Question about biopsy results

hopeful and optimistic said:

came across this study



Role of prostate specific antigen and immediate confirmatory biopsy in predicting progression during active surveillance for low risk prostate cancer.

Adamy A, Yee DS, Matsushita K, Maschino A, Cronin A, Vickers A, Guillonneau B, Scardino PT, Eastham JA.


Source

Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. ariadamy@gmail.com


Abstract

PURPOSE:

We evaluated predictors of progression after starting active surveillance, especially the role of prostate specific antigen and immediate confirmatory prostate biopsy.

MATERIALS AND METHODS:

A total of 238 men with prostate cancer met active surveillance eligibility criteria and were analyzed for progression with time. Cox proportional hazards regression was used to evaluate predictors of progression. Progression was evaluated using 2 definitions, including no longer meeting 1) full and 2) modified criteria, excluding prostate specific antigen greater than 10 ng/ml as a criterion.

RESULTS:

Using full criteria 61 patients progressed during followup. The 2 and 5-year progression-free probability was 80% and 60%, respectively. With prostate specific antigen included in progression criteria prostate specific antigen at confirmatory biopsy (HR 1.29, 95% CI 1.14-1.46, p <0.0005) and positive confirmatory biopsy (HR 1.75, 95% CI 1.01-3.04, p = 0.047) were independent predictors of progression. Of the 61 cases 34 failed due to increased prostate specific antigen, including only 5 with subsequent progression by biopsy criteria. When prostate specific antigen was excluded from progression criteria, only 32 cases progressed, and 2 and 5-year progression-free probability was 91% and 76%, respectively. Using modified criteria as an end point positive confirmatory biopsy was the only independent predictor of progression (HR 3.16, 95% CI 1.41-7.09, p = 0.005).

CONCLUSIONS:

Active surveillance is feasible in patients with low risk prostate cancer and most patients show little evidence of progression within 5 years. There is no clear justification for treating patients in whom prostate specific antigen increases above 10 ng/ml in the absence of other indications of tumor progression. Patients considering active surveillance should undergo confirmatory biopsy to better assess the risk of progression.

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.


Comment in
Nat Rev Urol. 2011 Feb;8(2):60.


PMID: 21167529 [PubMed - indexed for MEDLINE]</p>

tarhoosier said:

Surveillance
Vasco, I understood the citation provided just above your last comment, or at least until I read you comment. What I believe the research is saying is that biopsy factors are more reliable as indicators to suspend or continue AS than is PSA. Even PSA in addition to those biopsy factors provides no significant additional validation. Biopsies can show a change in the G score and a change in the location and volume of tumor. These would be more significant factors than PSA which, as we know, is not cancer dependent.
PSA alone is not a "flag" to determine the advance of the disease in men following Active Surveillance, at least within the bounds of PSA followed in the study.

hopeful and optimistic said:

Well,
as I understand, the biopsy is key in determining where a patient stands. The gleason score shows the aggressiveness of the cancer and gives a strong indication how quickly the cancer will spread.

There is a DRE, PSA, and other markers to measure disease progression such as a PAP, PCA3, PROpsa and other markers http://ajcp.ascpjournals.org/content/supplements/120/Suppl_1/S85.full.pdf

that try to measure disease prgression, however I don't think any of them do the job. (see the last study citation, below the dotted line, at the end of this post.

In answer to your speicific question,
"Surely a biopsy is more reliable as indicator of aggressiveness as you comment, and cancer found in additional cores on a second biopsy would indicate a “different” diagnosis or a “change” in the status, but that could have been a cause of a “miss” target in the first attempt. Still I do not understand how a confirmed positive case is declared in “progression” using a biopsy for judgment"

The first biopsy can miss an aggressivre cancer, however if a second biopsy shows this, the patient will no longer be eligible for AS, and will need to seek curative treatment. This aggessive gleason may or may not be progressive from the first biopsy, but simply found on the second biopsy.

Your next question is the million dollar question, and is one that I am struggling with.

"What could be the best definition for “Indolent type of Cancer”

We know that indolent type of cancer means not likely to progress, but how do we measure this? Since I just had a third biopsy, am still being treated with Active Surveillance but am scheduled for another biopsy in two years....a very long way to go......I am very interested in determining indicators other than biopsy that will measure progression of my cancer, if any...I am doing research about this, and am grateful for any input to monitor my disease at this point.
----------------------------------------------


BMC Med Genomics. 2010 Mar 16;3:8.

