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Scans and Imaging - how do doctors handle possibility of false negatives or false positives ?

hesno
Posts: 11
Joined: Jul 2016

I realize this might be obvious to some but its just not clear to me; I have not gone thru this yet but need to very soon.

I am asking at a very high level - my questions are about how oncologists or other doctors handle the possibility of false positive or false negative results of an image scan (and perhaps how they make sure some positive report item is diagnosed correctly in itself)

I have read in general about common situations of false positives or false negatives, where treatment started that should not have or treatment was not started that should have, as a result of these false results.

And am asking about someone who has had recurrence of the pca after treatment;  not asking about initial diagnosis or treatment.  (my treatment was imrt with 6 months adt, there was no surgery done but am asking at a high level and realize my questions can apply to anyone who needs to get scans) 

Am not asking about any specific imaging  type but assuming CT and  bone scans (but not referring to acetate or choline ones since I wil not be able to get those though realize for my questions it does not matter, since am not asking about any certain psa value at time of scan)

My question:

 Do doctors just accept the reported  scan results and then, if they feel treatment is needed  based on those results and other data, (or if treatment has been going on already)  do they just start or stop or modify the treatment based on those scan results (plus other data they have like psa, psadt, etc)  ?

OR

Do they make no treatment decisions based just on that scan itself and instead do the scan again after some time. to make sure that the first scan was not a false negative or positive - that is, assumption here is that the 2nd scan would confirm or not the first scan ?

(yet I realize there could be false negatives or positives in 2nd scan also or not as well, and thus how would one know the 2nd one was any more accurate than the first one, and also, that things could have changed in between the first scan where there could be things that showed in second scan that did not show in first (for example that psa was higher at time of 2nd scan and thus indirectly something showed then that did not show before)

OR

Do they take some other actions related to interpreting the scans and using that data as part of their decision making on how to proceed ?

 

I realize that perhaps my questions might not be logical if a Dr. cannot know at time of scan results if a given scan is true positive or true negative or false positive or false negative ?

PS -  I guess the topic of  possibility of mis-diagnosis of a given scan result (whether it was true positive or false positive/negative, is another question in this area - how they make sure its really say a metastases to bone or soft tissue areas vs some other thing not related to the pca which would not treatment.

 

Anyway, thanks for your patience with reading my questions.

hopeful and opt...
Posts: 2218
Joined: Apr 2009

To be honest I have a problem in understanding exactly what your question is , another poster may be able to answer 

I wonder if your question is about your situation. If so, please give the specifics about your case and the results of the tests that were done. This can illicit practical responses

Best 

Old Salt
Posts: 720
Joined: Aug 2014

Of course they exist. But I think that the doctors go with the results as they are presented in the radiology (or other) reports and may or may not consider the likelihood of false negatives or false positives. For instance, in my case (Gleason 9) I had a scan to look for metastasis. Lucky for me, the radiologist reported (in a careful way) that she found no evidence for metastases. Note that the report didn't state that there were no metastases! Only that, with the technology that was used, there was no evidence. My subsequent treatment by the radiation oncologist was based on that report. In this case, it didn't make sense (IMHO) to believe that the scan result was a false negative.

On the other hand, had the scan indicated evidence for metastases, an entirely different therapy would have been appropriate (probably chemo with taxotere). Assuming that the scan result would be due to a false positive, would have been 'ill-advised', IMHO.

More in general, if a doctor is unsure about a result, he/she would consider follow-up, or repeat, tests and go from there.

hesno
Posts: 11
Joined: Jul 2016

 

Old Salt, Thanks for your reply and your clear example citing your own experience in context of my questions as well as the last sentence of the post related to the general situation. All of this is very helpful for me and really helps me get a better idea of this topic. Thanks again.

