PCa progression and metastasis without detectable PSA levels?

paella
paella Member Posts: 81
in Prostate Cancer #1

 

Has anyone on this forum heard or read of prostate cancer progression after a radical prostatectomy yet without detectable PSA levels?  I’m talking about progression and metastasis with NO detectable PSA levels (<0.04 which is the current undetectable level)?  In a 2012 article in the Journal of Clinical Oncology, they report that a literature search yielded only 3 case reports going back to 1992.  I can let ya'll know why I'm asking but thought I'd see what kind of response this gets first since the detailed forum topic would be long-ish and will take me a while to compose in a cogent succinct manner.

Best - Paella

 

 

 

 

 

 

Comments

  • oldcoach
    oldcoach Member Posts: 3
    edited October 2016 #2
    pca progressionw/o psa

    i had one lymph node out of nine removed after surgery 9 months ago.  Psa still at .008.  Dr. said no further treatment at this time.  this is very confusing to me.  i would like to read that artice.  thanks  Pella

  • paella
    paella Member Posts: 81
    edited October 2016 #3
    Old Salt said:

    Curious

    Paella,

    Why are you asking; your own research shows that it's quite rare to have metastases and PSA levels less than 0.04 ng/mL. I did read once that some rare forms of prostate cancer (ductal) put out relatively little PSA.

    Why I'm asking

     

     

    I’m asking because a recent CT scan (for suspected hernia) actually showed over a dozen swollen pelvic lymph nodes.  Mac (husband) had a prostatectomy (da Vinci) in 2010 and has had undetectable PSA level (<0.04) for the six years hence.  His Urologic Oncology Surgeon said that it is unlikely to be prostate cancer.  However, the CT final report stated, “…lymphadenopathy suspicious for recurrent metastatic malignance, most likely prostate cancer”.   A week later he had a CT-guided needle biopsy of one of the lymph nodes the results of which we are anxiously awaiting.

    Paella

     

  • Old Salt
    Old Salt Member Posts: 1,505 Member
    #4
    Curious

    Paella,

    Why are you asking; your own research shows that it's quite rare to have metastases and PSA levels less than 0.04 ng/mL. I did read once that some rare forms of prostate cancer (ductal) put out relatively little PSA.

  • Old Salt
    Old Salt Member Posts: 1,505 Member
    edited October 2016 #5
    I see

    Thanks for the explanation. Please accept my support while waiting for the outcome of the lymph node biopsy.

    What was reported in 2010: Nx, N0 or N1? If Nx or N1, were any lymph nodes removed and/or analyzed during the prostatectomy?

  • paella
    paella Member Posts: 81
    #6
    Back to you

     

    Thank you for your support and interest!

     

     

     

    AJCC stage (6th edition) T3a NO MX).  Gleason was 7 (3 + 4).

     

     

     

    After his Radical Prostatectomy in 2010, the Surgical Pathology Reportindicated that the 10 studied lymph nodes were negative for carcinoma, there was no definitive lymphovascular invasion noted, nor any tumor present in seminal vesicles nor at soft tissue resection margins.  However, perineural invasion was seen and tumor was focally present in extraprostatic soft tissue. 

     

    Best - Paella

     

  • VascodaGama
    VascodaGama Member Posts: 3,701 Member
    edited October 2016 #7
    Unlocking the mystery

    Paella,

    The best way to certify doubts is to get a second opinion on CT images from another radiologist, or do another image exam this time with PSMA PET, even if the possibilities of detection are limited to cells with PSMA capability.