Molecular sampling of prostate cancer: a dilemma for predicting disease progression.

Sboner A, Demichelis F, Calza S, Pawitan Y, Setlur SR, Hoshida Y, Perner S, Adami HO, Fall K, Mucci LA, Kantoff PW, Stampfer M, Andersson SO, Varenhorst E, Johansson JE, Gerstein MB, Golub TR, Rubin MA, Andrén O.


Source

Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA.


Abstract

BACKGROUND:

Current prostate cancer prognostic models are based on pre-treatment prostate specific antigen (PSA) levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models.

METHODS:

We analyzed a Swedish Watchful Waiting cohort with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL) method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP) samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer and men who survived more than 10 years without metastases (lethals and indolents, respectively). Several statistical and machine learning models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases.

RESULTS:

Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors.

CONCLUSIONS:

The determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses making the development of molecular biomarkers for prostate cancer progression challenging.


PMID: 20233430 [PubMed - indexed for MEDLINE] PMCID: PMC2855514 Free PMC

tarhoosier said:

Communication breakdown
This discussion is another example, if anyone needed such, that online interaction is no substitute for personal direct communication.
My original response above was to the opening post in the thread about the issue of active surveillance in the case of a man with one core positive out of 31, with less than 5% of G6 cancer. This is a little as possible to detect. The psa change(s) that the initial post author mentioned in another post elsewhere at this site was perhaps the start of some confusion. Nonetheless, there was also a post about the role of biopsy and psa in AS. Biopsy is definitive, and psa is suggestive. To go to PRIMARY treatment on suggestive rather than definitive evidence is wrong. I believe that was the conclusion of the research mentioned in the post by "hopeful". I agree with that conclusion.
After a biopsy such as that for daveirving at the top of this thread, further biopsies would be in order at some interval such as annual or every two years. The results of these biopsies may show some greater risk with G score advancing, more cores positive, a greater percentage of the cores positive or cancer noted at or near the margin of the gland. Psa would be a less important issue than biopsy factors. Psa may indicate more frequent biopsy or biopsy localized to one area or a change from transrectal to perineal to reach areas not well identified with the other type of biopsy.
I believe that prostate cancer is a progressive disease and over time will progress from G3 to G4 and eventually G5 if not addressed. I am unaware of the "rare" cases that Myers may have referred to. I think that progression is the standard for the disease. It may happen over such a long time that other health risks may impose themselves prior to the lethal stage. Such may be the case with G3+3 disease.
In regard to SECONDARY treatment I was most interested in the G score that califvader presented which was 3+3. This is an indicator of the slowest growing prostate cancer and indeed his psa was going DOWN at the time he wrote. This is what I wrote about califvader at that time:
******
Based on the limited information provided by ca.vader he has been watchfully waiting on his psa. His G6 has, as is often the case, allowed a very slow rise. His psa doubling time is impossible to determine, though his most recent psa direction was actually negative, 4.8 to 3.3. If, as I assume, his psa has been moving over some years, then this means that he has some more years to go before addressing ADT. I also assume he is on no therapy at this time. A "threat to his health" would entail symptoms or side effects serious enough to cause further treatment. I believe he is still years away from that.
It is crystal clear from his post that he is comfortable watching his psa and waiting to address the issue until some later time. Apparently his doctor(s) is (are) as well. I believe this is supported by the (few) facts he presents. I find no reason to encourage him to abandon his current course and to begin a systemic treatment.
***********

Vasco, your situation was post-treatment and not the same one as daveirving, or indeed the research subjects from "hopeful". Yours was a choice to monitor and determine when to intervene with hormone (or radiation). Biopsy was not an issue with you post treatment.
I hope this clears some confusion about what I believe about the two men discussed, califvader and daveirving, and the research presented

tarhoosier said:

I-ADT
Restarted ADT-2 December, 2010. PSADt=30Days+/-. psa at that time ~3.5. I reached 0.01 first two times on ADT.
Current psa 0.08 at seven months of treatment. I am pleased. I take 400 mg Celecoxib Am and again Pm. Bio curcumin also used, plus Vit D. D supplementation @15,000 I. U. / day. I have learned that this is necessary for me. Current D3 reading is 77 ng.
I saw my primary physician this week and I am ridiculously healthy for a 63-64 y. o. man. I use simvastatin to keep Cholesterol in "ideal" range. Cholesterol figures are satisfactory without it. There is a potential advantage for PCa with low cholesterol in serum so I continue it at low cost by generic drug.
Thanks for asking and keep posting.

