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Active surveillance, another PSA number

hopeful and opt...
Posts: 1282
Joined: Apr 2009

My PSA and free PSA numbers

1/13/2011 2.5 25
6/10/2011 3.6 18
12/16/2011 4.2 14
3/12/2012 3.9 17

Sloan Kettering:

slope log(psa) 0.39
doubling time 1.78
velocity 1.26ng/ml/yr

My complete history is available if you click my name "to about me"

I appreciate any comments/suggestions/recommendations...good or bad

thanks

Beau2
Posts: 228
Joined: Sep 2010

Looks to me like your PSA is down a bit and that your free PSA is up a bit ... unless I am missing something that sounds like good news. (I Don't know what the other numbers mean).

Looks like your diet continues to work.

Celebration time?

Wishing you the best.

VascodaGama's picture
VascodaGama
Posts: 1515
Joined: Nov 2010

Ira

You may be the best person to opinion on your case. Your knowledge on AS supers any fellow in this forum, and I think you are doing the job very well.
Against what other guys may feel when waiting for a PSA result, your anxiety increases if the PSA gets lower because you would like to be sure that cancer “exists”. Probably a positive biopsy or test would give you peace of mind.

However, I would like to offer you my sympathy in suggesting a celebration for again another confirmation that AS is the rightful choice to manage your case. And in that you are the one to be congratulated.

I never asked before if you had done a second examination on the slides of March 2009. You also never commented on the details of the path report regarding the type of cells and cancer found in the two positive cores. I recall that the Gs was 6 (3+3) standing for well differentiated, but the type of cells can also provide you with other ways in judging your case.

Not to alarm you, but dedifferentiated cells are not as easy to find in guys with your status. This type stands between well and poorly differentiated and are usually tinny compositions characterized by forming small tumours less than 5 mm in size. The theme regarding dedifferentiated cancerous cells was “hotly” discussed when in the approval of the 5-alfa reductase inhibitor drugs dutasteride (Avodart) and finasteride (Proscar).
Those are recommended to be administered as cancer prevention or to guys in AS. They are FDA approved to handle prostate hyperplasia (curing and reducing the size of the prostate), as well as drugs to impede dihydrotestosterone synthesis (DHT) in hormonal treatments.

Most of the “fuzzy” involving the discussions that these drugs “cause” (or induce) higher Gleason scores along the years in use, is exactly because dedifferentiated cells were commonly found in the folks taking the drug.
In my layman’s view on the matter I think that those studies looked “minutiously” the samples and found cancer that usually is missed in biopsies or not properly identified by pathologists. Some classify them as differentiated or even well differentiated.

What puzzles me is that your PCA3 test gave a very low value (8.3) which is consistent with well differentiated cells, proper of the type of Gleason scores 2 which classification has been abolished since 2005 (your 3 could be 2).

Just adding a note to my comments, I want to inform that I have followed biological studies addressing cells behaviour which confirmes that prostatic well differentiated stem cells may “sparkled” cancer (change from benign to malicious) if they are not fed proper “food” (androgens) for long periods of time. This may justify that male hypogonadism (guys with low levels of testosterone) are in risk of getting prostate cancer.

May I suggest you to get a T test and certify bone health (densitometry scan)!

Let me raise a glass of a good Portuguese red wine to cheer your results.

Regards

Vgama

Kongo's picture
Kongo
Posts: 1167
Joined: Mar 2010

Ira, I think those are great numbers. The fact that your PSA went up then down suggests to me that there are other things going on such as BPH or some other common thing that causes your PSA flucuation. If your cancer was growing, you could expect to see a steady rise in PSA scores over time.

The PSADT, velocity, and so forth use a model that approximates a logrythmic line (the slope) but the up and down dumbers introduce a higher element of error to the model. I suspect your PSADT is higher and your velocity lower than what your calculations indicate.

Also, the PSADT model on the MSK website assumes a post RP condition. Using this when you haven't had a RP won't give you the numbers you expect. Try using the PSADT nomogram at http://www.apogeect.com/html/pca/ and see what you get.

Best,

K

hopeful and opt...
Posts: 1282
Joined: Apr 2009

My spirts have been uplifted by each of your comments.I feel a lot better. The inputs about my case are very much appreciated.

