Questions for the RO for my upcoming video conference regarding options for early salvage treatment (and ADT) after Radical Prostatectomy?

[cyber1]

I had my radical prostatectomy (RP) on 6/3/2019. Given my pathological results (see below for details) and the definite trend in my PSA levels over the last 18 months (see graph below), my surgeon now thinks I should pursue early salvage radiation therapy and I agree, but now trying to decide on the best option for salvage treatment. I have met with a RO who does pencil beam proton therapy and a RO who does IMRT both in San Diego. I have a video conference setup for Friday with Dr. Kishan from UCLA to discuss more salvage options including possible ADT. I am trying to prepare for the consultation. Any suggestions on questions I should be asking? I know there are many options for salvage treatments I have been reading about on this forum besides IMRT and proton like SBRT, VMAT, Hypofractionated radiotherapy, HIFU, Cyberknife, real time MRI guided radiation therapy, Elekta, etc. I know this list is incomplete and probably has things that don't apply, but I am only beginning to learn about them and would like ideas. Thanks for any suggestions or thoughts you have. I want to take full advantage of my time with Dr. Kishan.

Here is my history with my prostate, if it matters. I know there is important information in the pathologic diagnosis which is below but not sure which information in that list is the most critical.

Short version of history:

Prostatitis in spring 2014 went to ER and once to doctor office for catherization because could not urinate. Infection went away after a month but PSA was at 5.8 so had biopsy (4/7/2014) which showed no evidence of malignancy. Stayed on active surveillance. MRI guided biopsy on 12/6/2017, found Gleason 3+3 tumor suspicious (PI-RADS 4) lesion in the middle/left transitional zone in the anterior, Clinical T stage: T1c. Repeat MRI guided biopsy on 1/9/2019 with a PI-RADS 4 lesion in the left anterior transition zone and Gleason 3+4 prostate cancer in 4/6 cores on the left apex lesion, as well as 3/6 cores on the left anterior transition zone targeted lesion. Decided in spring of 2019 to RP. Pre surgery PSA 8.3 (graph of all PSAs in graph below).

Details of final pathology from RP below, this is the short version: Adenocarcinoma of the prostate, Gleason score 4+3=7, Grade group 3

. Involving the right

lateral, right posterior medial, left base and left posterior lateral of the prostate (pT2N0). Percentage of pattern 4: 90%, Percentage of pattern 5: 0%. No Intraductal Carcinoma (IDC) identified. Estimated percentage of prostate involved by tumor: 30%. No Extraprostatic Extension (EPE), Urinary Bladder Neck Invasion, or Seminal Vesicle Invasion identified. Margins: Involved by invasive carcinoma, limited (<3 mm). The left apical margin is very focally positive for tumor. The right apical and bladder neck resection margins are negative for tumor.

Detailed history:

February 2014 could not urinate which was supposedly the result of bacteria infection (prostatitis) and ended up in the ER to get a catheter. Took medication for infection (Flomax and Cipro Adovart), finally went away. Learned how to self-catheterize in case needed to but never came back. Urologist did a DRE which was abnormal and prostate volume was 70 cc. PSA prior had been 5.8 so ordered biopsy.

TRUS prostate biopsy on 4/7/2014. Biopsy showed no evidence of malignancy. Had granulomatous which was attributed to the prostatitis and retention. Weaned off the Flomax and Finasteride. Stayed on active surveillance.

March 2015 PSA 5.2.

September 2015 PSA 4.6

September 2016 PSA 5.2

April 2017 PSA 5.5

September 2017 PSA 6.2

Diagnostic Prostate MRI 11/3/2017.

Targeted MRI guided in bore biopsy of an left apical transitional zone lesion on 12/6/2017.

Findings: Tumor suspicious (PI-RADS 4) lesion in the middle/left transitional zone in the anterior Clinical T stage: T1c; % Positive cores 34%; Gleason 3+3, AUA Risk Low. Prostate volume 84.2 cc. PSA Density 0.074 Ng/cc. Central zone no suspicious lesions. T2 slice #24 (left transitional zone, anterior medial prostate within the apex at 1pm. PIRADS 4 lesion left anteromedial transitional zone. High suspicion for malignancy. No evidence of extracapsular extension or metastatic disease.

Continued active surveillance.

March 2018 PSA 6.2

April 2018 PSA 5.6

August 2018 PSA 6.1

November 2018 PSA 7

Diagnostic Prostate MRI 12/3/2018. Demonstrated a new PI-RADS 4 lesion in the left anterior transitional zone. This is a repeat MRI of the apical transitional zone lesion as well as of the new lesion in the left anterior transitional zone. Volume 90.2 cc. PSA density 0.08 Ng/cc. Central zone normal. Transitional zone: transitional zone T2 signal is heterogeneous with matched areas of restricted diffusion and focally increased perfusion that are not clearly suspicious on T2-weighted imaging and are consistent with changes from BPH.

Targeted in-bore MRI guided biopsy 1/9/2019 of the previously biopsied left apical transitional zone lesion (biopsied: 12/6/2017) and the new left anterior transitional zone lesion.

Findings:

A - Prostate, left transitional zone, anterior, core needle biopsies: Prostate adenocarcinoma, Gleason 3+4 involving 13 of 80 mm (3 of 6 cores)

B- Prostate, left transitional zone, apex, core needle biopsies: Prostate adenocarcinoma, Gleason 3+4 involving 41 of 82 mm (4 of 6 fragmented cores)

Contiguous perineural invasion identified

Comment: Pattern 4 represents 5% of the tumor in both biopsy sites.

FINAL PATHOLOGIC DIAGNOSIS: 6/6/2019 (after Radical Prostatectomy)

A: Fat, anterior prostate, excision:

-Benign fibroadipose tissue.

