To SRT or Not to SRT? Ignore 24-gene PORTOS Test?

John_TX said...
As far as the cured vs. remission dialog, my thought is if I don't expire from prostate cancer, then I'm cured.

John, you may have bone mets and die from a heart attack. You were not cured but you did not die from PCa.

Tomson,

I tried to point out treatments which should result in less SE than IMRT radiation. My understanding was that you worried about the SE of the radiation. I did not want to say these treatments are superior to IMRT. Yes, brachytherapy is used when you have a recurrence after IMRT and not after RPE. I forgot about that.

George

Post Edited (George_) : 11/23/2016 2:00:58 PM (GMT-7)

Jerry, Thanks for the words of encouragement. I would love to have your experience with positive SRT although I am aware that nothing is guaranteed. In the spirit of due diligence, I am still thinking of getting a remote second opinion from Johns Hopkins. If I decide to go ahead with radiation despite my unpromising score on the new PORTOS genomic test, I don't want to look back and second guess myself, so it may help to see what another excellent radiation oncologist think of my odds of benefiting from SRT. Given the quality of UCSF's operation, I am not interested in going anywhere else for treatment. Thanks for sharing your story, Tomson

George,

Thanks for the citation. I couldn't get past the pay wall to read the new paper, but the conclusion that tertiary Gleason pattern 5 is predictive of significantly worse outcomes seems well established.

In 2005, the International Society of Urologic Pathology consensus conference recommended that men with biopsy Gleason score 3 + 4 or 4 + 3 prostate cancer and tertiary pattern 5 should have their cancer classified as Gleason score 8 or 9, respectively.

I'm not sure what they were relying on in 2005, but since then, many articles have supported their recommendation.

Tertiary Gleason Pattern 5 is Powerful Predictor of Biochemical Relapse in Patients With Gleason Score 7 Prostatic Adenocarcinoma is a 2006 article in the Journal of Urology that concluded, "Regardless of whether the primary Gleason pattern is a 3 or 4, a tertiary Gleason pattern 5 is the strongest predictor of a worse outcome in patients with Gleason [score] 7 prostatic adenocarcinoma."

PSA Failure Following Definitive Treatment of Prostate Cancer Having Biopsy Gleason Score 7 With Tertiary Grade 5 is a 2007 communication from JAMA that concluded,"men with prostate cancer having biopsy Gleason score 7 and tertiary grade 5 had a higher risk of PSA-failure when compared with men with Gleason score 7 without tertiary grade 5 and had comparable risk with men with Gleason score 8 to 10."

Skipping a number of years ahead (and a number of other studies showing the same results), a 2015 article in the journal Cancer did not mince words in its title, Gleason Pattern 5 Is the Strongest Pathologic Predictor of Recurrence, Metastasis, and Prostate Cancer-Specific Death in Patients Receiving Salvage Radiation Therapy Following Radical Prostatectomy". This article is not hidden behind a pay wall so those who are interested can take a look at the footnotes for links to other research that has illuminated the significance of GP5. The authors concluded that "restratification of the Gleason scoring system with the presence of GP5 defining the highest-risk group was a better predictor of patient outcomes than the traditional Gleason scoring system. Clearly, patients with GP5 do not have same clinical prognosis as patients with GS8(4+4), and thus the two should not be considered as one entity when stratifying patient risk by Gleason score."

Given that they were certainly aware of this research, I was not happy that, at my post-op conference, I had to raise the issue of the tertiary GP5 finding in my pathology report. Of course, I didn't know then what I know now as I was more relishing my first post-surgery than worrying about a biochemical recurrence that might never come. I'm trying to factor my tertiary GP5 into decision-making about SRT. The 2015 Cancer article suggests, "Whereas patients with GP5 have a higher likelihood of not responding to SRT than those without GP5, those with localized GP5 recurrences constitute the group of patients for whom SRT may have the potential to provide the greatest benefit." A dark cloud with a silver lining?

Tomson

Tomson -

Wonder if it wouldn't be worth a 3 month shot of Lupron now while you are in the process of making the SRT decision? That would buy you a couple of months before any SRT would normally begin. Said another way, if you are not going to do SRT the Lupron would be the next step anyway. (I think)

Hate to see you wait if you are going to move ahead. You would never know if SRT fails if it was because of the T-5 cells or if you just didn't start treatment soon enough.

As I have said before, really a very tough call.