Vasco, I am returning a toast to you with a glass of excellent red California wine.

"I never asked before if you had done a second examination on the slides of March 2009. You also never commented on the details of the path report regarding the type of cells and cancer found in the two positive cores¬¬¬¬"

3/01/09 Biopsy Report
The two cores that were positive, right side of mid prostate and right side of base were each Adenocarcinoma of prostate, acinar type, gleason score 3+3, and less than 5% of specimen.
Negative for vasucular, lymphatic, or perineural invasion
Comment:
Imunohistochemistry shows the adenocarcinoma to be positive for P504S and to be negative for 34betaE12 or p3, supporting the morphologic impression.
Second opinion, Johns Hopkins
b. small focus of adenocarcinoma of the prostate, gleason grade 3+3=6 with adjacent high grade prostaic intraepithelial neoplasia
Note: The diagnosis of carcinoma is supported by the failure of immunoperoxidase staining for P63 to demonstrate basal cells in the carcinoma.
c. small focus of adenocarcinoma of the prostate, gleason grade 3+3=6 with adjacent high grade prostatic intraepithelial neoplsia.
Note: The diagnosis of carcinoma is supported by the failure of imunoperoxidase staining for high moleculoar weight cytokeratin to demonstrate basal cells in the atypifal glands.
The diagnosis of carcinoma is supported by the failure of the immunoperodxidase staining for P63 to demonstrate basal cells in the atypical glands
…………………………………………………………………..
Aureon Laboratories (company now defunct) Molecular test…based on 3/09 slides
Supportive Features Summary:
Morhometric analysis of the prostate needle biopsy-In the sections evaluated-is consistent with a predominantly well differentiated tumor, supported by low to moderate feature values indicating spread of epithellal cells beyond lumen associated glad units, as well as by histobiometric immunofluorescence (IF) data (low to medium “minimum spanning tree” feature value, suggesting increased nuclear dispersion). Quantitative IF biomarkers results indicate a low level of expression of the androgen receptor within tumor epithelial nuclei, as well as an essentially null area of tumor cell nuclei expressing the cell cycle marker KI-67
Disease Progression score:
“low risk with a 3 percent probability of disease progression within eight years after radical prostatectomy. Additionally, the patient has a high probability 78% of having a favorable pathology.”
…………………………………………………….
The additional two biopsies that I had showed benign for all cores taken.
………………………………………………………………….
Vasco,….By the way, I spoke with a pathologist who gave a lecture, and asked if my gleason can really be of a lower aggressiveness, since the guidelines changed,i.e. be a two ; he told me no, that it’s a three….is there something that I am missing?

My T is outside the range, and is low.
(I will be asking for another T test in April by my GP)
……………………………….
Bone Scan….9-2009….I had xrays and an MRI of the lumba and pelvis for a spine condition…the doc mentioned that the bone density in my legs was dense( I do a lot of walking), and in my back moderate….I am currently walking on a daily basis, and doing some swimming and resistance training…..

Kongo…Thanks…..I went to, http://www.apogeect.com/html/pca, the site that you recommended, and for some reason I was not able to get results when I plugged the numbers in…… I will try again.

Advodart
My doc, and others suggest Advodart (the controversial drug). I am posting the results of a small study among patients on active surveillance, that shows, delayed treatments for those on Avodart versus control group.
I am strongly thinking of using this drug, any thoughts?
If I do take Avodart, I think that I should wait at least three months before using the drug, so I can determine that the PSA is stable, before any distortion resulting from the Avodart., so I can get another biopsy if necessary.

……………………………………………………
arDutasteride Slows Down Early Stage Prostate Cancer Progression
Editor's Choice
Academic Journal
Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology
Article Date: 25 Jan 2012 - 6:00 PST

Lancet has found that a common medication (dutasteride) used to treat enlargement of the prostate, may also reduce the need for treatments that pose risks of incontinenceand impotence and delay growth of early-stage prostate cancer.

Neil Fleshner, lead researcher of the investigation from Princess Margaret Hospital, Toronto, Canada, said:

"Our trial is the first study to show the benefits of use of a 5α-reductase inhibitor to reduce the need for aggressive treatment in men undergoing active surveillance for low-risk prostate cancer...delaying their time to pathological progression and initiation of primary therapy."