B: Lymph nodes, right pelvic, dissection:

-Eight lymph nodes with no malignancy identified (0/8).

C: Lymph nodes, left pelvic, dissection:

-Nine lymph nodes with no malignancy identified (0/9).

D: Prostate, radical prostatectomy:

-Adenocarcinoma of the prostate, Gleason score 4+3=7, involving the right

lateral, right posterior medial, left base and left posterior lateral of

the prostate (pT2N0).

-No extraprostatic extension identified.

-The left apical margin is very focally positive for tumor, see comment.

-The right apical and bladder neck resection margins are negative for

tumor.

-No angiolymphatic invasion is identified.

-The seminal vesicles are negative for tumor.

-See synoptic report.

COMMENT:

PROSTATE GLAND SYNOPTIC REPORT: Radical Prostatectomy

Procedure: Radical prostatectomy

Prostate Size:

Weight: 100 g

Size (centimeters): 6.0 x 6.0 x 5.5 cm

Histologic Type: Acinar adenocarcinoma

Histologic Grade: Gleason Pattern

Primary Gleason Pattern: Pattern 4

Secondary Gleason Pattern: Pattern 3

Tertiary Gleason Pattern: N/A

Total Gleason Score: 7

Grade Group: Grade group 3

Percentage of Gleason Patterns 4 and 5 (applicable to Gleason score ?7):

Percentage of pattern 4: 90%

Percentage of pattern 5: 0%

Intraductal Carcinoma (IDC): Not identified

Tumor Quantitation:

Estimated percentage of prostate involved by tumor: 30%

Extraprostatic Extension (EPE): Not identified

Urinary Bladder Neck Invasion: Not identified

Seminal Vesicle Invasion: Not identified

Margins: Involved by invasive carcinoma, limited (<3 mm)

Focality: Unifocal

Location of Positive Margin: Left apical

Treatment Effect: No known presurgical therapy

Lymphovascular Invasion: Not identified

Perineural Invasion: Present

Extranodal Extension: N/A

Pathologic Stage Classification (pTNM, AJCC 8th Edition)

Primary Tumor (pT): pT2: Organ confined

Regional Lymph Nodes (pN): pN0: No positive regional nodes

Number of Lymph Nodes Examined: 17

Number of Lymph Nodes Involved: 0

Additional Pathologic Findings:

High-grade prostatic intraepithelial neoplasia (HGPIN)

Nodular prostatic hyperplasia

Ancillary Studies: Not performed

Comment: The left apical margin in this specimen is very focally positive

for prostatic carcinoma. However, the anterior prostate fat is negative for

the tumor. Therefore, the real final resection margin could be negative.

Clinical correlation is recommended.

[Tall_Allen]

Amar Kishan is excellent! I've heard good things about Rossi from a couple of his patients. Dr. Kishan is running a randomized clinical trial of his new MRIdian linac, which he hopes will have lower toxicity than his VMAT linac. Fortunately, at your low PSA, there is no need for adjuvant ADT. Whether the pelvic lymph nodes require treatment is a judgment call. Dr Kishan was co-author of a guideline recommendation to only use hypofractionated salvage radiation during the pandemic. I don't know if Rossi does that with protons.

Here are some questions to ask:

prostatecancer.news/2017/12...

[cyber1 in reply to Tall_Allen]

Hmm... So are you saying he is running a the randomized clinical study between the VMAT linac and MRIdian linac? If I participated I would have a 50/50 chance of getting either one. I thought the Viewray MRIdian linac was already being used by UCLA and it was one of the reasons I ended up contacting Dr. Kishan.

Do you know if the VMAT linac has a higher or lower toxicity compared to say pencil proton or IMRT?

It is interesting that you mentioned treating the pelvic lymph nodes. Did you see something in my pathology report that made you consider that as a possibility?

You mentioned hypofractionated salvage radiation, what about SBRT? Did I read somewhere that you received treatment yourself? Or is that only for primary treatment, not for when you are treating the bed as salvage treatment?

Are there really any other options for salvage treatment I should be considering?

As an example, I ran into Cyberknife which I guess is related to Stanford. In my google search I found a Cyberknife facility within a few miles of my home, and I just called it and they said they no longer use that machine and how they use a newer version called TrueBeam. Apparently they use this treatment as SBRT. I am sending them my information to them now to figure out if that might be an option.

I guess that is my point, the options seem almost endless, even though I know there is a limited list of options.

Is there a list of possible SRT treatment options, like I am trying to find?

And do you have any thoughts about which of those types of treatments are considered the most cutting edge/effective? I have a feeling that part of the problem is these newer forms of treatment (like MRIdian linac or Elekta or Cyberknife or TrueBeam, etc), even something like pencil beam proton which has been around for a while, does not yet have randomized clinical studies so how effective or its level of toxicity which makes it hard to recommend. Regardless I would like your opinion.

[Tall_Allen in reply to cyber1]

No one knows if the MRIdian has higher or lower toxicity than the VMAT system - that's why he is doing the clinical trial. It has never been compared to protons. In fact, X-rays (on any delivery system) have never been directly compared to protons (pencil beam or otherwise). Salvage protons is a relatively new thing. So far, indirect comparisons between X-rays and protons show no difference, at least for primary therapy:prostatecancer.news/2016/08...

Be careful about embracing new technologies - they are not always better, even though they may sound like good ideas. And there is a LOT more to determining toxicity than just the delivery technology. VMAT is a kind of IMRT. The arc delivery just makes it faster. Sometimes, faster is better because there is less time for the soft tissue to move around. However, MRIdian is a very slow process because it continually lines up the contours of treated area with the plan. It is similar to Tomotherapy, which creates a continuous CT scan as it delivers X-rays.

