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Radiotherapy for Prostate Cancer: Patient Candidacy & Potential Complications

Author Devante Delbrune covers Radiotherapy for Prostate Cancer: Patient Candidacy & Potential Complications  on BackTable Urology

Devante Delbrune • Sep 23, 2022 • 35 hits

Radiotherapy is one of the most common procedures utilized in the treatment of prostate cancer. Due to its extensive use, urologists must carefully consider a variety of factors when determining both patient candidacy as well as treatment courses. While considered an effective treatment modality, radiotherapy comes with the risk of complications that should also be taken into account. 
Urologists Dr. Neil Desai and Dr. Aditya Bagrodia discuss patient candidacy and potential complications associated with radiotherapy in the treatment of prostate cancer on the BackTable Urology Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.

The BackTable Urology Brief

• Prostate-specific factors to consider when determining candidacy for radiotherapy treatment are the patient’s gleason score, the percentage of positive cores, and the pre-test probability of success of treatment.

• Patient-specific factors to consider are urinary function, urinary symptoms, patient medical history, duration of hormone therapy, patient life goals, and treatment preferences.

• Contraindications of radiation therapy include IBD (Crohn's, Ulcerative Colitis), severe hypertrophy of the prostate median lobe, extremely elevated post void residual volume, and connective tissue diseases.

• Potential complications of radiotherapy include cystitis, proctitis, bowel symptoms (diarrhea), bowel injury, and radiation recurrent disease.

Doctor demonstrating prostate anatomy for potential radiotherapy complications

Table of Contents

(1) Prostate & Patient Specific Factors to Consider Prior to Radiotherapy

(2) Contraindications to Radiotherapy in Prostate Cancer

(3) Complications Following Radiotherapy for Prostate Cancer

Prostate & Patient Specific Factors to Consider Prior to Radiotherapy

There are a variety of prostate specificities to consider prior to radiotherapy treatment. While the prostate-specific antigen (PSA) test can assist in the diagnosis of prostate cancer, it is not as definitive for determining treatment. As Dr. Desai points out, PSA values can fluctuate based on the size of the prostate gland, making it inaccurate and relatively subjective when applied to patients. Dr. Desai utilizes more objective measures such as the Gleason score and percent of positive cores. Prime radiotherapy candidates would show a minimum Gleason score of 7 and more than 50% positive cores determined by MRI-guided prostate biopsy. Nomogram modeling may also be utilized to determine the pre-test probability of success for each type of methods of treatment, internal and external. The approach with the highest chance of success is often Dr. Desai's first proposal to the patient.
Beyond the prostate, patients diagnosed with prostate cancer often have other factors that can impact treatment options. Per current recommendations, patients will often undergo 2-3 months of radiation as part of their standard treatment process. Other factors to consider include baseline urinary symptoms, urinary function and cardiac function. The ultimate deciding factor after determining candidacy for treatment is patient goals of care. The decision to undergo the treatment is ultimately the patients. This comes down to the patient's own perception of risks and benefits, along with their individual values in terms of bodily function and lifestyle when deciding between surgery and radiation. 

[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.

[...]

[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.

[...]

[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.

Listen to the Full Podcast

Radiotherapy for Unfavorable Intermediate Prostate Cancer with Dr. Neil Desai on the BackTable Urology Podcast)
Ep 41 Radiotherapy for Unfavorable Intermediate Prostate Cancer with Dr. Neil Desai
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Contraindications to Radiotherapy in Prostate Cancer

Importantly, there are patients who are not candidates for radiotherapy based on interfering medical conditions. Dr. Desai points out that absolute contraindications to radiotherapy for prostate cancer are connective tissue disorders accompanied by immunosuppressants. Other commonly seen contraindications include Crohn’s disease and ulcerative colitis. This is often due to radiation therapy either inducing or increasing the severity of these inflammatory bowel diseases. Another associated contraindication is elevated residual post void volume in the context of alpha blockade. In these instances, the patient is considered high-risk and the prostate issues need to be addressed surgically before radiotherapy treatment. The major factor of concern being severe hypertrophy of the median lobe, as radiotherapy may then be ineffective, requiring future intervention. Assessing these factors and potential contraindications can help to ensure patient success with radiotherapy treatment.
cancer cells or shrink tumors. There are various dosage modifications for external radiation such as conventional fractionation, hypofractionation and hyperfractionated radiation therapy. Fractionation refers to the dividing of the radiation dosage into smaller or larger individual doses. In simple terms fractionation is the degree with which the beams of radiation are split up. An example of this is hypofractionation, which means the radiation dose is less split up, indicating a larger dose is delivered to the selected region during each individual dose of radiation therapy. In teams of the types of fractionation, conventional fractionation is considered the least effective due to the increased toxicity when compared to hypofractionation.

In regards to the treatment process, Dr. Desai’s practice performs external radiation procedures in two phases. The first appointment is performed in clinic where they place gold markers for fiducials in the prostate and a SpaceOAR gel to protect the rectum from prostate radiation The second appointment they have their patients undergo CT and MRI imaging which they make a mold of. The molds are used to determine the angles of approach for radiation therapy. He states this is the standard of care to best minimize radiation to structures adjacent to the prostate.