Gemlin,

You may be right that there is no consensus on TGP5 as an independent predictor of biochemical recurrence after prostatectomy; however, my post only scratched the surface in citing studies touting its clinicial signficance. In addition to the 2015 Cancer article I cited, another article was published this month, The prognostic role of tertiary Gleason pattern 5 in a contemporary grading system for prostate cancer, concludes that under the new one-through-five grading system that has been adopted by the World Health Organization, the biochemical recurrence rate for Gleason score 7 patients was comparable to the next higher group for those with GP5. In the 2016 article Impact of Gleason pattern 5 including tertiary pattern 5 on outcomes of salvage treatment for biochemical recurrence in pT2-3N0M0 prostate cancer, the authors conclude "The presence of GP5 is an independent predictor of poor prognosis in patients with pT2-3N0M0 PC undergoing salvage treatment for BCR after radical prostatectomy. GP5 may thus be a more useful marker than conventional Gleason scoring in this setting."

Personally, I was diagnosed as a Gleason 7(3+4) with an 88% chance of BCR-free survival at 5 years. I am rapidly approaching biochemical recurrence in less than 2 years after prostatectomy if the trendline continues, so the studies of BCR are not gonna help me although the presence of some very disordered cells may have something to do with my turning up on the early BCR list. Otherwise, my pathology report was fairly favorable. Understanding what TG5 might mean in relation to future decisions about therapy could be useful. I appreciate your sending the link to the Japanese study from 2011. It does seem to run counter to most of the studies of GP5 and it would be interesting to find an explanation for that seeming discrepancy. I am still having a hard time grasping some of what I'm reading and using the terminology correctly when I write.

Best,

Tomson

An update for those who are interested:

Unless something changes my mind, I'll be starting a course of 39 fractions 1.8 Gy (70.2 Gy total) at UCSF in early January and I will not be combining it with ADT. The hope is that my PCa is still localized and radio-sensitive. I understand that my odds are not great and I will have to live with the fact that my slight recovery from nearly total ED may be over.

Despite my low PORTOS score, my radiation oncologist clarified in followup communications that he does, in fact, recommend SRT--something that wasn't completely clear in our face-to-face encounter. I sent my records to Johns Hopkins for a medical second opinion (MSO). Just unwrapped that today and found that it agrees with my RO's recommendation of SRT. The UCSF doc is not encouraging me to combine ADT with the SRT, because (as I think I explained earlier in this thread) he believes I am not likely to derive enough additional benefit from the concurrent ADT to outweigh the risk of the side effects. JH just says, given my overall excellent health and prostate pathology, they would recommend "consideration" of ADT during RT. I am inclined to trust my RO's advice on this although I confess that my fear of ADT plays a role.

For the science buffs, the PORTOS score is explained by Allen in depth but in (mostly?) lay terms here. The PORTOS score is an exciting new development (although it brought unwelcome news in my case). However, because PORTOS is in the subject line and others may happen upon this thread as PORTOS scores become more widely reported, I will pass on a few caveats. The study published in Lancet Oncology regarding this genomic signature has some limitations. Among them, the researchers were unable to capture the time between prostatectomy and salvage radiation, PSA level when initiating SRT, PSA doubling time, post-surgery PSA nadir, and positive margin status (or Gleason grade at the margin). In addition, it has not been validated by other researchers yet. If I were to take it as a final word, I would not be doing SRT.

One thing that differed slightly in my RO's analysis and JH's is that JH identified my rapid PSA doubling time (about 3.5 months) as a factor weighing in favor of salvage treatment. My RO did not even think that a meaningful doubling time could be calculated when my PSA was still so low. However, my February to December PSA scores followed a very regular doubling pattern (linear on a logarithmic scale). No "bouncing around."

In another thread, Tall Allen mentioned that Dr. King is already routinely delivering 72 Gy (not 70.2 Gy) and MSK may be doing so for SRT as indications are that dosage escalation may correlate with greater chance of cure. Can anyone confirm this about MSK? I'm planning to forward Dr. King's study to my RO and would like to pass on accurate info about other ROs who have expanded the envelope.

Tomson

Tomson,

This was the MSK study - a patient told me he got a 72 Gy SRT dose there recently:
www.redjournal.org/article/S0360-3016(11)03485-7/abstract

The U of Torina also studied a 72 Gy dose:
link.springer.com/article/10.1007%2Fs00432-014-1673-8

The study of the 76 Gy dose was at Ghent University (and updated):
/www.ncbi.nlm.nih.gov/pubmed/18771809
/www.ncbi.nlm.nih.gov/pubmed/21514039

I'm sure UCSF has top notch equipment and they also use fiducials for SRT, which probably improves safety. It would be nice to wait for 10 years for the study data, but you don't have that luxury, so it's gotta be a judgement call.