Dr. Chris King, who mentored Amar Kishan, first used CyberKnife at Stanford to treat prostate cancer in 2003. When he came to UCLA, he changed to Truebeam with RapidArc (a VMAT linac). He prefers the VMAT system, but results are very similar. Kishan uses Truebeam with RapidArc or MRIdian for salvage radiation. The platform has less of an impact than you may think. The really critical things are the decisions and care the RO puts into the treatment plan.

Your high percentage of pattern 4 is something to consider in deciding whether pelvic LNs require treatment.

[cyber1 in reply to Tall_Allen]

Thanks, I really appreciate your thoughts.

Interestingly so far, neither the regular x-ray IMRT RO or the proton RO mentioned treating anywhere other than the prostate bed. It will be interesting to see what Dr. Kishan says.

Based on what you are saying, it sounds like the TrueBeam system that is now being used right down the street from my house, could be the same or very similar to what UCLA uses.

This almost brings me back to what I was thinking in the beginning. Given the lack of controlled studies showing the efficacy or toxicity of these many types of treatments, the most important variable might be the doctor and technologists who actually perform the treatments.

Is there any kind of list for all of the various types of treatments for SRT?

You did not mention your thoughts about SBRT for my SRT? And would your answer depend on the type of system I pick (i.e. IMRT vs. Proton vs. UCLA whatever they offer me tomorrow vs. TrueBeam) which are the four options I am currently considering?

BTW, the link you provided for questions to ask was incredibly exhaustive. Not sure I will have time to ask all of those questions, but it is certainly a perfect place to start.

Thanks.

[Tall_Allen in reply to cyber1]

When you say "treatment types," are you asking about the various linacs? There have been several comparative studies of various linacs, all showing that results are similar. That is not a high leverage concern, imo. SBRT is seldom used for salvage, but may be used more during the pandemic. Hypofractionation is probably a good idea.

Is Stanford "down the street?" If so, Mark Buyyounouski is the man to see.

stanfordhealthcare.org/doct...

As for LN involvement... Your very low PSA argues against it, as does the focal positive margin. In fact, in the SPPORT trial (below), men with low PSAs did not benefit from salvage LN treatment. However, I expect few of them had 90% pattern 4. Your PSA is also too low for anything to show up on a PSMA scan.

prostatecancer.news/2018/10...

[cyber1 in reply to Tall_Allen]

When I say different types, in my mind it means what the RO would use to treat me. So I guess I mean type of machine which I don't exactly understand in my mind yet.

Is this a way to categorize treatments?

Type of radiation:

x-rays

protons

electrons

sound

??

Then:

How you guide that radiation to the target area

How you concentrate the radiation

Can you adjust the beam to the target area in real time

??

Is that even close?

Not sure what you meant by "high leverage concern"?

Is there a reason why SBRT is not typically used for SRT?

Regarding living near Stanford, no I live in San Diego and the place I called used to use a Cyberknife machine and they said they now use the newer version which she said is the TrueBearm machine. The RO that uses TrueBeam at this location for prostate treatment used to work at the California Proton Center but now works at this location. His name is Dr. Patrick Linson.

Thanks for the links. I will read those next. I certainly don't want to wait to do my salvage treatment until my cancer can be seen on a PSMA scan.

[Tall_Allen in reply to cyber1]

What I am trying to impress upon you is that your concern with the type of linac is a very minor concern - they all do an excellent job these days (as long as the machine was designed in the 21st century). The important (high leverage) concerns are the ones in the list of questions - RO's experience, adjuvant therapy, treatment dose and volume, and expected side effects.

The kind of radiation, protons or X-rays, does not seem to make much of a difference either. Electrons and ultrasound cannot be used for SRT.

What is important is the RO and the plan he creates. The job of the RO, working with his physicist, is to design a treatment plan that delivers a cancer-killing dose of radiation to the cancer while minimizing the dose to the organs at risk (mainly, bladder and rectum). They set dose donstraints and choose a plan that meets them as well as possible, given your anatomy. Nothing is tampered with "on the fly." It is all programmed into the computer that runs the linac. In fact, you won't even see your RO during each visit, unless he wants to say hello. The radiation tech is always there to make sure your bladder is full, your rectum is empty, and the tattoos are properly aligned at the start.

SBRT is more precise than is useful for SRT because such a wide area is treated and the precise location of the cancer is indeterminate. The prostate bed is full of loose tissues that move easily, so when there are only 5 big doses, some beams may miss the cancer or hit organs at risk. There is the same concern with protons. But both are being tried experimentally with SRT. Moderate hypofractionation (about 26 treatments) has tested well and is certainly a good idea during the pandemic.

I've heard that UC San Diego has a very good radiation oncology department. If that is close to home, it makes more sense to go there. Commuting all the way to LA every day will get tiresome.

[cyber1 in reply to Tall_Allen]

So if all of the radiation therapy I have been looking at are really just different versions of linac x-ray machines (except the proton system) and you are saying the difference between the different types of linac machnies is not that big of a deal. Okay, what about the way the machines aim their linac radiation?

I thought there were types of MRIgRT machines that were completely computer automated, that adjusted the radiation beams in real time during the radiation treatment without human intervention based on the real time MRI images of the soft tissue. So they supposedly address the intrafractional and interfractional motion issues. Is that not true?

Are fiducials ever used in SRT for the prostate bed?

If it is not true that there are guided RT machines that takes the human out of the equation and adapts on the fly to motion of the patient, than the difference seems to boil down to the RO and his team which is essentially what you have been saying. How well the RO and his team sets up and executes the plan of treatment. So how do you judge the RO then? How they answer the questions you provided? I don't know what the best plan of treatment is, how much radiation to give etc. Is there a rating system (yelp like) for RO and their systems? I don't feel comfortable enough to be interviewing RO to figure out who is the best at providing my SRT. I have met with two so far and both seem fine but I did not have your questions and I certainly did not have the knowledge I have now (although as the say, a little knowledge is a dangerous thing). I know I am not even close enough knowledge wise to be judging these ROs. I don't like the idea of using my gut reaction.