In the United States about 20% of males will be diagnosed with the disease, although the majority will have low-risk (low-grade, low-volume) prostate cancer. For them, it can be appropriate to stay under conservatively managed active surveillance, meaning they do not have to undergo immediate therapy in favor of regular assessment and biopsies to monitor the disease.

Dutasteride is a 5α-reductase inhibitor that works by preventing testosterone from converting to dihydrotestosterone (the male sex hormone involved in the development of prostate cancer). The drug has been approved for treating benign prostatic hyperplasia, a non-cancerous enlargement of the prostate, and has shown to decrease the volume of some prostate cancers.

302 men aged between 48 to 82 years old undergoing active surveillance for low-risk localized prostate cancer were enrolled to participate in the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM). The researchers randomly assigned the participants to two groups; one group received 0.5 mg dutasteride once daily for 3 years, while the other group received placebo for the same duration.

In order to measure time to disease progression, participants received biopsies at 18 months and 3 years. In addition, the researchers gave participants a questionnaire in order to examineanxiety associated to the disease.

The researchers found that dutasteride considerably delayed disease progression in comparison with placebo - 48% of men given placebo experienced disease progression compared with 38% of participants receiving dutasteride.

Furthermore, cancer was less likely to be detected at final biopsy for participants in the dutasteride group (36% [50 men]) compared with 23% (31) men in the placebo group. Throughout the duration of the study, those who received dutasteride also reported considerably lower cancer-related anxiety compared with men in the placebo group.

Similar side effects were observed between both groups. Drug-related adverse effects, consisting mainly of adverse sexual events or breast enlargement or tenderness, were experienced by more participants in the dutasteride group (24%) than those given placebo (15%). There were no cases of disease spread or deaths related to prostate cancer during the duration of the study.

In an associated comment, Chris Parker from the Royal Marsden National Health Service Foundation Trust, Sutton, UK wns:

"These data are consistent with the hypothesis that dutasteride reduces the volume of low-grade prostate cancers but has no effect, or even an adverse effect, on the progression of high-grade disease. Thus, although reducing overall prostate cancer detection, dutasteride could plausibly have no effect (or possibly a deleterious one) on prostate cancer mortality."

The researchers conclude:

"The benefit of dutasteride is to reduce the amount of low-grade cancer, not to reduce the risk of being diagnosed with higher-grade cancer. This reduction leads to fewer men with biopsy-detectable prostate cancer, and therefore fewer treatment interventions. Dutasteride...provides a treatment option for men with low-risk, localized disease."

Written by Grace Rattue

View drug information on dutasteride.

Copyright: Medical News Today  

VascodaGama's picture
VascodaGama
Posts: 1515
Joined: Nov 2010

IRA

I am sorry to my previous post. I should have imagined that you had all straighten out and investigated. You are in “command” of your case and hardly will get due responses to your queries from the buddies here. I am very curious on this biological matter of PCa cells and would appreciate your “hits” on my comments.

In my opinion the “well differentiated” classification of the two positive cores is totally correct confirmed in both stains. However, your type of cancer was indicated with two particularities which I thing being the reason for its “dormant” characteristics. In other words, it may not be grade 2 but it is not an aggressive grade 3. (at least in this period of testing)
This is indicated in the following path comment;
“….low to medium “minimum spanning tree” feature value, suggesting increased nuclear dispersion. Quantitative IF biomarkers results indicate a low level of expression of the androgen receptor within tumor epithelial nuclei, as well as an essentially null area of tumor cell nuclei expressing the cell cycle marker KI-67…”

The spanning tree indicates some dispersion of nucleus therefore prove of a g3. The inactivity of the AR and lack of cellular proliferation marker (KI-67) indicate no-growth to slow-growth (I say “growth” because of the pathologist’s comment 3% probability. I do not know what his basis of judgement is).

Regarding Gleason grades of 2 vz 3; I understand your doctor’s comment because that was what the pathologist saw and reported. However, pathologists nowadays tend to discriminate any dispersion as “well differentiate” and therefore PCa grade 3.