Max Former Hodgkins Stage 3's picture
Max Former Hodg...
Posts: 3188
Joined: May 2012

I completely agree with Old Salt's take.  Most results, unless they contain odd or contradictory data, are accepted by the doctor at face value.  Some people fall into an endless fright, continuously worrying about the tests themselves. This is unnecesssary and counterproductive. While a few horror stories have been told here regarding tests,  they are rare.

Regarding the prostate:  false negatives are much, much more common than false positives. 

max

hesno
Posts: 11
Joined: Jul 2016

Max,

As to what you mentioned about false negatives being more common than false positives as regards pca, (am referring to scans/imaging related to hard or soft metastases rather than in prostate itself)

is that because at some given time imaging is done,that the growths are not yet visible but still there

or is it something else that happens related to pca itself that cause more false negatives than false positives ?

(I have read that often the imaging might not show anything if psa is below certain values, which I think is really saying that psa can be a measure of how fast the cells are multiplying in this case, rather than saying that psa itself is causing the situation and thus that if psa is higher there could be more of a chance that the growths are larger and thus potentially more visible by a given type of imaging. I've read also that this is not always the case, that imaging can show things if psa is lower as well)

Max Former Hodgkins Stage 3's picture
Max Former Hodg...
Posts: 3188
Joined: May 2012

Vasco answered your question regarding false negatives in great technical detail. 

I came to prostate cancer after having had advanced lymphoma, and I must say that PCa sadly is a disease that suffers from poor available imaging, compared to other cancers. The tumors are often too tiny for CTs or PET scans to be of any value.  While the newer MRIs are an advance, PCa imaging still lags.

The biospy is the gold, and really only, standard for making an informed decision.  The Gleason and PSA vector are fundamental.  Imaging, various blood tests, the DRE, all of these together are how we proceed.   It is an imperfect system, but still in most cases these are reasonable and failry clear guideposts.

.

VascodaGama's picture
VascodaGama
Posts: 2933
Joined: Nov 2010

The truth is that we have no image equipment able of specifically detect cancerous tissues. X-ray, Ultrasound, CT, MRI, PET, etc, may show deformations/proturberances or image uptaking values (SUVs) whose results are then compared with previous images/exams/standard values and used to judge the condition. All is based on past experiences and physicians decide accordingly. Obtained data is the best available and used together with other related information (DRE, PSA, PAP, Symptoms, Health issues, Pathologist reports, etc) to diagnose a condition.

Each piece of data is therefore important in the judgment and should be the best one can obtain. Surely, an MRI is more specific that a CT; or a 3T MRI has higher resolution in image "formation" than a 1.5T MRI where size is crucial; or a Flurocholine (FCH-18) contrast agent provides better SUV than a Fludeoxyglucose (FDG-18) contrast agent in PET scans where PSA is crucial; or a molecular image using zirconium-89 radiotracer that has more affinity to PSMA (prostate specific membrane antigen) than 68 Gallium to create “hot spots” of PSMA overexpression; or that PET exams leads to lesser false negatives not only in the primary tumor, but also at lymph nodes and bone metastases, permitting wider diagnosis of patient status; or, etc. etc.

For those that can afford I recommend to look for the best exam at their reach. That could be via insurance, national health care programs or at his own expenses. The facilities, team of physicians and operators should be the highly experienced at each specialty.

One should have in mind that each case is different requiring different approaches to tackle the issue in each particular case. Tumor formation may differ into one solo colony or in spread micrometastases producing large volumes of PSA serum but with smaller sizes. There are 25 types of PCa some producing lesser PSA therefore with better possibility in detection via a PSMA exam. In the end, our choices are the best and we should never regret past decisions.

We may help you in understanding fats if you provide specific details about the reason of your inquire.

Best wishes,

VGama

hesno
Posts: 11
Joined: Jul 2016

VGama,

Thanks for your detailed reply.  And thanks for clarifying that doctors use other data than just the exam results; I know it might seem obvious but not to me so far, since am just entering this phase.