VascodaGama said:

24 TYPES OF PROSTATE CANCER
IRA

Thanks for the “enlightenment”. This abstract on the “…a dilemma for predicting disease progression…” says it all. Progression cannot be based on biopsy on all situations. Probably it can only in few cases.
Looking anecdotally to the two following examples I would like to idealize the opinion from those “experts” on AS (Dr. Scardino).

Situations (1); If one guy finds himself with a Gr=3 on the first biopsy with attached PSA=4.0 and then one year later finds from the second biopsy an increase in grade of Gr=4 with attached PSA=8.0 then he may be recommended to stop AS and start a Treatment.
Situation (2); If a guy finds himself with a Gr=3 on the first biopsy with attached PSA=4.0 and then one year later finds from the second biopsy an equal grade of Gr=3 with attached PSA=8.0 then he may be recommended to CONTINUE AS.

Surely the situation (2) would alarm doctors in investigating the cause of the spike in PSA before advising on a continued AS. If the increase in PSA has been confirmed not benign related (ex. BPH, prostate manipulation the day before drawing blood; like sex, riding a bike, etc ), then the case would be judged more serious than the AS regulations.

PSA, as in the old times, is a predictive “flag” for progression but it may be not an important element/item in the INITIAL decision for recommending a patient to follow AS.
Even if the study you posted has given negative outcomes for the Molecular Sampling, I am a strong believer on the aneuploid DNA ploidy status in grading the cancers better than the visual comparison with the Gleason pattern scale. I do so because of the many varieties of prostate cancers (24 types) which may be screened with markers other than PSA. This alone reinforces the opinion that PSA can be a flag but not an element in the decision.
(http://online.wsj.com/article/SB10001424052748703279704575334982806405218.html)

I consider myself a “pudding-head” on the matter and would like to know more.

Sincerely
VGama

VascodaGama said:

Hopeful; With no regrets HAVE IT DONE
IRA

You may laugh on my little story on the subject you question, and so did some of the doctors I met along the journey of my cancer management, but I keep two samples/slides of my prostate in my survivor’s file.
Back in 2000 after diagnosis and been asked “HAVE YOU decided on a treatment?”, I went bananas and read every paper I could hold on prostate cancer. Since then I become an avid researcher and the subject that most fascinated me at the time was about the role that the Immunotherapy can have in the fight of this bandit. There were many undergoing studies on “vaccines” like therapies but these could be successful if “manufactured” to each particular case. The only way to have it done was through the information stored in the DNA of each one of us. I realised that a piece of my prostate was as important as a copy of the pathological report.

You can request a DNA test of your prostate using the core samples from the biopsy. Your doctor/hospital/clinic has the samples in their possession. How much that is helpful in your case, is evidenced in the article you posted. The usual aneuploid DNA ploidy status helps to determine probable aggressiveness. Logically one could expect Gleason patterns of 4 and 5 of being associated with aneuploidy cells. To know your P-cell type in your benign case can give you peace of mind for the interval years between biopsies. It wouldn’t surprise me if your P-cells turn to be Tetraploid (Gr=1).

For the future, the simple DNA test can be helpful in determining on a drug that cold better target the genetic variants in your chromosomes. This seems to be a “very near future” that will help many (including myself), when we read about the several practical successful studies being carried out. Provenge is one offspring product and so it is the latest test result on a vaccine posted here by MrsPJD (http://csn.cancer.org/node/220987).
It doesn’t “hurt” to have a sample of our flesh and the heredity test (DNA) of cell’s genome filed with the other common data on PCa.

In Europe much fuzze has been talked since BBC’s announcement of a cheaper DNA test. This will surely facilitate more and more developments on diagnosis, treatments and medicines for combating all types of cancer.

The best to you.
VGama