    In my view, the pathologist report of 2010 on the gland confirms the probability of cancer in the lymph nodes but the ones dissected by the surgeon were found "clean" by the same pathologist. However, we know that Davinci surgery limits the access to lymph nodes so that surgeons can only investigate/dissect the closer pack. Accordingly it is no surprise that some with cancer could have been left behind. After surgery the PSA becomes the only marker of treatment success and the negative results lead the doctor to question the results of CT's radiologist.
    Another fact is that there are about 24 types of prostate cancer some of them producing zero PSA. For instance, Small Cell Cancer do not produce the serum. Aggressive types of acinar adenocarcinoma become so poorly differentiated (disfigured) that cannot produce the serum. Please read this;

    http://www.cancerresearchuk.org/about-cancer/type/prostate-cancer/about/prostate-cancer-types

    http://www.wsj.com/articles/SB10001424052748703279704575334982806405218

    There is always the possibility that these thertiary type of cells were existent in the biopsy cores of 2010 but disregarded by the pathologist. They are in such fewer number that "escaped" diagnosis which chose the first numerous type (Gleason grade 3) and the second numerous risky type (Gleason grade 4). Surely, cancerous cells traped in the lymph nodes would be expected to grow for the plenty supply of blood at their "bed". Such activity would be enough for detection by a choline based contrast agent. CT limits the finding and depends much on the radiologist expertise.

    I wonder if your husband case would be of interest to the clinical trial on the 68Ga PSMA PET scan. You can discuss with his doctor about possibilities of getting involved in the trial. This is full but there are vacancies at certain clinics. The mystery can also be "unlocked" with microscopy analysis of those infested nodes:

    , “…lymphadenopathy suspicious for recurrent metastatic malignance, most likely prostate cancer”.   

    The trial;
    https://clinicaltrials.gov/ct2/show/NCT02488070

    Best wishes,

    VGama

  • paella
    paella Member Posts: 81
    edited October 2016 #8
    VascodaGama said:

    Unlocking the mystery

    Paella,

    The best way to certify doubts is to get a second opinion on CT images from another radiologist, or do another image exam this time with PSMA PET, even if the possibilities of detection are limited to cells with PSMA capability.

    In my view, the pathologist report of 2010 on the gland confirms the probability of cancer in the lymph nodes but the ones dissected by the surgeon were found "clean" by the same pathologist. However, we know that Davinci surgery limits the access to lymph nodes so that surgeons can only investigate/dissect the closer pack. Accordingly it is no surprise that some with cancer could have been left behind. After surgery the PSA becomes the only marker of treatment success and the negative results lead the doctor to question the results of CT's radiologist.
    Another fact is that there are about 24 types of prostate cancer some of them producing zero PSA. For instance, Small Cell Cancer do not produce the serum. Aggressive types of acinar adenocarcinoma become so poorly differentiated (disfigured) that cannot produce the serum. Please read this;

    http://www.cancerresearchuk.org/about-cancer/type/prostate-cancer/about/prostate-cancer-types

    http://www.wsj.com/articles/SB10001424052748703279704575334982806405218

    There is always the possibility that these thertiary type of cells were existent in the biopsy cores of 2010 but disregarded by the pathologist. They are in such fewer number that "escaped" diagnosis which chose the first numerous type (Gleason grade 3) and the second numerous risky type (Gleason grade 4). Surely, cancerous cells traped in the lymph nodes would be expected to grow for the plenty supply of blood at their "bed". Such activity would be enough for detection by a choline based contrast agent. CT limits the finding and depends much on the radiologist expertise.

    I wonder if your husband case would be of interest to the clinical trial on the 68Ga PSMA PET scan. You can discuss with his doctor about possibilities of getting involved in the trial. This is full but there are vacancies at certain clinics. The mystery can also be "unlocked" with microscopy analysis of those infested nodes:

    , “…lymphadenopathy suspicious for recurrent metastatic malignance, most likely prostate cancer”.   

    The trial;
    https://clinicaltrials.gov/ct2/show/NCT02488070

    Best wishes,

    VGama

     

    Hello, VGama !

     

         Thanks for your input.  We are now waiting for the results from a CT-guided needle biopsy of one of the swollen lymph nodes; this took place 3 days ago, a week after the CT itself.  It takes 7 days to complete microscopy analysis, get markers, do staging, etc., so we’re talking about the 25th or 26th of October before we know anything microscopy-wise (next week). 