Must confusion has aroused from the “team of experts” in 2005 (International Consensus Conference of specialized urologic pathologists) who decided to group both grades into one. The opinion varied among the investigators but they all agreed that a low prognosis would not alter diagnosis (i.e. 2+3 =5=6 and 2+2=4). What I think they have missed is that the path from 2 to 3 does not occur as a continuing process (more dispersed = worse the condition) but due to genetic factors, such as the existence of proteins like the KI-67, which would be indicative of progression (they do not consider “dormant” status).
Surely, the speed of growth is higher in higher grades with verified AR (androgen receptors) activity and bio markers.

I do not know if the “2005” context was influenced by the traditional classification of “well differentiated” which incorporates the patterns; highly, intermediate and moderately differentiated (1, 2 and 3 respectively). Grades 4 and 5 are poorly differentiated. Although, we know that in the Gleason score If the secondary pattern is less than 5%, it is considered insignificant, so the grade of the dominant (the real significant) pattern would be added to itself (3 + 3 = 6). And in this we get again the controversy that in a case of grade 2 (less than 5%) plus grade 4; is not 6 but 8 (4+4).
A tertiary cell pattern can coexist (with less than 5%) and it is also considered when deciding on the aggressivity of the cancer. (e.i. Gleason grade 3 + 3 (+ 4 <5%)= 6 but judged as 7 in terms of risk).
In a case with a primary and secondary grade 3 classified as Gleason score (3 + 3)=6, if a tertiary grade of 5 coexists, it would be classified as Gleason score (3 + 5) = 8.
(can you explain that? I cannot but the 2005 team can.)

Avodart;
I agree with your waiting to get a PSA test before starting the 5-ARI drug. Moreover, the last result has shown no cancer growth (inactivity of any occult cancer). The good of Avodart will be that of “purifying” your PSA, cleaning it from any existing hyperplasia. The result of a PSA test under the influence of Avodart (in my layman’s opinion) would indicate the real PSA produced by benign and malignant cells at the prostate, seminal vesicles and urethra.
In any case, I would recommend taking it as preventive if you think that hyperplasia do not coexists from any inflamation or prostatitis (infection).

You are the Commandant of your boat and you know better than anyone else on what to believe.

I wish you more of those results.

Cheers.

VGama

mrspjd
Posts: 688
Joined: Apr 2010

Ira,

Assuming your current plan (Plan A) is to stay on pro-AS and possibly start Avodart or Finasteride (sooner or later), wondering if perhaps you’d be open to sharing your thinking re:

1) Do you have a Plan B.
2) If so, what is Plan B (tx).
3) What specific finding(s)/event(s) would trigger putting Plan B into action.
4) Considering your connection with another poster here who has posted of being “successfully” treated using SBRT as a focal tx for his very low risk PCa (and who has posted of no tx side effects), have you considered SBRT as a tx NOW? Why/Why not?
5) As previously suggested in a similar thread that you posted last year, have you given any add’l thought to obtaining a 2nd opinion re having a color doppler ultrasound (CD) image guided real time biopsy by a specialist (Bahn) next time an AS biopsy is due. I believe you’ve previously posted that you’ve had an MRImage guided biopsy by your current treating dr (who doesn’t feel the CD would be valuable—no surprise there). IMHO, obtaining a 2nd opinion from an entirely different specialist has value, even if only to confirm the opinion/findings of your current dr (a urologist, I believe).
6) Have you sought out any other/different 2nd opinions/evaluations, particularly from a different medical venue, such as the nearby Scholz/Lam PCa oncs? Why/Why not? If so, might you consider sharing that info.

With your background and extensive experience/knowledge of AS, perhaps you’d like to weigh in on the NIH’s endorsement of AS/AM and delay of tx for low risk PCa: http://www.cancer.gov/newscenter/pressreleases/2011/ProstateSurveillanceStateScience

Thx and BTW, Experienced the same system failure also re: the PSADT nomogram at http://www.apogeect.com/html/pca/ The system failed to calculate results on 3 separate attempts.

hopeful and opt...
Posts: 1282
Joined: Apr 2009

First, there is a sensitivity of 75% and specificity of 64%. What that means is that among 100 bad tumors, for example, they only can identify 75 of them. And among 100 good tumors, they identify them as bad in 36.
So in my case, here are the specific numbers that were found for the bad tumors to predict more aggressive disease, KI-67 and AR that was discussed in my previous post under Supportive Features Summary
KI-67 was 0.00.
The relative dynamic range of AR was 0.55

There are different numbers that Aueron uses to describe “the spanning tree” and Morphometric Features. The meaning of these numbers were not discussed by aureon.

