External Beam Radiation Therapy for High Risk/Locally Advanced PCa: The Shifting Landscape

[George71]

youtube.com/watch?v=HkopU_7...(Not working as expected?)

One of the interesting points was involving RT of prostate bed vs RT of prostate bed plus whole pelvic lymph nodes in lymph node positive patients --- no benefit and no over all survival benefit to RT lymph nodes... their trial results does not support radiating lymph nodes even in lymph node positive patients.

[timotur]

Very good overview of treatment options and trials for advanced locally PCa, thanks for sharing.

[treedown]

google.com/url?sa=t&source=... here's a written brief on the video. Not sure its the same conclusion but ends with good ol more studies are needed. I read a few others citing evidence that multimedia has been shown for this risk group which I am pretty sure I am part of. And since it is how I was treated I hope this is not the case.

[GP24]

In his presentation Dr. Efstathiou discusses two situations:

5) Pelvic nodal irradiation

This is the situation when the PSA value rises but no mets can be detected.

Here he cites two studies which, as he states, show now difference when the pelvis is added to prostate bed radiation:

RTOG 94-13 updated

thelancet.com/article/S1470...

comment in:

ncbi.nlm.nih.gov/pmc/articl...

and

GETUG-1

pubmed.ncbi.nlm.nih.gov/277...

The figure he showed as „RTOG 94-13 updated“ is from an update in 2007 ncbi.nlm.nih.gov/pmc/articl...

I think it is not fair to present this figure when a later and final analysis of this trial is available which has different results. I provided a link to that above. In there the authors state:

„In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT“ (NHT=neoadjuvant hormonal therapy. PORT=prostate only radiotherapy. WPRT=whole pelvic radiotherapy.)

The GETUG-1 study, however, concludes „Pelvic nodes irradiation did not statistically improve EFS or OS“ (event-free survival (EFS), overall survival (OS))

He also mentions the RTOG 0924 study. However, as mentioned in the full text of a retrospective study reported by Sandler, the RTOG 0924 plans to provide overall survival results in 2031. So the RTOG 0924 will not provide additional information regarding overall survival until then.

europeanurology.com/article...

So there is conflicting evidence here and you cannot conclude that pelvic nodal irradiation has no effect.

6) RT in node-positive disease

In this situation he mentions several retrospective studies which show a benefit for ADT+radiation versus ADT alone. E.g. this one pubmed.ncbi.nlm.nih.gov/259... and this one jamanetwork.com/journals/ja... The last one was a retrospective analysis of a STAMPEDE control arm including 71 node positive patients only.

So for both situations there is no proof provided which therapy to select.

I would like to cite from the study by Sandler I mentioned above as it provides comments on the studies discussed:

It is possible that the benefit of WPRT was diluted in RTOG 9413 and GETUG-1 by the inclusion of patients with a very low risk of lymph node involvement [5]. Alternatively, the benefit of WPRT may be modest for patients with the highest risk of nodal involvement, as these patients are also at high risk of harboring micrometastases outside of the pelvic nodes [7].

Indeed, RTOG 0924 was designed based on a post hoc analysis of RTOG 9413, indicating that an intermediate-risk group may derive the most benefit from WPRT. Patients with Gleason grade group (GG) 5 (formerly, Gleason score [GS] 9–10) PCa are at high risk of both nodal metastases and extrapelvic micrometastases [8,9].

Recently, intensified local treatment (treatment with EBRT with a brachytherapy boost [EBRT + BT]) was shown to be associated with significantly improved clinical outcomes in this patient population when compared with dose-escalated EBRT alone in this patient population, but it is unknown how WPRT impacts these outcomes [10].

[MateoBeach in reply to GP24]

Thank you sir for your careful dissection of the evidence on this topic providing better context and depth to the consideration. Much appreciated here. As is the theory that intermediate vs. high risk stratification might be the consideration for micro-metastatic extra-pelvic disease vs PLN limited disease in the response to treatment. You are indeed a gentleman and a scholar. Or should I say doctor?

[George71]

Thanks GP24 for the input..

A couple of thoughts:

As you pointed out -- "the RTOG 0924 will not provide additional information regarding overall survival until 2031."

Based on their current evidence and conclusion -- it does not increase OS.

The only explanation for it that they can give is --- maybe a small group can benefit and is being obscured by all the others. That is pretty weak -- at best.

But assume best case scenario --- that the reason it does not currently show any benefit in OS is because a cohort in the middle (say --a full one third) would benefit and is being watered down by the other two thirds that do not benefit (the very low LN and very high LN involvement groups) . .At best, It would have to be a very modest gain for the middle group, otherwise it would have showed up as 2 or 3% in the overall 3 groups -- and when extrapolated out would be a very modest benefit of 6 or 8% for the people in the middle group. Then weigh that with all the lifetime of side effects (some being very serious -- like lifetime damage to immune system caused by WPLN RT, and much higher possibility of edema and all the complications that come with that). they will live 14 or 15 more years with all that going on QOL or they live 13 and a half or 14 and a half without (certainly) some level of side effects caused by WPLN RT. A full 15 to 20% will suffer grade 2 or 3 side effects from it.

As a side note when viewed as the only two options (RT to WPLN or not) it is pretty weak support for doing it. And when viewed in light of the other options out there (lu177 which seem to wipe out all NL mets- or immuno therapy or even just focal Spot radiation of the lymph node that shows in imaging which has an abscopal effect -(The abscopal effect occurs when radiation treatment—or another type of local therapy—not only shrinks the targeted tumor but also leads to the shrinkage of untreated tumors elsewhere in the body.)- makes RT to WPLN look less and less the way to go.

[GP24]

I recommend that you watch the presentation by Mack Roach on this subject. He discusses the studies mentioned in this thread:

urotoday.com/video-lectures...

He points out that GETUG-1 radiated a smaller area than the one defined in RTOG 94-13 and this could be the reason why RTOG 94-13 did show a benefit for radiating the lymph nodes vs GETUG-1. Also, he stresses that you should combine lymph node radiation with ADT and lymph node radiation alone is probably inadequate.

In my case lymph node radiation is not curative but palliative. Therefore, when there are alternatives, I choose the treatment which causes very few side effects. Therefore I selected SBRT spot radiation to remove my lymph node mets. Whether WPRT would have had better results I cannot tell.

There are further presentations on this subject by Alberto Bossi, Karim Fizazi and Declan Murphy:

urotoday.com/video-lectures...

[SPEEDYX in reply to GP24]

Max Roach great jazz drummer...he layed the tracks to a great presentation!!

[George71 in reply to GP24]

I think we are in general agreement -- the least damaging approach since the questionable pluses come with an unquestionable certainty of minuses