As to my own details, certainly I will provide them as time goes on.  At this point, I am getting close to or at the 2.0+nadir(which in my case is 2.0) that have been told is one way to view recurrence after IMRT only,

and that scans would be next steps.  Thus in reading about scans/imaging, I read about false positives and negatives and thats what led to my questions in this post.

I still need to pick an oncologist, have seen 2 so far for consult only, and trying to evaluate whats most important to me in dr relationship as to ongoing.

Due to caregiver responsibilities I have, will not be able to travel overseas or even to mayo or AZ for the choline or acetate scans, but can get the F18 sodium flouride ones here and also 3T MRI besides usual CT scans.

My next goal in understanding basic things related to recurrence is to try to understand pros/cons of waiting to start treatment in order for psa to be high enough so that perhaps  scans might better find things (assuming initial scans are negative) VS starting treatment with ADT based just on psa or psadt (again assuming initial scans are negative)

(which assuming psa is reduced, could make it less possible scans would find anything going forward)

(though as you mention, some types of pca produce lesser psa but still can be growths but just not seen by exams)

I've read that some men want to find out where the growths are  and thus let psa get higher, and I think its because if there are a few, then spot radiation might be done, but I'm not sure if this is correct and am in general unclear on the whole concept.

Anyway, thats where I'm at right now, and I thank you again for your comments.

VascodaGama's picture
VascodaGama
Posts: 2933
Joined: Nov 2010

Hesno,

I believe you are referring to the oligometastatic cancer treatment; meaning a fewer numbers of cancer spots that can successfully be radiated and still provide cure to a RT previously treated patient.

The most recommended physicians in this sort of treatment, because of their established experience since 2011, is the /Dattoli/Myers team. Firstly they would subject the patient to a USPIO MRI (feraheme contrast agent) exam to identify the oligometastases and then would recommend a protocol involving drugs plus radiation. Myers is a famous oncologist specialist in prostate cancer. Dattoli is a radiologist and the MRI exams (metastases) would be interpreted by Dr. Solace.
In this forum there are some survivors who did this treatment, but they have reported that the USPIO exam did not identify those spots (evident false negatives).

My opinion is that Feraheme (iron) has limits in providing images of metastases when the cancer is relatively small in size (measured through the PSA). However, better contrast agents have been found and now we have more probabilities in identifying and locating metastases of 1mm in size (PSA>2.5). The best contrasts are choline based, F18 (FCH) or C11 which are practical and can do the job well using a PET/MRI machine. This exam is practiced at several locations in the USA. Maybe you can find a facility near to your place.

Still better exams exist not dependent of the size of the cancer but identifying the bandit via its PSMA (prostate specific membrane antigen) using PET with a proper radiotracer, but this is still considered investigational in the USA so that one should be involved in a trial. Please read the comments from a survivor in this forum involved in this trial here;

https://csn.cancer.org/node/303009

You can read about oligometastatic therapy in these links. Note that one is from the ASCO annual meeting of Jun 5 2016;

https://am.asco.org/treating-oligometastatic-disease-prostate-cancer
https://ro-journal.biomedcentral.com/articles/10.1186/s13014-014-0258-7
http://www.birminghamprostateclinic.co.uk/prostate/treatments/oligometastatic-prostate-cancer/

I assume that you have seen your PSA increase since IMRT therapy so that you are thinking of recurrence. However, please note that RT patients can experience a surge of PSA followed by a decline due to a phenomenal known as “bounce PSA”. Such increase may not signify recurrence. The bounce occurs in RT treatments because of inflammation of prostatic cells (benign and cancerous), and it can last years at high levels before it declines again to a “real” nadir. RT may not “kill” the whole gland (vz surgery that dissects it whole) so that these patients will have always a PSA value.

If in your shoes I would wait longer to certify if bounce is the culprit of the event.

Best wishes,

VGama

 

bob33462
Posts: 78
Joined: Feb 2016

There are 68 Ga PSMA trials going in San Francisco and Houston. This scan has showm superior to any other scan avaialable. Of courese, you can travel to Germany or Austraila to have it, where they have had the scan available for years.