[Tall_Allen in reply to cyber1]

The machines are similar in the way they deliver radiation, although there are differences - some are step-and-shoot, some are arc, some are gantryless, some have smaller leaves on their multileaf collimators, some use multifield fixed directions. For imaging, some use cone beam CTs, some use stereo Xrays, some use MRIs, some use the same Xrays used for treatment. For alignment, some use fiducials, some use RT transponders, some use soft or hard-tissue landmarks, some use gating. Some check continuously, some check intermittently, all check at least once per session. They are all pre-programmed and once locked in, do not require human intervention, which would create errors. None of this matters to the patient. It's like trying to judge a carpenter based on whether he uses Skil tools or Black and Decker. What matters to us are two things: (1) did it deliver enough radiation and in the right place to kill the cancer, and (2) did it do it with a minimum of toxicity.

I understand why you are trying to make a decision based on technology - it's easy to understand how a machine works. It's much harder to understand what your RO does. Your RO has years of training and (hopefully) years of experience. You will never know what he knows. Did you learn how to operate using a Da Vinci machine before your surgery?

You don't judge an RO by his equipment, you judge him by his expertise, his track record, the amount of time and care he seems to take, whether he keeps up with (or has added to) the state of the art, and whether he seems to acknowledge your concerns. The questions are as much for your edification as to help you make a judgment about which RO. I think you are beginning to understand how much there is to know about all this, and the questions are designed to give you a healthy appreciation of that. I think you will become less anxious as you learn more.

Some try to use fiducials for SRT, but most don't. There is nothing for fiducials to lock onto in the soft tissue of the prostate bed. Instead, they site a long bone or some soft tissue landmark. (BTW - this is another reason not to use SBRT for SRT). Ask the RO what landmarks he uses.

[cyber1 in reply to Tall_Allen]

You said that some check continuously, when those types of machines check don't they adjust for intrafraction motion by changing the direction of the radiation beam? It seems like if they check they do it for a reason which seems like it would either be to adjust the beam to stay on the target due to motion during the treatment or it would automatically stop the treatment if the movement is too much. But either way it seems like both scenarios are better than just checking once at the beginning of each treatment and comparing it to a scan that was taken a couple of week previously. That seems like it would mean those types of machines would not account for any intrafractional motion and given you said the prostate bed is prone to movement it seems like a machine that can adjust continuously would be superior. I get your analogy with Skil vs. B&D, the person using those tools is way more important, but with the new CNC machines that my son uses for his wood working it is no longer his ability to use the tool, but his ability to make a good CAD (which I think is analogous to the RO and team setting up the treatment plan and programing the computer running the machine). Once that is the way he wants it, the machine cuts out his wood better than he ever could with any brand of hand tool.

I guess where I got hung up on the technology as you said, is listening and reading all of the stuff out there that talks about their latest and greatest machines that can deliver the radiation more accurately to the target area with less toxicity to the surrounding tissues. It is like listening to advertisements on TV. Everyone is pushing their product and telling you why their product is superior and since doctors don't advertise they advertise their technology.

So if my dream of finding a new machine/technology that will deliver the radiation more accurately is just a pipe dream, is there a yelp version or something else online somewhere that compares RO?

[Tall_Allen in reply to cyber1]

You are putting your mental energies into low-payoff pursuits. I guess it is fruitless of me to try to convince you to devoting those energies instead into finding a good RO instead of the perfect machine.

[cyber1 in reply to Tall_Allen]

No I agree with you, that is why I ended that post with "is there a yelp version or something else online somewhere that compares RO?" The only reason I have spent my energies on the machines is because it is much easier to find studies and research about the machines online than on the ROs.

I would love to spend that time on researching the ROs, I just have not had a lot of luck online so far and thought maybe there was something out there, like my kids use to find out about possible professors to take classes from. When I was young no such resource existed, now they go straight to the website and immediately find out essentially everything they need to know about a professor before signing up for classes each semester. I could not believe it when they showed it to me, but something like that for ROs would be awesome. I know this is 'different' but that does not mean it should be, or does it? What is more important....

[Tall_Allen in reply to cyber1]

There are some resources. This mentions some:prostatecancer.news/2017/12...

Nothing beats making appointments and talking to them. You have to find the doctor who is right for you, not someone else.

[cyber1 in reply to Tall_Allen]

I have been reading about the pelvic lymph nodes.bmccancer.biomedcentral.com...

It talks about the importance of lymph node dissections during the RP. It says,

"Pelvic lymph node dissection (PLND) is one of the most important steps in radical prostatectomy (RP). Not only can PLND provide accurate clinical staging to guide treatment after prostatectomy but PLND can also improve the prognosis of patients by eradicating micro-metastases."

They don't specifically say it (probably because it is a given and everyone should know this) but when a PLN is dissected they are saying it was removed and therefore cannot grow prostate cancer, correct? That sounds really good.

It went on to say:

"The relationship between the number of lymph nodes resected and prognosis:

Heidenreich et al. [19] reported that e-PLND could significantly reduce the cancer-specific mortality (CSM) of prostate cancer (23% reduction in N + and 15% reduction in N0). Many researchers have tried to reduce the number of resected nodes to reduce postoperative complications while ensuring tumor control. JI JD et al. [27] reported data on 360 patients with localized prostate cancer who underwent open RP. A comparison of the progression-free survival after s-PLND (obturator and external iliac nodes) to that after e-PLND (obturator, internal iliac, external iliac and common iliac nodes) revealed that the 5-year progression-free survival rates after s-PLND and e-PLND were 90.1 and 91.3% in the low-risk group, respectively. There was no significant difference between the survival rates. In contrast, there was a significant difference in the intermediate risk group (73.1% vs. 85.7%, P = 0.042) and in the high-risk group (51.1% vs. 71.4%, P = 0.036). Abdollah et al. [28] reported data on 315 cases of lymph node metastasis. They found that the ratio between the number of resected lymph nodes and the 10-year survival rates without CSM was 8:74.7%, 17:85.9%, 26:92.4%, 36:96% and 45:98%. CSM was significantly reduced when the number of resected lymph nodes was 14 or more."