[Dr. Neil Desai]
Good question. I think it comes down to how close they should be to the no return point? If they have elevated residuals on max alpha blockade, that I think you're asking for badness, I think if you see signs of straining outlet, obstruction about to go catheter dependent, if he gets worse, I think I would like that, addressed before radiation. This is controversial. There's no randomized data as to who's better off, with the chart before or after, certainly are at higher risk. urinary side effects and radiation had a prior TURP. I don't know if it's any better to wait until afterwards. Certainly a urologist as yourself can tell me that doing a TURP after radiation is not fun either.And certainly has side effect risks at the very least, have to consider that these are not the men for intensified radiation approaches such as brachytherapy boost. And those men based on urinary symptom profile, certainly select out those men from that even arguably from SBRT or high dose per fraction radiation, in my opinion, in those cases.

[Dr. Aditya Bagrodia]
Yeah, I think that's insightful. And, you know, there's never going to be a, probably a randomized study of people with a median lobe, unfavorable, intermediate risk pre- post- TURP, et cetera. But also I feel that many times you actually see a clinically significant improvement in symptoms with the introduction of hormonal therapy. You know, obviously you're going to have atrophy of cancer cells, ostensibly, as well as benign prostate tissue. What do you think about that?

[Dr. Neil Desai]
Yeah, certainly I think it's worth a shot. Right? So for our men with larger prostates doing PSI reduction, hormonal therapy may be of benefit. I think it's just worth caution that we don't want to have a situation where we're having wishful thinking that a large median lobe, which will probably not be sensitive to hormonal blockade, will get better with that. I think in those cases it's worth it again, I think just having a good chat about the anatomy that.

This is where the MRI is so helpful, and, knowing what you're trying to shrink down is a cancer in a large gland, or is it just a massive median lobe, that will not be improved by that feature now. Conversely, I think as you've also, well know, urinary symptoms may worsen in an irritative pattern, by ADT. And so I think we've seen men who get better initially then get worse over time. And so, I don't know, there's a magical bullet other than saying, you know, again, post-void residual. The main thing I would say is the closest thing to absolute contraindication is indeed a high, post-void residual before you go into radiation, as opposed to irritative symptoms.

[...]

[Dr. Neil Desai]
You know, you and I, you and I have talked a lot about these median lobes and what to do, how to optimize before radiation. Certainly though a median lobe that correlates in terms of its hypertrophy, to the occurrence of obstructive pattern urinary symptoms in the patient. I don't think it is beyond a radiation oncologist to do a PVR or ultrasound assessment of post-void residuals and their office to get a sense of the Juul trials of alpha blockers to see what kind of buffer you're playing with on this patient.And when they get worse, will you be able to make them satisfied with medication after radiation? I think is a critical, but a substantial median lobe hypertrophy with invagination of the bladder, neck obstructive pathology that has to open your eyes to consideration this patient may be at higher risk for interventions later, and may want to have a discussion with a urologist before the procedure or radiation. In my opinion, if there's a risk of tension.

Complications Following Radiotherapy for Prostate Cancer

Most patients’ first thought when learning about prostate cancer treatment is, “What is the best treatment and how does it work?” When choosing treatment modalities it is important to weigh a number of factors including treatment efficacy, cost and patient goals for quality of life. While the treatment of radiotherapy is effective, it is not without its complications. Following treatment, almost half of men lose sexual potency or face other issues related to sexual dysfunction. Other common side effects include proctitis and urinary issues, such as increased urgency and frequency. Dr. Desai mentions these side effects are also occasionally associated with bowel symptoms such as diarrhea, bowel injury (<1%), and cystitis (5-6%) requiring intervention following radiotherapy. A very complex complication that may arise due to radiotherapy is radiation recurrent disease. This is a condition in which prostate cancer is not completely treated through radiotherapy, leading to disease recurrence and potentially radiation resistant prostate cancer. This condition may be overcome through hyperfractionated radiation therapy, but research in this area is currently ongoing.

[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.

[...]


[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.

[...]


[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.

[...]


[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.

Podcast Contributors

Dr. Neil Desai discusses Radiotherapy for Unfavorable Intermediate Prostate Cancer on the BackTable 41 Podcast

Dr. Neil Desai

Dr. Neil Desai is a radiation oncologist with UT Southwestern in Dallas, Texas.

Dr. Aditya Bagrodia discusses Radiotherapy for Unfavorable Intermediate Prostate Cancer on the BackTable 41 Podcast

Dr. Aditya Bagrodia

Dr. Aditya Bagrodia is an associate professor of urology and genitourinary oncology team leader at UC San Diego Health in California and adjunct professor of urology at UT Southwestern.

Cite This Podcast

BackTable, LLC (Producer). (2022, June 1). Ep. 41 – Radiotherapy for Unfavorable Intermediate Prostate Cancer [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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