Radiotherapy for Prostate Cancer: Patient Candidacy & Potential Complications

[Dr. Neil Desai]

I think we all recognize the SCN and the other criteria for going through the number of risk factors, you know, primary pattern, for Gleason seven disease, and, more than 50% positive cores. But the main distinctions nowadays are what to do with MRI guided or MRI targeted biopsies and how that enriches the number of biopsies yielded as well as how to integrate MRI findings, but, certainly an evolving space, facing many of the challenges with stage migration with imaging as any other.

[Dr. Aditya Bagrodia]

And do you kind of get more or less excited for patients that have four plus three equals seven, versus PSA criteria that land them into intermediate risks. So specifically a three plus four equals seven PSA greater than ten.

[Dr. Neil Desai]

Yeah, I think, there's certainly data that, I think, justified a higher concern for risks from primary pattern four as opposed to primary pattern three. Certainly there's data supporting that PSA fluctuations are highly labile, but may not be as important, especially if you regard PSA density as being, maybe lower for a larger gland. And that is still an intermediate risk factor despite that. And finally, if you look at genomic criteria for Legionella classifiers, there's clearly a trend towards, or certainly a strong correlation of higher genomic scores and risk, with Gleason gray group three now, as compared to two, that's more so than with PSA alone.

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[Dr. Neil Desai]

Highly controversial now right? So, I think, any of your elevated PSA's over 10, low density, perhaps they're still reasonable. Now we have the entry of PSMA, that's also FDA approved for this space, and what to do with all these. I think it comes down to pre-test probability and it goes back to what you were saying before. Do you see a high volume Gleason four plus three patient? I think my interest is piqued towards getting more imaging in those patients as compared to someone who barely meets criteria for unfavorable intermediate risk. So pre-test probability by what our nomogram internally or externally use, I think, has to play a role in getting systemic staging, but certainly pelvic imaging is always done in our group.

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[Dr. Neil Desai]

Yeah, I think it comes down to three main issues, right? So the patient-specific factors, disease specific factors, and then your practice patterns and what your expertise and institution will allow or logistics, perhaps. So from a patient per side, I think we're always looking at urinary function, baseline, urinary symptoms, that are obstructive or irritative or mixed, trying to find that if that's important, that will certainly be of importance to radiation therapy and side effect profiles. Secondly, when it comes to co-morbidity, cardiac aspects of metabolic disorders, in interplay with hormonal therapy are important to us, patient preferences, where do they fear most? What do they have to adapt to over the next two years? I think we can all trade stories in what we think is the best modality within radiation and between radiation and surgery and now focal therapies. Clearly patient preference of what they are able to adapt to is so important and probably more important than a lot of what we think is different between modalities.

[..]
Yeah, and we've certainly done a lot of these, I think, there's a handful of publications saying, wait two or three months. There's no real data that anything beyond two months is really that crucial, as long as the patients recovered and hormone therapy gives you that time. So certainly a strong role for optimizing, and hormone therapy can, delay or, or temporize while you are allowed to do that and heal.

[Dr. Neil Desai]
Yeah. I think, baseline sexual potency, about half men have it, half men, don't, you're at risk for losing, that potency with any of these therapies. so have to ask, how important is this to you at this stage in life is a way I put it, put it, And I think that less people will talk to what they classify is a satisfactory sexual function for their life.

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[Dr. Neil Desai]
So for radiation, that's going to be, well, you're going to have to adapt to some urinary bother frequency, urgency, nighttime waking urination issues. Bowel symptoms are still there, but perhaps now with modern radiation techniques, I think the diarrhea aspects acutely during ratio are lesser. Certainly sexual function profiles, perhaps more acute if you're getting surgery. Certainly if you’re adding hormonal therapy to radiation you're gonna see these issues and being open about that discussion, what to see in the first month, second month, et cetera, is very important. The big thing for us is how do you calculate effects of radiation, right? So I'll say, look, all these radiation techniques, there's no clear argument for survival benefit one way or the other. It's going to be about what's going to be least likely to make it so hard for you to adapt to this as your life is totally altered. Furthermore, I have to consider it for radiation. That maybe there is less impact up front, but you have to also consider the late impacts of cystitis or proctitis, in terms of late effects of radiation injury. And so diabetics have you smokers, have to consider this more, so, try to estimate what's a higher risk for those men, and try and assess for them. How are you gonna adapt to that concern? Is it easier for you to take urinary bother now? When this small percent risk you have an injury later, or is it easier for you to take a big hit right now? Let's say surgery, if I'm characterizing that, right. But finding out more about the PSA response, perhaps, and, pathology, and maybe needing radiation later. But having maybe less of the long-term effects upfront. I think just coaching for them, what to expect and their likelihood of needing multimodal therapy is crucially important at this first visit. Beyond that once they get into the question. Okay, this is my baseline risk. Here are my baseline risk factors for harm from therapies obstructed urinary symptoms, et cetera. Now I go into the question of, well choose surgery radiation amongst the radiation factors going on the radiation path, there's internal or external radiation. There's brachytherapy, and recommended seed implants.

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[Dr. Neil Desai]
Yeah, I'm telling them 5-6% rate of significant cystitis requiring a procedure. and that probably if you asked every man that we treated for years after radiation, some blood in the year, and that went away on its own. Probably higher 15% or more, but they're recalcitrant requiring a person all comers. Certainly 5-6% and that kind of starts peaking around year two to three, and then it starts diminishing over time and never goes away. But certainly the incidence rates will go down. The prevalence rates will go down.We've had multiple trials showing that.

The bowel injury rate of proctitis used to be the same number I would argue as under 1% now. To lose your organs would be a never event. That's as you know, happened to my hands. I described this in the case report. We think those contributed to my spacer gel. this should not happen. I think that's uncommon. I would almost worry more about men getting post-operation nowadays for cystitis risks. I think we appropriately started coming down and down on the dose because of that, for post-operation because a nice trial in Europe show that you won't need to go to higher doses anymore and that'll improve the side effect profile there. But cystitis requiring major procedures is certainly 5-6%. Losing your bladder should be under 1% but they do happen. It can't be ignored that secondary cancers for one last point. That's hotly debated based on what data set you look at most of our population registry show under 1%. There are a handful of studies showing just over 1% perhaps room by your baseline risk and smoking in particular.

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[Dr. Neil Desai]
Yeah, we're a big institution in terms of our areas and tuition. Tuition's a big proponent of higher dose per day, radiation as changing the fundamental biology radiation, therefore overcoming these resistance mechanisms. However, we still don't have level one data that says that higher dose per day will overcome resistance. It has worked in other cancers like lung cancer. So there's a precedent for this and renal cancer for that matter, like you noted. But I think we had to prove it. And I think the only proof I have so far that higher dose per day radiation can make a fundamental difference is something called the flame trial. In which a large randomized phase three, in which they said, MR dominant disease gets a higher dose per day of radiation, than the rest of the prostate. That trial improved outcomes by about 10-50% biochemical control without increasing the side effect rate at all. So clearly MR dominant disease PI-RADS four or five is either more resistant or just more important to get cell kill on. And with a higher dose per day, integrated boosting of that area clearly improved outcomes. That's as strong as the data I know of. That hyper fractionation is cracking the nut as if it were on some radiation resistance mechanism that we don’t understand.