The article also said,

"Mattei A et al. [24] reported that e-PLND could remove 75% of the lymph nodes with potential metastasis risk. Joniau S et al. [25] reported that e-PLDN+ presacral nodes could remove 97% of the lymph nodes and 88% of the metastatic lymph nodes. Our group has previously reported data on 103 patients who underwent RP+ e-PLND [26], and we found the following lymph node metastasis rates: internal iliac nodes, 59% (13/22); obturator nodes, 50% (11/22); external iliac nodes, 36% (8/22): presacral nodes, 14% (3/22); and common iliac nodes, 5% (1/22) (P < 0.05). The lymph node metastasis density was 28% (21/74), 37% (19/53), 25% (8/32), 33% (3/9) and 20% (1/5) for the internal iliac, obturator, external iliac, presacral, and common iliac nodes, respectively (P > 0.05). We propose that the sentinel lymph nodes of prostate cancer, including the obturator, external and internal iliac nodes that have high metastasis rates and densities, need to be removed during PLND. If suspicious lymph nodes are found in the presacral region, they should also be removed, but iliac area does not need regular dissection." (I added the underlining for emphasis)

Given all of this, which you probably already knew, for my case where the pathology report from my RP says I had 8 lymph nodes from right pelvic, dissected and 9 lymph nodes from the left pelvic area dissected, all with no malignancy identified. So if I am correct that mean I now have 17 less PLNs. Based on this article the average number of PLNs is around 40 (there was considerable variance) and given about 30 of those nodes seem more likely to house the cancer (the sentinel ones) that would mean the surgeon might have removed about half of the PLNs that might potentially harbor prostate cancer.

After reading this article I am surprised that the pathology report does not better describe where those 17 PLNs were removed from.

This article did not talk about the side effect and issues with radiating the PLNs. The study you provided me was encouraging for SRT including the pelvic area with ADT but again for people whose PSA is higher than mine. It said, "the researchers found that the benefit of salvage whole pelvic treatment and ADT was not maintained in men with very low PSA (<0.2)".

This reminds me of the ADT studies that show for men with higher PSAs ADT can be helpful but there is no evidence yet that it can also help those with low PSAs like mine.

I guess for both options, ADT and radiating the pelvic area is a pro/con decision because both have potential to increase the chances of a cure or at least better survival but they obviously have potential side effects both short and long term.

I will be curious what Dr. Kishan says today.

Thanks for making me aware of some of the research out there.

[cyber1 in reply to Tall_Allen]

I had my video conference with Dr. Kishan Friday afternoon. As I prepared for the meeting I knew that this was really informational only because I was not going to go up to UCLA 35 times for radiation (it is a 2 hour drive each way) and I still have a child in high school so I was not going to move up there for two months. But during our course of conversation he mentioned a clinical trial he is running. I think it is different than the RCT you mentioned because it is a clinical trial (not a randomized trial) looking at the effectiveness of doing SBRT for SRT using his newest MRI guided ViewRay machine. I was intrigued and after the teleconference he sent me paperwork to complete if I wanted to participate. Anyway, the idea of only driving up there five times is definitely reasonable, I might even stay up there, but either way using the MRIgRT ViewRay for SBRT sounded interesting and something I am now considering.

I know there is not much out there currently on using SBRT for SRT. Did you receive SBRT for your primary treatment? What are your thoughts about this clinical trial and the idea of participating in it?

[Tall_Allen in reply to cyber1]

Yes, I'm aware of his clinical trial of SBRT for SRT. My feeling (similar to protons) is that SBRT may be too precise for such a large area where the location of cancer cells is indeterminate. On the other hand, SBRT provides a biologically effective dose that is higher than that normally given for SRT, and there is some evidence that such a larger biologically effective dose may be more effective. Here's an article about that trial that discusses some of the issues:

prostatecancer.news/2018/01...

[cyber1 in reply to Tall_Allen]

Thanks, this is definitely the clinical trial. I thought this was interesting, first it said, "All patients will receive 34 Gy in 5 fractions to the prostate bed" but then it said "The prostate bed dose is biologically equivalent to 85 Gy using conventional fractionation (about 1.8 Gy per fraction). It is much higher than the typical salvage radiation dose of 67 Gy - 72 Gy in 37-40 fractions. It also exceeds by about 9% the dose used in a trial of moderate hypofractionation (discussed here)."

Do you know how they determined that a dosage of 34 Gy given over 5 fractions of 6.8 Gy is equivalent to 85 Gy using conventional fractionation?

It seems like getting less total dosage 34 Gy vs. 70 Gy would be a benefit for OAR as long as it kills the intended target, which as you said is unknown to begin with, but hopefully still in the prostate bed and hopefully with the MRIgRT it is more likely to hit the bed and have less OAR.

I think Dr. Kishan said, to my surprise, that I could get further radiation to the pelvic nodes in the future if needed.

He also said that he would not recommend ADT or radiating the pelvic nodes given what he knows, but he was surprised that I had not already had a Decipher test because he said that would influence his recommendation on ADT.

[Tall_Allen in reply to cyber1]

Yes I know how I calculated it, but trust me, it is correct. A forum like this is not conducive to explaining the mathematics of radiobiology.