This PSMA scan will be a treatment changer!

Bobby Mac

hesno
Posts: 11
Joined: Jul 2016

VGama,

Thanks for the info on oligometastatic pca - I was not familiar with that.  Seems the more I read
 the less I know and often seem to be missing key concepts.

As to the other scans than nacl f18 or older bone scan - the acetate and choline are done just at one location each in US - neither covered by medicare, or at least the tracer agents are not.

As bob33462 states above, there are trials of 68 ga psma; the one at ucsf is for a pet/ct or pet/mri (they have such a machine).  The isotope is not covered by medicare, would be $1600.   Its not clear yet if medicare would cover the pet/ct or pet/mri itself; their rules for clinical trials are more strict than I had imagined.

Am not sure if having that would preclude one from having other scans in a short timeframe if needed as to medicare rules.

As to could my psa rise be part of a long running bounce after imrt ?  Certainly it would be my fondest dream and  a very, very happy situation.  But alas, I don't think its so. imrt treatment was 5 years ago, with 6 mos adt before and during treatment.  after treatment psa was :

01-2011 - 08/2011 - < 0.1 - while on 6 mo adt (which was before and during imrt (8 mos)
09/2011 – 12/2011 – 0.1 and one 0.2 (for 3 months)
01/2012 - 07/2012 - < 0.1 (one time it was 0.1) (for 7 months)
08/2012 - 10/2012 - 0.3, 0.2, 0.2 - perhaps this was a bounce ? (for 3 months)
09/2012 – 07/2013 - 0.1 (for 9 months)
09/2013 - 0.2
09/2013 - 02/2014 - 0.2 (for 5 months)
03/2014 - 09/2014 - alternated each month between 0.2 and 0.3 – (for 6 months)
09/2014 - 1/2015 - 0.3 (for 5 months)
2/25/2015 0.4
4/14/2015 0.5
5/15/2015 0.5
6/22/2015 0.6
7/26/2015 0.6
9/08/2015 0.7
10/23/2015 0.9
12/09/2015 1.0
01/20/2016 1.2
02/29/2016 1.5
03/23/2016 1.6
05/05/2016 1.6
05/27/2016 1.8
07/07/2016 - waiting for results

===> the 08-10/2012 went up to 0.2 and 0.3 then back down to 0.1, so assumed that was the bounce and happened about a year after treatment (it was a strange time, my thyroid and some other lab values went haywire during that time as well; the thyroid did self resolve that time.

- the psadt has been 5 months more or less in any case and I bet the latest results will be at 2.0 if not higher which is what is driving my research now, looking to find a doctor, etc.

Thanks again for your comments

 

 

VascodaGama's picture
VascodaGama
Posts: 2933
Joined: Nov 2010

Hesno,

You are welcome. I like to help the many comrades but please note that I am not a doctor. I am a survivor like you looking for a chance in cure via the oligometastatic therapy.
After reading your PSA histology, I think you are correct in predicting recurrence. You are doing it well in procuring already an oncologist and salvage treatment. In any case you shouldn't rush. The doubling since 2014 (post nadir) is not short. The PSADT is above 14 months (not 5 as you comment) which is reasonable for a recurrence case after radiation. Worrisome cases indicating aggressivity are doublings lower than 9 months.

I wonder what was your Gleason grades and pre treatment PSA. All these "old" data are important to judge the aggressivity of your recurrence that will be highly considered in choosing a therapy. For instance, one would understand if your cancer type is ADT dependent, so that you could just continue a hormonal manipulation protocol to hold the bandit at-bay probably over 15 years. Your clinical stage would also indicate if you were diagnosed with extracapsular extensions requiring a larger field of IMRT, limiting susbtantially the possibility of rads over rads. Etc, etc.
What is your age? Are you experiencing any symptoms?