     

         Here’s one of my questions to you:  In Mac’s case was it the perineural invasion and/or the extraprostatic extension in the soft tissue that alerted you to confirm the probability of his having had cancer in the lymph nodes back in 2010?  You indicate that a daVinci surgeon, being limited to lymph node access, would only dissect closer nodes.  So, if those are clean (and this is determined while the surgery is still going on) does an open surgeon routinely bisect more distant nodes?     

     

         Maybe I’m placing too much faith in Mac’s pathology report from 2010, but it clearly states PROSTATIC ADENOCARCINOMA…a typical acinar adenocarcinoma; nothing rare.  And, again, no detectable PSA for 6 years.  Although, as you indicated, some aggressive types of acinar adenocarcinoma become so disfigured that they cannot produce PSA.  As Max just indicated in his message it’ll be a super-anomaly if this is recurrent metastatic PCa.  Hoping for the best.

     

         Thanks for the articles you suggested…also the clinical trial.  Here’s a version of that Wall Street Journal article doesn’t require a subscription.   http://www.wsj.com/articles/SB10001424052748703279704575334982806405218

     

         Again, thanks - Paella

     

  • paella
    paella Member Posts: 81
    edited October 2016 #9
    I believe you are absolutely right

    and I will be happy to share the biopsy results here!   Thank you so much, as always! - Paella

  • Max Former Hodgkins Stage 3
    Max Former Hodgkins Stage 3 Member Posts: 3,817 Member
    edited October 2016 #10

    Paella,

    Your first post quotes from the Journal of Clinical Oncology, 2012.  A study gleaned the results of 21 years of statistical data regarding prostate cancer cases and PSA readings. Your post does not say if this data came just from the US, or was multinational.  But let's do some math.

    IF it was JUST from the US, we know that their are about 180,000 new cases of PCa in the US annually (actually more according to the American Cancer Society, but I have rounded downward).     180,000 x 21 years = 3,780,000 total cases, but of course, MOST of these will NOT ever become metastatic. 

    If we assume metastasis for only 10%, we still have 378,000 men (the actual percentage of all PCa cases that are discovered at Stage 4 or that at some point become Stage 4 is way over 10%, but I am being conservative here). 

    The study is also apparantly limited to men who had radical prostectomy -- surgical removal of the prostate.  Since in the US roughly half of all first-line treatments of new PCa are RP, this would cut the number in half again, but let us be more conservative still, and estimate that only 40% received RP.

    378,000 x .4 = 151,000.  These 151,000 divided by the three (3) with no detectable PSA = 1 patient in  50,333.  As I noted, my percentages are highly conservative, and the real occurence of such cases is probably much lower.

    IF the study did use European or other nationals also, then the percentage of men with metastatic and no PSA is even smaller still.

    I don't know, but probably about the same liklihood as being hit by lightning and a bus at the same time in Dodge City Kansas.  In other words, a turly microscopic liklihood.

    I found Vasco's insights and analysis to be brilliant and as usual, well-informed.  But is seems the liklihood of stage 4 PCa with no PSA detection at all is profoundly small. I hope you share his biopsy results here when they come back, since this is an extremely odd case,

    max

  • Max Former Hodgkins Stage 3
    Max Former Hodgkins Stage 3 Member Posts: 3,817 Member
    #11
    paella said:

    I believe you are absolutely right

    and I will be happy to share the biopsy results here!   Thank you so much, as always! - Paella

    My friend

    I should perhaps mention that Paella is my dear friend from the Lymphoma Board, where she has been batteling advanced disease herself, with severely harsh treatments, but she is recovering well, and her prognosis now is excellent.

    Between her own sickness and her husband's bizarre case, they have truly been dragging a dog sled through hell !