While the biologically effective dose to OAR is lower, the danger, as I said, is inadequate dosage to kill the cancer in the broad prostate bed. What good is sparing tissues if you do not kill the cancer? I do not know that the MRIdian is "more likely to hit the bed and have less OAR." That is certainly the hope, but may not be the case. SBRT is especially risky (on any platform) because you get fewer chances to get it right.

Yes, you can get the pelvic LNs done later.

With 90% pattern 4, I really don't think that Decipher is likely to tell you much. To my mind, it is clearly a "high risk" tumor (even though it is officially GS 4+3). Perhaps remind Dr. Kishan of that fact in a f/u email, and ask if he agrees.

[cyber1 in reply to Tall_Allen]

When you say, 'yes I know how I calculated it" I am not sure what you are referring to? I did not think I talked about how you calculated anything. What I did refer to was how does 5 doses of 6.8 GY equivalent to 85 Gy of conventional radiation. I am sure that is complicated, but just wondered if you knew anything about this or somewhere I could read about this equivalence.

I hear you about not hitting the right target as well as not even knowing exactly where the cancer is at this time, but I am hopeful that at least hitting the prostate bed would benefit from MRIgRT. To me ASSUMING the MRIgRT works as designed it would be better than conventional radiation. I am saying assuming because there are no RCT yet, but that also does not mean it is not true.

Regarding, the pattern 4 of 90%. I don't understand that rating at all. I thought I understood the Gleason score, but now I am confused with how that relates to the pattern percentages and "Grade Group". My Grade Group is 3 which is what I believe Dr. Kishan referred to. I will ask him again about these patterns and Grade Group again.

Here is what my path report said compared to someone else who has been messaging me. What am I not understanding is how his Grade Group is 5 and mine is only 3:

My path says:

Total Gleason 7:

Grade Group: Grade Group 3

Percentage of Gleason Patterns 4 and 5 (applicable to Gleason score ?7):

Percentage of pattern 4: 90%

Percentage of pattern 5: 0%

This other person's says:

Gleason Score: 4+5 = 9/10

Grade Group: 5

Percentage of Gleason Pattern 4: 80%

Percentage of Gleason Pattern 5: 10%

I guess I don't understand these two different reports. I thought Gleason 7 (even a 4+3) is like in another world compared to a Gleason of 9 or 10 and yet if I understand these two different reports I see it this way:

My pattern:

10% pattern 3, 90% pattern 4, 0% pattern 5

Other's pattern:

10% pattern 3, 80% pattern 4, 10% pattern 5

For both of these since the pattern 4 and 5 adds to 90% I am assuming the remaining 10% pattern is pattern 3.

Any way, it seems to me that when the pattern changes from 4 to 5 it is not a binary one. I would think this pattern is a continuum. So when the person does the pathological report from the slides these two reports are very similar. When they did the pathology of the slides from the surgery the tissue they actually examined could have been just off from a section that might have had a little bit of pattern 5 (10%). So why are the Gleason scores so different given what seems to me to be a small amount of difference in the patterns.

Not to mention, why is mine Grade Group 3 and the other Grade Group 5? Based on the predominant pattern both should be Grade Group 4, but that is not the case, obviously there is something I don't understand here. I looked online but could not find much on Grade Group.

So to me these two patterns are very close, and yet one is a 4+3 and the other a 4+5 and come out to very different results as far as a total Gleason score which I thought was really important, but the way I see it now, the differences in those Gleason scores are not that big of a deal (but I know that is not true, so I am missing something here).

[Tall_Allen in reply to cyber1]

I was responding to your question: "Do you know how they determined that a dosage of 34 Gy given over 5 fractions of 6.8 Gy is equivalent to 85 Gy using conventional fractionation?" "They" is me.

"To me ASSUMING the MRIgRT works as designed it would be better than conventional radiation." That is not necessarily true, for the reasons I tried to explain. I think Kishan uses bony landmarks in either case - I don't see an advantage of one machine over the other. It is not like primary radiation where the whole prostate gland is the landmark for MRIdian.

In your case, 90% of the tumor was pattern 4, 10% was pattern 3. That means that your Gleason score is 4+3, which is Grade Group 3. If it were 95% pattern 4 and 5% pattern 3, it would have been reported as Gleason score 4+4, Grade Group 4. The difference between 90% pattern 4 and 95% pattern 4 can be within the margin of error due to the observer or the slice thickness. That's why I think you may be better off being treated as if your Gleason score indicated adverse pathology.

Your friend who had 80% pattern 4 and 10% pattern 5 is Gleason score 4+5, which is Grade Group 5. On whole-mount pathology, the first number of the Gleason score is the most prevalent Gleason pattern; the second number is the highest Gleason pattern over 5%. (There is a tertiary pattern reported if it is less than 5% but higher grade than the first two.)

The Gleason Grade Groups do make a big difference in prognosis. It is important to get an experienced pathologist looking at it. It is less difficult to decide using whole mount (post-prostatectomy) than biopsy cores.

[cyber1 in reply to Tall_Allen]

Wow, I had no idea the 'they' was you. Cool. So based on this statement, getting 5 doses of 6.8 Gy equates to essentially 47 doses of 1.8 Gy, is that true? That seems like a plus just based on this.

Regarding how the prostate bed is targeted, I don't know, I will ask Dr. Kishan.

Regarding the scoring system. I agree with you that essentially (within the margin of error as you said) I am Grade Group 4 with a Gleason of 8. Given this shouldn't I/they be considering radiating the pelvic nodes?

BTW, both of these pathologic results were from whole mount. Regarding the pattern 5 vs. 4, would it not be true that the difference is on a continuum and so it seems like with a 90% pattern of 4 the reality is, these results are really close to having some pattern 5? Or does turning pattern 4 cells into pattern 5 take a considerable amount of time or something else and it is kind of a binary thing where the change is all or nothing, like a light switch. I just think there is a good chance I already have some pattern 5.

