How would you optimally boost patients with high or very high risk prostate cancer receiving definitive radiotherapy in 2025?

1. Micro-boost is my preferred strategy for dose escalation. The FLAME trial demonstrated a bDFS benefit (Kerkmeijer et al., PMID 33471548). The secondary analysis demonstrated reduced regional+distant metastasis and reduced local recurrence, as well (Groen et al., PMID 34953603). These benefits were achieved without increased toxicity.
   
   
2. Omitting a boost altogether makes sense when the risk/benefit scenario is unfavorable. Examples include: (a) limited life expectancy due to age or medical comorbidities; (b) substantially higher risk of toxicity (tumor abuts urethra, tumor involves bladder neck, or the patient has severe and intractable baseline urinary function).
   
   
3. Brachytherapy boost to the whole gland is supported by ASCENDE-RT (Morris et al...

Dr. @Dr. First Last's answer is thorough and highlights the current state of data well.

What remains unclear is in the era of SBRT, which is increasingly being used in high-risk prostate cancer, and is allowed on trials like NRG GU009, is being tested in NRG GU013, and is supported by NCCN guidelines, what is the true benefit of "boosts".

The field of radiation oncology, understandably, has viewed the modulation of dose as our primary tool to modulate outcomes. So if recurrence rates are not 0%, the simplistic model is to add more dose rather than viewing cancer as a more complex biological process, integrating competing risks, and appreciating the impact of circulating/micrometastatic disease is what primarily drives outcomes. The reality i...

Data suggests a higher dose to a visible lesion leads to better local control. Once the decision is made to do boost, the location and volume of disease can also help decide the boost technique. Microboost like FLAME is driven by location (OAR could be a limiting factor) and the number of lesions (limited to 1-3) while brachy can be offered to all. Among brachy, prefer HDR boost as more control of dose and randomized study suggest less chronic GI effects.

Great answers so far. Agree that best data supports FLAME and Brachy and generally wouldn't offer experimental arms before trials read out (at least when outcomes are generally favorable).

Some additional thoughts that can help individualize for different scenarios

• High volume cores or large DIL: there might not really be such a thing as a microboost for some patients. In that case, if want to dose-escalate there's more evidence for brachy whole gland boost
• Tumor in SVs: These can be hard to implant so if a high-volume brachytherapist or the particular anatomy is not amenable then that's not an option. However, FLAME or microboosting can also be challenging given mobile nature of the SVs. This is a place where adaptive (MRL comes to mind) b...

Great discussions and answers so far!

The answer to this question will and should vary based on the institution and access to high-quality brachytherapy.

I approach these cases by asking myself two fundamental questions (in addition to the typical ones mentioned above):

1. Does this patient have a higher risk of systemic failure vs local failure?
2. Can I confidently identify the DIL (focal) on MRI?

If the risk of failure is more localized (multifocal cores ≥ GG4, EPE, or SVI, no suspicious LN, not very high PSA) and a suitable candidate, I offer an HDR boost. Data suggests a higher dose to a visible lesion leads to better local control. In my experience performing ~100 HDR implants (mono and boost) in the past 18 months, I have encountered ‘zero’...

FLAME SIB, data for std, hypo, and SBRT. ASCENDE-RT outcomes may have been driven by a few high-volume poor brachytherapists… would like a redo comparing (good) brachy with good FLAME.