    Bless you P, and I pray for good news,

    max

  • VascodaGama
    VascodaGama Member Posts: 3,701 Member
    edited October 2016 #12
    My lay opinion

    Paella,

    Yes. The info you share from the pathologist report is evident for extraprostatic extensions. Apart from that, there is no information in regards to any hypogonadism status or hormonal manipulation that could mask the PSA. The classification of pT3a pN0 was judged correct at the time because the set of lymph nodes investigated were negative. The present category would be N1 if PCa is confirmed this time. Physicians did the right job based on available information. The only suspicious element that could have ringing the alarm was the comment:

    "......perineural invasion was seen and tumor was focally present in extraprostatic soft tissue."

    Mac's doctor after surgery weigh his decision more on the comment on the lymph nodes  "....10 studied lymph nodes were negative" and such preferences were verified by the continuous low levels of PSA. I believe that he would have suggested adjuvant RT if the PSA had shown variations.
    Some doctors would take the Gleason rate of 4 as cautious (Gs7=intermediate risk for metastases verified by the pathologist) and would suggest a salvage therapy to assure the RP outcome.

    In any case nothing yet is conclusive of recurrence. The biopsy will provide the answer and I would suggest you to have a PSA done at a different laboratory.

    I cross my fingers for a negative finding. It would mean remission forever.

    Best wishes for both of you.

    VGama

  • xNTP
    xNTP Member Posts: 38 Member
    edited October 2016 #13
    Old Salt said:

    Curious

    Paella,

    Why are you asking; your own research shows that it's quite rare to have metastases and PSA levels less than 0.04 ng/mL. I did read once that some rare forms of prostate cancer (ductal) put out relatively little PSA.

    WBC, NLR, PLR

    Paella, do you see a shift up in WBC or in neutrophil to lymphocyte ratios (2:1, then 3:1, 4:1...) or platelets and platelet-lymphocyte ratio?  This happens nonspecifically with a lot of advanced cancers, as well as other causes. 

    Guys, this is also part  of why I ask about baseline biomarkers. 

  • paella
    paella Member Posts: 81
    edited October 2016 #14
    Update from Paella

     

    Thanks again, Max (et al), for writing.  Turns out that there is no prostate cancer progression.   Actually worse news, as if we needed it.  We had a call on Saturday (1 week ago today; 10/22) from Mac’s Urological Surgeon with a report on the CT-guided needle biopsy of about a dozen swollen lymph nodes.  Hearing from a doctor on Saturday while she’s waiting for a plane is simply terrifying.  Particularly terrifying is what she had to say.  Briefly, the lymph node biopsied was found to be metastasized cancer most probably from an Upper GI organ or from the Pancreatobilliary tract, although she verbally used the term “cancer of unknown primary”…apparently not a good thing at all.  “Poorly differentiated” is also not a good thing.  The good news is that we are very quickly (on 11/1) getting into see a City of Hope oncologist who specializes in Upper GI & Pancreas.   We are both super-stressed and worried.  More tests are certain to be coming up but we may learn at least a bit more in 3 days.

     

    Since I told you I’d include it, here is the written part of the CT-guided lymph node biopsy report (which I didn’t receive until Wednesday 10/26):

     

    Diagnosis:    L Retroperitoneal

     

    • Poorly differentiated carcinoma involving fibrous connective tissue

    • Microscope description (results – paraffin immunohistochemistry):

      CK7                                 Focally positive in tumor cells      (upper GI)

      CK20                              Negative in Tumor Cells                 (lower GI)

      CDX-2                            Focally positive in tumor cells      (pancreatobilliary tract)

      GATA-3                         Negative in Tumor Cells                

      TTF-1                             Negative in Tumor Cells                               

      SYNAPTOPHYSIN         Negative in Tumor Cells                

      CHROMOGRANIN       Negative in Tumor Cells                

      S100                               Negative in Tumor Cells                

      Pax-8                            Negative in Tumor Cells

      NKX3.1                         Negative in Tumor Cells

      PSA                                Negative in Tumor Cells

      CK5/6                            Negative in Tumor Cells

      P63                                Negative in Tumor Cells (Weak Cytoplasmic Stain)

     

    INTERPRETATION:  The immunohistochemical staining features are suggestive of tumor from upper gastrointestinal or pancreatobilliary tract.  Negative staining results argue against tumor from lower GI, urothelial, renal, prostatic, neural or melanocytic origin.  No neuroendocrine differentiation is seen based on negative staining.