One note regarding the typical use of the PSA to define status in similar cases, I would say that the threshold PSA=2.0 + nadir indicates biochemical failure. The "Recurrence" threshold used by the many to diagnose such cases is typically the third PSA increase post biochemical failure. This is controversial for many because of the constant PSA increases seen along the months since the initial nadir (July 2013 in your case). However, one must believe and understand that those thresholds are the ones used to trigger a salvage treatment. Some doctors, in particular for Gleason 6 or 7 cases, wait till the PSA reaches as high as 10.0 ng/ml, to intervene. Some prefer earlier intervention but there is no real justification that such would guaranty better results.
The aggressivity of the cancer in that particular patient is the "rule" for fast or delayed intervention.

The treatment choice for the salvage on RT patients also differs and so would be the choice in a trigger threshold. Among the several (HIFU, Cryo, Ultrasound, Spot-rads, etc) Salvage surgery assures better outcomes if the PSA is lower than 5.0 ng/ml, but cure is only expected if cancer is contained. Spot radiation (oligometastases) is conditioned by the possibility in identifying/locating the spots. These therefore depend on the efficacy/requirements of the image study which we know that those being very diverse. Higher levels of PSA may assure better results (positive instead of false negatives).

Chemotherapy may also be a weapon if you were a Gleason 8, 9 or 10 (had pattern 5 type cells), and it could involve a series of combination with hormonal treatments. These would be palliative but proper for a longer biochemical survival.

Here is a link to a study done for salvage therapies in RT patients;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477547/ 

Best wishes in your researches. I hope you find the best.

Guys in this forum can help you to find places for image studies in the USA. You may need to travel for such an exam but it can be done in one day. You may request a family member or a friend or a neighbor to watch out your caregiver responsibilities while away.

Wishing you peace of mind.

VGama

Old Salt
Posts: 720
Joined: Aug 2014

I didn't graph this, but just by looking at the data in hespo's 7/12 post, the current (2015/16) PSA doubling time is about 7 months.

hesno
Posts: 11
Joined: Jul 2016

VGama,

Thanks for the detailed info in your last post - there is a lot there and its all important info.

As to myself, my age is 69 1/2, diagnosis in 9/2010, 6 mos lupron 01-06/2011, imrt using calypso 05-06/2011,

G7(4+3) in 4 cores - from 90-100% of core, 2 or 3 cores with G6(3+3) of around 10%

looking at imrt records, its listed as T2b N0 M0

PS - I think doubling time might be closer to what old salt put than the 14 months you mentioned, actually I think its more like 5 months but I tend to avoid plugging the numbers in very much.  You mentioned in context of doubling about the nadir in 2014 - but wouldn't my nadir be the <0.1 obtained in 2012 (ignoring the 2011 figures due to perhaps the lupron still being in my system) ?

perhaps its that difference that resulted in the view of psadt as 14 months vs the 7 months old salt mentioned ?

in any case, thanks again, I will continue reading the replies and study - already have read about ogliometatasic and term is more clear to me now.

VascodaGama's picture
VascodaGama
Posts: 2933
Joined: Nov 2010

I recalculated your PSADT this time starting with the {09/2013 - 0.2} till {05/27/2016 1.8} and the result is a doubling of 9.62 months. Old Salt may have used the data from 2015/16 which indicates PSADT=7 months. I would take this 7 months doubling as proper to judge your condition. The nadir may be the value at{09/2012 – 07/2013 - 0.1}. In any case, it seems logical to use the PSA=2.0 to declare recurrence and start a salvage therapy within six months post that thresold.

I wonder what would be your treatment choice as a salvage. The spot radiation, we discussed above, requires the identification of targets. Allowing an increase in the PSA to get a positive scan is sensitive and viable. Meanwhile you could investigate about the possibilities in having a F18 or C11 choline PET/CT exam covered or even a PET exam partly paid by you. I also think it better you discuss now with your radiologist who did the IMRT in regards to your wish of having rads over rads (oligometastatic treatment). He may have ways to get those exams included in the next RT treatment covered my your medicare.

