advice request with regards to SRT/similar post-op RP treatment

[jronne]

Any advice, opinion or insight would be greatly appreciated

Questions regarding the when(s), how and where(s) of SRT as my uPSA levels have started to rise post-op RP after 2 years.

A big issue is finding the right health insurance plan in case I need treatment in the coming year which is the issue for guys under 65 and medicare. This means I need to know a few options going forward and if the health insurance plan covers them. Hoping for no treatment in the coming year.

A friend of mine just got treated at Stanford with ADT then SRT with a post-op RP uPSA level of 0.05 after 4 years. Blind shotgun prostate bed and lymph node radiation since nothing showed on MRI imaging.

Is blind shotgun radiation preferred over waiting for higher PSA levels, positive imaging locations and targeted radiation?

My uPSA was first detectable at 17 months (with b vitamin supplements being used).

These b vitamin supplements were subsequently eliminated with uPSA being detected again at 26 months post-op RP

I am 60 years old

Ultrasensitive PSA test results - 17 months clean post op RP until positive at 22 months

Radical Prostatectomy 11/19/2015 with Gleason 3+4 at age 56

uPSA test result history

12/27/19 12/20/19 12/13/19 12/6/19 12/4/19 7/15/19

0.011 0.010 0.012 0.011 0.011 <0.006

4/3/19 11/29/18 11/16/18 9/21/18 7/16/18 4/30/18

0.008 0.007 0.009 0.007 0.007 <0.006

2/24/18 1/8/18 11/14/17 10/11/17 9/16/17 9/15/17

<0.006 0.008 <0.006 <0.006 0.009 0.010

6/5/17 3/3/17 12/1/16 8/29/16 5/4/16 1/14/16

<0.006 <0.015 <0.015 <0.015 <0.015 <0.02

my medical history is as follows

Genomic Health Decipher test score 0.22 below-average risk, 0 to 1 scale

Genomic Health Decipher test predicts metastasis risk and longevity for 5, 7 and 10 years out.

11/19/2015 Radical Prostatectomy UCSF Dr Peter Carroll da Vinci robotic surgery

Synoptic Comment for Prostate Tumors

- Type of tumor: Small acinar adenocarcinoma.

- Location of tumor: Single tumor. Left posterolateral midgland and base (1.2 cc; slides B10-12).

- Estimated volume of tumor: 1.2 cc.

- Gleason score: 3+4=7; primary pattern 3, secondary pattern 4.

- Estimated volume > Gleason pattern 3: 10%.

- Involvement of capsule: Tumor invades capsule: left posterior midgland (slides B10, B11).

- Extraprostatic extension: None.

- Margin status for tumor: No tumor at ink, but tumor into capsule is less than 0.1 mm from ink; slide B11.

- Margin status for benign prostate glands: No benign glands present at inked excision margins.

- High-grade prostatic intraepithelial neoplasia (HGPIN): Present, extensive.

- Tumor involvement of seminal vesicle: No tumor.

- Perineural infiltration: Present.

- Lymphovascular invasion: None.

- Lymph node status: Negative; total number of nodes examined: 1.

- AJCC/UICC stage: pT2aN0.

Johns Hopkins (Epstein) pathology 10/13/2015

Gleason Score: 3+4=7

Left Base

2 cores (60% + 20%) (30% Gleason pattern 4)

Kaiser pathology, 9/1/2015

STAGE: T1c

Gleason Score: 3+4=7

NUMBER CORES INVOLVED/TOTAL NUMBER CORES: 2 / 14

TOTAL CARCINOMA LENGTH: 10 mm

PSA 3.2 6/10/2014

PSA 4.8 6/8/2015

PSA 4.4 8/10/2015 (free PSA 7%)

PSA 5.0 9/28/2015 (free PSA 8%)

A) PROSTATE, RIGHT APEX, NEEDLE BIOPSY

-- ATYPICAL SMALL ACINAR PROLIFERATION

-- TOTAL SPECIMEN LENGTH, 44 MM

B) PROSTATE, RIGHT MID, NEEDLE BIOPSY

-- FOCAL HIGH GRADE PROSTATIC INTRAEPITHELIAL

NEOPLASIA

-- TOTAL SPECIMEN LENGTH, 30 MM

C) PROSTATE, RIGHT BASE, NEEDLE BIOPSY

-- FOCAL HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA

-- TOTAL SPECIMEN LENGTH, 23 MM

D) PROSTATE, LEFT APEX, NEEDLE BIOPSY

-- BENIGN PROSTATIC GLANDS AND STROMA, 43 MM

E) PROSTATE, LEFT MID, NEEDLE BIOPSY

-- BENIGN PROSTATIC GLANDS AND STROMA, 22 MM

F) PROSTATE, LEFT BASE

ADENOCARCINOMA, GLEASON GRADE 3+4 = 7

ADENOCARCINOMA INVOLVES 2 OF 2 CORES AND 10 MM OF 30 MM

The first involved core from the left base contains 3 mm of Gleason grade 3+3=6 adenocarcinoma and the adenocarcinoma is located 6 mm from the presumed peripheral edge (see note).