Finally, in the piece you gave me a link to:

prostatecancer.news/2016/08...

You said, "With its (SBRT) pinpoint accuracy, many radiation oncologists are using it for primary treatment at doses up to 8 Gy per treatment session. But that is also its drawback for salvage therapy – it may be too accurate. Because we don’t know exactly where in the prostate bed the cancer may be hiding, IMRT or 3D-CRT – radiation technologies with less abruptly ending margins – have been traditionally preferred."

Why did you say SBRT is more accurate? I thought the difference between SBRT and all of the forms of hypofractionation and conventional fractions was just how much energy is delivered to the target area per fraction. Which brings up the whole idea of what is a gray unit? When I looked it up it says 1 gray = 1 Joule/kilogram. So does that mean 1 Joule of energy is delivered per kilogram of tissue that is absorbing it? My prostate weighed 0.1 kilogram so if it was radiated with 70 Gy I guess that means it would have received 0.1 Joules of energy total for my intact prostate, where with the prostate bed, I am guessing the mass is much less, maybe 100 times less (like 0.001 kg, I googled it but could not find anything) so the amount of energy delivered to that area would be proportionately less. Also since the total would only be 34 Gy with SBRT the amount of energy delivered to the prostate bed would be less by a factor of two on top of the reduction in energy due to the smaller mass. My point though is how does the amount of energy delivered due to the radiation relate to the accuracy? I thought that had to do with the machine and how good the IGRT or MRIgRT was in getting the energy to the right place, ie. be more accurate. But it seems like you are saying the accuracy has something to do with it being SBRT. Am I misunderstanding this.

Also, this reasoning is exactly what both my surgeon and urologist said about conventional photon radiation as potentially being better than proton therapy. They both said that proton therapy because of its Bragg Peak distribution of energy potentially spares the surrounding organs more than traditional photon radiation but that could be a bad thing because those surrounding organs might be housing the PCa so given we don't know where the PCa is, why not go with something less accurate. If I understand you, you are saying a similar notion applies to the SBRT that compared to less accurate conventional photon therapy but again isn't SBRT just a more energetic form of conventional photon radiation?

[Tall_Allen in reply to cyber1]

"That seems like a plus just based on this." More radiation is only a "plus" if it is not more toxic and does a better job of killing the cancer.

"Given this shouldn't I/they be considering radiating the pelvic nodes?" That's what I suggested talking to Dr.Kishan about - perhaps pointing out the 90% pattern 4. I don't know if you did this at your telemeeting. As I said earlier - it is a judgment call, given the upside of your initially undetectable and still low PSA. I would trust his judgment. He has had a lot of experience treating risky cases.

"would it not be true that the difference is on a continuum and so it seems like with a 90% pattern of 4 the reality is, these results are really close to having some pattern 5?" There are only 3 cancerous Gleason patterns - 3, 4 and 5. Expert pathologists can distinguish them. That's where experience and expertise comes in, although it is easier to distinguish on whole-mount than on biopsy. As I said, interobserver disagreement and slice thickness may make a difference between 90% and 95% pattern 4. It won't change pattern 4 to pattern 5.

"Why did you say SBRT is more accurate?" Because intrafractional tracking is more accurate than interfractional tracking. That's what the "stereotactic" stuff is. SBRT can be specified down to a fraction of a millimeter and treatment margins are small to non-existent (on the rectal side). But aside from the image guidance, SBRT errors in beam delivery due to organ motion can have a significant impact. With IMRT, errors due to organ motion have less of an impact. As I tried to convey earlier, your concern should be with cancer-killing and toxicity. Try to stay focussed on those two things. You are getting lost in the minutiae.

[cyber1 in reply to Tall_Allen]

Thanks again. I mentioned the 90% pattern 4 but I did not have the exact results in front of me at the time; however, Dr. Kishan said he still did not recommend treating the pelvic nodes, but I will ask again. I will word it in a way that says given my high level of pattern 4 and the fact that I am within the margin of error to having a Gleason score of 8, is it not worth treating my pelvic nodes. I will tell you what he says.

Regarding the accuracy that makes sense to me. I did not know that the "stereotactic" stuff had to do with the ability to track the intrafractional motion, I thought the intrafractional motion was tracked using MRIgRT and the stereotactic part was related to the amount of dosage. So does that mean hypofractionation is not as accurate as SBRT?

Given what you are saying about the really important question I should be asking, i.e. what is potential for being better at killing the cancer cells and giving less toxicity, both of which I have read is a potential benefit of SBRT, I am now leaning toward doing the SBRT as part of the clinical trial. If Dr. Kishan and Dr. King both think it has potential for SRT it is hard to not take advantage of their knowledge and many years of experience. As I read on one of your posts on Prostate Cancer News, Reviews & Views you tried SBRT for primary treatment when it was also very young and did not have a well proven track record. I would say ten years later with the experience both of these doctors, not to mention others from around the country who use SBRT and know its pluses and minuses, if they think it is worth using to treat SRT who am I to disagree?

BTW, I asked my surgeon here in San Diego about getting Decipher testing and his nurse will get back to me tomorrow. What do you think about that test?

[Tall_Allen in reply to cyber1]

Just because there is a clinical trial, doesn't mean that those doctors endorse SBRT for SRT. They are both good, objective scientists - they are running the trial because they want to find out - not to reinforce pre-existing prejudices. The state-of-the-art when I used SBRT for primary therapy was quite different. There were already a number of 3-year published studies on it, and it was radiobiologically modeled on HDR-brachytherapy monotherapy which already had been used for 10 years and had several long-term published studies. I'll also add some comments privately.