A paliative therapy using HT or chemo can be started whenever you decide and you do not need to be so concerned with the increase of the PSA to start it. I believe that if your cancer type has responded to Lupron before, then it will respond again independently of the PSA level. What was your PSA at diagnosis before 01-2011?

Best wishes,

VG

Cheryl53
Posts: 1
Joined: Mar 2016

I am not a newcomer to this cancer club. I have been in remission and had 5 recurrences.  I am going through #5 now.  I have a similar question.  I have had 2 recent MRIs and a CT that showed metastatic disease.  Went through 10 days of radiation and my pain is still very high.  Then I did a PET and got a 'perfect' result.  I have NEVER had a perfect PET.  Especially now, with the exacerbation of pain.  Even if it's severe arthritis due to the years of cancer and treatments, according to my research, it should have picked something up.  So, I asked my nurse and she just kind of blew it off like the dr did.  Why?  This made me so mad but the city I live in does not have oncologists and I have to drive 2.5 hours to see this one.  I'm kind of stuck.    But, I need to know the truth also.  Good luck to you and all that are in the battle.  God Bless.

GeorgeG
Posts: 127
Joined: May 2017

There is a lot of good responses here and VG in particular has offered as he always does, a lot of good info, With that said, I offer the following.

The diagnosis and treatment of PC is often not an exact science with image or bloodwork verification at every step. Even the best doctors are going to have to take a best guess approach with you at some steps. My salvage treatment after RP started with zero image verification even though some of the best scans were done. That is because with the best imaging available we cannot get a 100% confirmation at a post RP PSA of less than 1.0 even though the likelyhood of failure is very high at 0.5. Even that is not 100%. The initial PSA read before any treatment has even more false negatives and positives. As has been pointed out, imaging for PC has been lacking. You build a story with the sequence of tests and images and then make an informed best guess. X percent chance of cancer given a PSA of Y. Biopsy confirms or does not all with certain levels of false negatives and positives. Then scans rule out advanced metastatic deisease ....  All of this is why the eventual decision on treatment needs your involvement. Do you want the most aggressive choices, as soon as possible, always going for maximum erradication potential regardless of the side effects. Are you the type than can live with cancer in your body and want minimum invasion and maximum confirmation. Some people go even further and want no treatment or even measurement - ever. Only you can answer those questions. Your outlook will or can be presented to you as a series of probabilities based on historic data with some spin for your particulars. The MSK charts are often used for that purpose. Of course all of this is easiest with research and the best doctors and facilities that you have access to becasue there are leading edge people doing good work. Also, there is no exactly average patient and many are at the limits of possibilities.  I know multiple people with difficult metastatic disease from different cancers (including PC) that are holding off the bandit (as VG would say) well past averages and with good quality of life. One metastatic PC patient is coming up on 20 years and going strong. Cancer is just not a black and white process, far from it. Even the relatively simple proclamation that PC is 93% cureable if gotten early is no free lunch. That's because we now know that a large percentage of those guys did not even need to go through treatment and the side effect risks because AS is getting more refined and a godd option for Gleason 6 or less with certain other traits present. Thats not comforting but its our reality. 

Building further on my case as an example. When my first 6 months of ADT ends, I have an 85% chance of being side effect free from ADT. It's not 100% but a good chance. My probability of cure after SRT is about 50%. Thas is as exactly not exact as you can get. Different doctors will present that situation with different words but none of this is 0 or 100%. Only you can know if your willing to have an X percent chance of side effects for a Y percent chance at a given outcome.

Now some people don't want any of these details. When my father got colon cancer he asked the doctor what he sould do and did exactly that. He never asked what his chances were and did not want to know. I respected that and just wished him well and gave him support.

All the best.

George

 

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