in progression-free survival” in patients in Arm 2 of the trial.
- 8 percent of patients in Arm 2 of the trial experienced severe, late, urinary side effects compared to just 2 percent of patients in Arm 1, but
- “Many of these severe adverse effects were temporary and reversible, or could be ameliorated by procedures.”
- > 80 percent of patients in Arm 2 had few or no long-term urinary side effects.
The study’s principal investigator is also quoted as stating that
Although, to date, overall survival and prostate cancer-specific survival do not appear to differ between the two groups, existing trends favour [the patients in Arm 2] and an overall survival advantage is likely to emerge with longer follow-up.
At best this statement is optimistic. At worst it is very misleading.
When you compare these actual data to the media headlines (see here and here, as examples), you will see that, as yet, there are actually no data at all to suggest that brachytherapy is “better” than external beam radiation therapy. What we have here are some preliminary data suggesting that, in a highly-defined subset of patients who all initially received ADT and 46 Gy of external beam radiation therapy, the patients in Arm 2, who were given a brachytherapy boost using low-dose, permanent seeds (as opposed to a boost of an additional 32 Gy of external beam radiation therapy), had
- A higher (but unspecified) frequency of short-term, progression-free survival
- A significantly greater risk for severe urinary side effects
Whether these results will actually demonstrate an improvement in prostate cancer-specific or overall survival at 10 or 15 years of follow-up is completely unknown at this time. Maybe they will and maybe they won’t. It is impossible to tell. The combination of neoadjuvant ADT, initial external beam radiation therapy with continuing adjuvant ADT, and then a brachytherapy boost may well be a highly appropriate form of treatment for carefully selected patients with high-risk, localized prostate cancer — but it certainly isn’t the only option. Furthermore, as is well understood, high-quality brachytherapy requires considerable skill and experience on the part of practitioners if patients are to minimize risk for serious side effects of treatment.