     

    Trying to stay positive - Paella

     

     

     

  • Old Salt
    Old Salt Member Posts: 1,505 Member
    edited October 2016 #15
    Very sorry to read that

    I am sure that all of us wish you and your husband strength with this unexpected and negative development.

    We hope that the City of Hope specialist(s) will be able to develop a protocol for a positive outcome.

    I will certainly be thinking about you and your husband!

  • Max Former Hodgkins Stage 3
    Max Former Hodgkins Stage 3 Member Posts: 3,817 Member
    #16
    paella said:

    Update from Paella

     

    Thanks again, Max (et al), for writing.  Turns out that there is no prostate cancer progression.   Actually worse news, as if we needed it.  We had a call on Saturday (1 week ago today; 10/22) from Mac’s Urological Surgeon with a report on the CT-guided needle biopsy of about a dozen swollen lymph nodes.  Hearing from a doctor on Saturday while she’s waiting for a plane is simply terrifying.  Particularly terrifying is what she had to say.  Briefly, the lymph node biopsied was found to be metastasized cancer most probably from an Upper GI organ or from the Pancreatobilliary tract, although she verbally used the term “cancer of unknown primary”…apparently not a good thing at all.  “Poorly differentiated” is also not a good thing.  The good news is that we are very quickly (on 11/1) getting into see a City of Hope oncologist who specializes in Upper GI & Pancreas.   We are both super-stressed and worried.  More tests are certain to be coming up but we may learn at least a bit more in 3 days.

     

    Since I told you I’d include it, here is the written part of the CT-guided lymph node biopsy report (which I didn’t receive until Wednesday 10/26):

     

    Diagnosis:    L Retroperitoneal

     

    • Poorly differentiated carcinoma involving fibrous connective tissue

    • Microscope description (results – paraffin immunohistochemistry):

      CK7                                 Focally positive in tumor cells      (upper GI)

      CK20                              Negative in Tumor Cells                 (lower GI)

      CDX-2                            Focally positive in tumor cells      (pancreatobilliary tract)

      GATA-3                         Negative in Tumor Cells                

      TTF-1                             Negative in Tumor Cells                               

      SYNAPTOPHYSIN         Negative in Tumor Cells                

      CHROMOGRANIN       Negative in Tumor Cells                

      S100                               Negative in Tumor Cells                

      Pax-8                            Negative in Tumor Cells

      NKX3.1                         Negative in Tumor Cells

      PSA                                Negative in Tumor Cells

      CK5/6                            Negative in Tumor Cells

      P63                                Negative in Tumor Cells (Weak Cytoplasmic Stain)

     

    INTERPRETATION:  The immunohistochemical staining features are suggestive of tumor from upper gastrointestinal or pancreatobilliary tract.  Negative staining results argue against tumor from lower GI, urothelial, renal, prostatic, neural or melanocytic origin.  No neuroendocrine differentiation is seen based on negative staining.

     

    Trying to stay positive - Paella

     

     

     

    Wrenching

    Paella,

    This is wrenching, very bad news.

    Curability of metastatic organ cancers vary by where they began, so determing that might be the focal point at this moment. I'm glad you are going to one of the best tretment centers. 

    Praying for you two...this is such a "piling on," with the medical ordeal you have been through lately.

    max

  • VascodaGama
    VascodaGama Member Posts: 3,701 Member
    #17
    Let's find newer weapons and trash the bandit

    I am very sorry for the findings. I hope the consultation with the specialist brings you peace of mind. I believe your experience against cancer will give you the strengths needed in this new battle. It is the beginning, loads of stress and much to learn but Mac will win again.

    Best wishes and luck.

    Sincerely,
    VGama

     

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