Quantitative Morphometric Features from Patients H&E Sample
Relative Area Epithelial Cells outside Glands 0.28
Relative Area Epithelial Nuclei Outside gland unit 0.75
Relative Area Epithelial Nuclei Away from Lumens 0.06

Quantitative Features from patients Immunofluorenscent Sample
Average Edge Length of Epithelial Nuclei Minimum Spanning Tree 14.74

You asked, “(I say “growth” because of the pathologist’s comment 3% probability. I do not know what his basis of judgement is).”

The 3 percent probability is an Aureon proprietary score that is derived from a mathematical analysis based on multivariate analysis using the molecular information that they determine, along with information given, Gleason score, age, psa, and then compared with an eight year medium follow from five academic institutions among those patients who had a radical prostectomy and control group. The model-derived score of 3 percentindicated that I am a low risk patient.

Biopsy:
So there is a range within each Gleason grade, and hopefully mine was at the low. Now I wonder what is indicated about the the cancer when there is no ki=67 and low AR found. Is that significant to the type of prostate cancer?, the length of time since initial contraction of the cancer?, or we simply don't know and we say that it generally lowers risk of cancer spread over time.

"In any case, I would recommend taking it as preventive if you think that hyperplasia do not coexists from any inflamation or prostatitis (infection"

My urine was tested and negative for infection at the latest appoinment. To my knowledge I do not have any symptom of urinary infection.

VascodaGama's picture
VascodaGama
Posts: 1515
Joined: Nov 2010

IRA, you shouldn’t consider my comments as a guide in your case. If anything bothers you regarding your diagnosis, your team of doctors are the proper to consult and clear any doubt.

My comment on Gleason is based on resent researches regarding the biology of cells, their AR and genetic makers. I believe (as commented above) that cancer does not change its grade (Gleason) in a progressive manner without a reason. Something influences it to change. In other words a protein marker similar to KI-67 would be “provided” if a different environment would require it at the time or could possibly be due to prefixed genetic instructions (hereditary). In such a case the maker would probably be present from the very start.

There is no clue to a time frame for changing naturally but in cycles along our lives which may be called “aging”. In any case, the Gleason grade could coexist in those cycles with the same characteristics in a status of dormancy.
A Sudden lack of androgens (maybe caused by depression or even due to treatments) would imply the need in finding other means to get it. This fact could make the cells to look for androgens from other sources or it could be a trigger to cells to modify its behaviour and start manufacturing androgens by its own (intratumoral activity). A dormant status would become an active status and that a condition to change its structure and becoming not so differentiated (dedifferentiated).

Avodart will reduce the dihydrotestosterone which will alter the present environment of the cells. If enough androgens are present, intratumoral activity is not required, and in an environment lacking markers like KI-67, will probably cause no alteration to the present status.

As you know I am a believer in the intermittent modality of HT. One should be vigilant for hypogonadism for prolonged periods and should alter treatment raising the testosterone levels if required. The trigger could be any increase in lipids or an alteration on other health conditions, such as heart related, obesity (diabetes) or liver.

The best to you.
VGama

Beau2
Posts: 228
Joined: Sep 2010

Ira,
Concerning the use of Avodart, please see the article attached to the following link:

http://www.thestar.com/news/canada/article/1148616--prostate-cancer-risk-could-increase-with-use-of-hair-loss-drug-health-canada?bn=1

mrspjd
Posts: 688
Joined: Apr 2010

http://csn.cancer.org/node/226046

Especially see tarhoosier's comments.

VascodaGama's picture
VascodaGama
Posts: 1515
Joined: Nov 2010

Nice reading you back. We were missing "straight" comments.
How is PJD? Hopefully in the Zeros.

Best.
VG

hopeful and opt...
Posts: 1282
Joined: Apr 2009

Gentlemen and Lady, Thanks for the inputs on this controversial drug.

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