The total core length is 17 mm.

The second involved core from the left base contains 7 mm of adenocarcinoma. Greater than 6 mm of the adenocarcinoma is Gleason grade 3 and less than 1 mm is Gleason grade 4. The Gleason grade 4

adenocarcinoma is located approximately 2 mm from the presumed peripheral edge (see note).

The total core length is 13 mm.

NO PERINEURAL INVASION IDENTIFIED

[Tall_Allen]

Maybe I missed it - why exactly do you think you need SRT? All the uPSAs you wrote were under 0.03 and what kind of doctor do you have that would do PSA tests that frequently? Suggest you find a different doctor.

[jronne in reply to Tall_Allen]

thx, going to back off on the testing rate, just trying to eliminate noise, anyways for now I am 0.011 which makes me wonder if the < 0.006 on 7/14/19 was a lab error as more than doubling in 5 months is concerning, I realize there are margins of error for testing along with natural variability in micro amounts of PSA, I just do not know how to quantify them

[Tall_Allen in reply to jronne]

No that is not "concerning" - it is very low. Doubling time is not a valid measure for such low PSAs.

[jronne in reply to Tall_Allen]

hey, I appreciate your attention and knowledge, I am a CalTech grad with small dabbling in genetics and biochemistry. was a physical chemistry major with lots of applied math so I understand stats and standard deviations. the PSA test results are pretty well understood with guys with prostates and somewhat understood for post-RP guys with BCR at 0.1 and above.

not much is published in terms of fluctuations of small values of uPSA over longer periods that I can find. I wonder why there is an apparent hole in the research data as these small uPSA values either are meaningful, only occasionally meaningful or useless probably largely dependent on the individual in question. i made my living most recently as a machine learning bigData software guy in silicon valley and I would love to see uPSA trends coupled with Decipher scores and pathology. In my case, my uPSA crossed 0.006 to 0.008 at 25 months post-RP and I have a decipher score of .21 so I wonder what are my odds of post RP BCR is in 5 years, 10 years, etc ...

I realize that this data is by and large hard to come by as it is forward-looking and the uPSA test at 0.006 is new

the uPSA test at 0.006 sensitivity which was initially great news for me as I was less than 0.006 for one cycle 18 months post RP. if the test remained at 0.015 sensitivity I would be fat, dumb and happy for the last 28 months. instead, my uPSA has been measurable far more than not. uPSA also gets impacted by biotin and supplements which launched this confusing journey at 21 months post RP with 0.009 uPSA and then < 0.006 2 weeks later when I cut out biotin.

I do not understand the utility and value of the uPSA test that has a 0.003 sensitivity as it probably creates even more uncertainty than definitive results.

[Tall_Allen in reply to jronne]

You are right that PSADT has only been defined for PSAs above 0.1 - it is invalid for lower PSAs. uPSAs below 0.03 have no prognostic value.

pcnrv.blogspot.com/2016/08/...

[Hidden]

In a nutshell, I wouldn't worry yet.

I did some number crunching with your PSA values, excluding all these that are less than "<" , as they are ill defined for any time trending calculation.

I noticed a couple of things:

1) You are probably having tests with more than one lab at close times.

Most people will tell you that this is a bad practice.

I belong to the minority that will commend you for this, as long as the double-or-repeat tests are not interleaved in longer time, i.e. take the two tests close in time.

2) Up until ~30 months post RP your PSA had a descending trend.

According to current practice for PSADT this period shall be ignored.

Now, TA will tell you that there is no PSADT for values under 0.1.

This is also advertised in the MSKCC online calculator.

For this reason I will use the term "trending".

Taking into account your PSA values from July 2018 onward, there is a very swallow upwards trending.

Estimated values for future PSA, as a function of time after RP are:

Time (months); Mean PSA; 95% Confidence interval (from -to)

60 ; 0.015 ; (0.005-0.046)

70 ; 0.020 ; (0.006-0.067)

80 ; 0.026 ; (0.007-0.099)

Consequently, if you elect to start an early salvage RT at ~0.05, you have more than one year in front of you.

If you push it a bit further to ~ 0.1, which complying with currently running trials is not considered, by any means, as "late", you have two years and counting.

Have some nice Christmas and New Year. This sums it all!

[jronne in reply to Hidden]

thx for the detailed response as it helps me quantify what I might be facing.

your words and efforts are not lost on me even though I am still learning

I only use LabCorp and always use the same lab. the close retests are a somewhat lame attempt to try to reduce noise. hopefully the PSADT calculations account for these nearby datapoints essentially coalescing them into a range.

the first question is that in your opinion will my PSA likely continue to rise making the need for salvage RT just a matter of when not if ? I would like to know the odds of my PSA plateauing or is this just wishful thinking?

if I opted for very early salvage RT at 0.05 what would be the expected time window and the median time from now ?

what is my doubling time according to the calculator? is this listed on the output?

does a longer doubling time reduce the need for very early salvage RT as the risk is lower?