Decipher can be quite expensive if you have to pay out of pocket. It is valuable for patients who are on the fence about getting SRT. It tells you the risk of metastases in the next 10 years if you do nothing. If you can get insurance approval - why not?

[cyber1 in reply to Tall_Allen]

Regarding Decipher, if I get recommended by my surgeon to get the test, I will then see what my insurance will pay. I have Medicare plus Anthem Blue Cross.

[Tall_Allen in reply to cyber1]

Get pre-authorization.

[cyber1 in reply to Tall_Allen]

Just talked to my RO at the proton center. He said they don't do hypofractionation treatment.

He described the actual treatment session and he said it takes about 30 minutes because there is one cyclotron for three different treatment tables. You get radiated and then the gantry moves to the next room while you wait for it to come back. So essentially the one cyclotron continuously moves between the three treatment areas/patients. He said that is why it takes so long each day.

I was surprised by this, is that normal for pencil beam proton radiation or is that type of setup unique for this particular facility? Is that normal for any other type of radiation treatments?

I asked if they readjust the beam due to intrafractional motion between the first and second radiation treatment each day. He said they don't because the rectal balloon helps keep things in place and that because there are really 70 treatments (two per day, receiving 1.0 Gy per treatment) if one misses the target a little bit, it is not that big of a deal.

[Tall_Allen in reply to cyber1]

Yes, that's typical for protons. They book appointments to get all rooms going at the same time.

He is right that intrafractional tracking is not necessary when they are only doing 1.8 GyE (I think you meant 1.8, not 1.0) per treatment. What is the total dose they are prescribing? They don't usually hypofractionate proton therapy, especially not for salvage, although there are clinical trials. I'm surprised they still do the ass balloon for salvage - with no prostate, it is compressing and distorting the prostate bed tissues.

[cyber1 in reply to Tall_Allen]

Are protons the only ones that share the machine and make you wait between your radiation doses?

Regarding the rectal balloon, the way you worded that practice you imply it used to be a common practice but it is no longer considered standard practice because it distorts the prostate bed and therefore makes radiating that area more difficult. If that is true, then that to me is a reason to eliminate proton therapy, at least at the location in San Diego. Do you have something I can read about this?

Regarding the dosages. The total would be 70 Gy given in 35 sessions of 2.0 Gy per session. I said 1.0 Gy per fraction because each session is divided into 2 fractions. The first fraction/dose/(not sure what to call it) is given when you first lay down on the table and that fraction goes in to the prostate bed from either the left or right side of the body. Then the cyclotron goes to the other rooms and when it comes back 10 or 15 minutes later it gives another 1.0 Gy fraction by shooting the beam in through the other side of the body. So in essence you get 70 fractions of 1.0 Gy over the course of 35 days. That is what I was trying to say.

[Tall_Allen in reply to cyber1]

Yes, only protons and carbon ion (in other countries) use the shared gantry.

I did not imply that about rectal balloons. You incorrectly inferred that. What I said (repeatedly) is that salvage proton is experimental (as is salvage SBRT). I don't understand why you imagine it is standard practice. That is incorrect. I don't know how to say it more clearly.

It is 2 GyE per fraction - a delay of a few minutes doesn't change the dosimetry.

[cyber1 in reply to Tall_Allen]

Got it with the sharing of the gantry. Given this is normal practice, it seems logical that during that waiting period between the initial delivery of the radiation and when the gantry comes back for the second delivery, which is apparently 10 minutes or so, wouldn't that create intrafractional motion which seems like it is not good.

Regarding thinking that I was saying that salvage proton or SBRT is in some way a standard of care, I did not mean to say that. I know it is experimental. Sorry for the misunderstanding.

What I was talking about was only the practice of placing a balloon in the rectum. I thought what you said about the rectal balloon applied to any form of SRT. You said, "I'm surprised they still do the ass balloon for salvage - with no prostate, it is compressing and distorting the prostate bed tissues." Specifically the word 'surprised' caught my attention. I took that to mean that using a rectal balloon for SRT is no longer as common or acceptable (or fill in the blank word) as it used to be. When I read what you said about how it compresses and distorts the prostate bed tissues it made sense to me that perhaps using a balloon is not the best idea and there are other ways to not get the prostate bed to move, or at least compensate for the issue. Again tell me if I am wrong. I am going to ask Dr. Kishan if they use a rectal balloon now that I know that is something worth considering.

[fluffyfur in reply to cyber1]

A rectal balloon was never offered for my husband at one of the top cancer hospitals. Not for SRT. It's more important that your bladder is at the right level and your bowel empty prior to treatment. And again, this is a technician thing. They need to do the measurements before the machine starts up.

[cyber1 in reply to fluffyfur]

Makes sense, I think the point about compressing and distorting the prostate bed in the SRT setting is worth considering. I am going to look into this further.

[Tall_Allen in reply to cyber1]

No, Kishan certainly does not use a rectal balloon- no one using X-rays does, or at least very few.

The rectal balloon holds the prostate in place for primary proton therapy. They don't use fiducials because it creates shadows for proton therapy, and they never track intrafractional motion. It is famously used for primary proton therapy (the men who have gone through it call themselves "The Brotherhood of the Balloon.")

Because salvage proton use is experimental, they seem to have brought the balloon use over to it. I question whether that is beneficial for salvage protons because it compresses the soft tissues of the prostate bed in an unpredictable way. If there are 40 or so treatments, it may not matter much because it averages out. Perhaps the balloon is used so that during the waiting period, those tissues can't move.

When I said "I'm surprised they still do the ass balloon for salvage..." I meant "still" to refer to a carryover from primary therapy, not from an earlier use of salvage. There was no earlier use because it is experimental. Sorry for the miscommunication.

A full bladder is the most you can do to hold the prostate bed tissues in place, but they still move. That's one reason why I question whether SBRT is good for SRT.