I would like to know which calculator you used and the caveats of adding data points as some are ignored correct ?

Jeff

[Hidden in reply to jronne]

Hi Jeff,

It should be me, thanking you for validating my past post on the precision of the PSA test.

healthunlocked.com/prostate...

Your averaging method is more sophisticated than lame.

During 11/2018 you had two tests of 0.09 and 0.07, spaced two weeks apart.

This month, three tests of 0.011, 0.012 and 0.010, also within two weeks.

In the same post I was also expressing my opinion that the advice to use the same lab is worthless. Your data series proves it. Furthermore, the idea underlying this advice is to have a standardized test. You mention that you used the same lab.

Yet, your undetectable values start with <0.015 and than at some point in time change to <0.006 indicating an important change in the test. We will never know how many, less obvious, changes had occurred during the entire time span.

Regarding your question pertaining to your eventual need for an eSRT, my true and honest opinion is: "I don't have the faintest idea".

I know this will not satisfy you, so I will add some topping as food for thought.

Pro argument:

This will answer to you regarding my methodology aswell.

I use Excel linear and exponential regression of the PSA counts vs time.

Your data, starting from July 2018, show a slightly better fit for exponential vs linear regression (R^2 = 0.8324 vs 0.8268 -higher is more binding). Elementary statistics say that anything above 0.75 is an adequate proof of an underlying regression. Also, the proliferation mechanism of cancerous cells (by multiplicative dividing, like in nuclear physics) tracks better to the exponential pattern. Consequently, this gives some very slight precedence to cancerous cell PSA production, because there is a small number or other organs * that can produce tiny quantities of benign PSA. My understanding is that this is the reason behind the MSKCC cut-off of 0.1 for PSADT, i.e. make certain that measured PSA is originating from cancerous cells and not from somewhere else. All in all, this is nothing but a very slim indication.

Against arguments:

Your initial 30 months of PSA descend. Was this PSA from cancerous cells that progressively went dormant? If so, can-or-will they do it again? Or, is it benign PSA that has its ups and downs. Only time will show.

Lastly, and for the above mentioned reasons, I will not gamble stating a PSADT time.

I can only speculate that at your current pace your 2020 Christmas tests will be somewhere around 0.016.

So, relax and keep your "lame" noise reduction engine on.

It's the best you can do.

PS (*):

"......neither PSA nor hK2 transcripts were found in neuronal tissues, whereas high levels of both transcripts were detected in the trachea, thyroid and mammary and salivary glands,and very low levels were found in pancreas. "

From: "Expression of Prostate-Specific Antigen (PSA) and Human Glandular Kallikrein 2(hK2) in Ileum and Other Extraprostatic Tissues."

onlinelibrary.wiley.com/doi...

[jronne in reply to Hidden]

going to get tested again in week or two

curious as to the plot if these two biotin supplement data points are absent

9/16/17 0.009

9/15/17

0.010

the summarized up and down is as follows

any comments or insights welcome

the lab changed tests from 0.020 sensitivity to 0.015 sensitivity to 0.006 sensitivity

this was at first a relief as

RP on 11/15

1/14/16 <0.02

5/4/16 < 0.015

6/5/17 < 0.006

as I was <0.006 18 months post RP in maybe in the clear forever

then stress

9/16/17 0.009

9/15/17

0.010

then relief cutting out the biotin B7 supplements

10/11/17 <0.006

then stress

1/8/18 0.008

realizing that I was going to have measurable uPSA perhaps indefinitely that could rise

then relief

7/15/19 <0.006

realizing that my uPSA was flat or very slow rising over 18 months

then stress

12/27/19 12/20/19 12/13/19 12/6/19 12/4/19

0.011 0.010 0.012 0.011 0.011

realizing my uPSA had more than doubled in less than 5 months

[Hidden in reply to jronne]

Your assessment is unsubstantiated.

You are stressing the numbers beyond their validity point.

Look at it this way:

1) The lab states a minimum detectable value of 0.006.

This translates to an inherent measurement error of +/- 0.0025 (anything between 0.000 to 0.005 will be reported under a unique value, that of <0.006).

2) You have five (5) measurements within 23 days in December 2019, averaging to 0.011 with a standard deviation (σ) of 0.0007. Assuming normal distribution of all measurement errors, +/- 3 σ are accounted for 99.7% of cases.

In other words, with 99.7% certainty your recent PSA is somewhere from 0.009 to 0.013 with most probable value of 0.011. Alternatively, with 95% (+/- 2σ) 0.0095-0.0125 (notice my rounding of the numbers).

Conclusion:

With your current numbers any attempt to calculate a doubling time is conceptually flawed. Will re-evaluate after your next test. Don't rush it though.

[j-o-h-n in reply to Hidden]

Do you have time to do my 2019 tax return? You guys make me feel like a doorknob...

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/23/2019 6:37 PM EST

[LowT]

What was the size of your prostate gland?

[jronne in reply to LowT]

Estimated volume of tumor: 1.2 cc.

that is all I have