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What Causes Hematuria Post Radiation Therapy?
Question: I have a question about my Mom's health condition.
She is a 77 year old woman.
She had an uterine cancer 22 years back.
It was treated with partial hysterectomy and followed by radiation therapy.
Recently she has been having occasional symptoms of gross hematuria for past 3 months.
Below is the list of gross hematuria episodes and diagnostic tests done to find the cause of the bleeding.
***Gross Hematuria History***
-----------------------------
July 1st week - Noticed blood in the urine 2-3 times.
8/24/16 to 8/27/2016 - Noticed blood in the urine 3 times
***9/15/2016 - Profuse bleeding in night time. 10-12 bathroom visits. Most time no urine but only bleeding***
9/21-9/22 - Blood in the Urine.
***Diagnostic Test Results***
-----------------------------
1) CT Abdomen/Pelvis- IVP (Test done on 08/03/2016)
Results:
Asymmetric Irregular bladder wall thickening involving the anterior bladder wall with findings worrisome for transmural extension.
Findings suspicious for primary bladder malignancy - Transitional cell carcinoma. (TCC)
2) Cysto w/ bladder Bx and Fulguration of radiation Cystitis Test done on 08/15/2016)
Results:
Anterior bladder wall biopsy:
Mild urothelial atypia consistent with radiation cystitis.
3) ProFISH (Test done on 08/23/2016)
Dx: POSITIVE Profile With 5p15 Amplication.
The ProFISH bladder cancer FISH study detected abnormal copy numbers involving chromosomes 3, 7, 10 and/or 5p15.
A positive result requires a minimum of 5 cells which demonstrate a gain of 2 or more of chromosomes 3, 7 and 10.
Additional copies of 5p15 were observed in this sample. Additional copies of the 5p15 locus may be indicative of a more aggressive, muscle invasive carcinoma with the possible formation of a 5p isochromosome. Twenty-five cells were scored in this sample.
4) Urine Cytology (Test done on 08/23/2016)
Dx: NEGATIVE For Malignancy
Results:
Reactive urothelial cells, squamous cells, acute inflammatory cells and red blood cells.
5) Urine Cytology (Test done on 09/28/2016)
Dx:
POSITIVE for malignant cells Urothelial carcinoma, high grade
Background of benign squamous cells, acute inflammation and erythrocytes
We have following questions and concerns:
-----------------------------------------
1) She had negative biopsy result and negative first urine cyto.
But she had positive CT scan, positive FISH test and positive second urine cyto.
These results are very confusing. What should we do next to get the definitive diagnosis?
2) What are the chances she may have cancer?
3) Do radiation cystitis (RC) cause positive FISH and Urine Cytology results?
4) Is there a possibility that the bladder biopsy could have missed the cancer?
If so, what do we need to do next to confirm Dx?
5) Are there any chances that the cause of bleeding is not bladder but somewhere else?
6) What further tests you will recommend in this situation?
Thanks you very much for your help!
Appreciate your time.
She is a 77 year old woman.
She had an uterine cancer 22 years back.
It was treated with partial hysterectomy and followed by radiation therapy.
Recently she has been having occasional symptoms of gross hematuria for past 3 months.
Below is the list of gross hematuria episodes and diagnostic tests done to find the cause of the bleeding.
***Gross Hematuria History***
-----------------------------
July 1st week - Noticed blood in the urine 2-3 times.
8/24/16 to 8/27/2016 - Noticed blood in the urine 3 times
***9/15/2016 - Profuse bleeding in night time. 10-12 bathroom visits. Most time no urine but only bleeding***
9/21-9/22 - Blood in the Urine.
***Diagnostic Test Results***
-----------------------------
1) CT Abdomen/Pelvis- IVP (Test done on 08/03/2016)
Results:
Asymmetric Irregular bladder wall thickening involving the anterior bladder wall with findings worrisome for transmural extension.
Findings suspicious for primary bladder malignancy - Transitional cell carcinoma. (TCC)
2) Cysto w/ bladder Bx and Fulguration of radiation Cystitis Test done on 08/15/2016)
Results:
Anterior bladder wall biopsy:
Mild urothelial atypia consistent with radiation cystitis.
3) ProFISH (Test done on 08/23/2016)
Dx: POSITIVE Profile With 5p15 Amplication.
The ProFISH bladder cancer FISH study detected abnormal copy numbers involving chromosomes 3, 7, 10 and/or 5p15.
A positive result requires a minimum of 5 cells which demonstrate a gain of 2 or more of chromosomes 3, 7 and 10.
Additional copies of 5p15 were observed in this sample. Additional copies of the 5p15 locus may be indicative of a more aggressive, muscle invasive carcinoma with the possible formation of a 5p isochromosome. Twenty-five cells were scored in this sample.
4) Urine Cytology (Test done on 08/23/2016)
Dx: NEGATIVE For Malignancy
Results:
Reactive urothelial cells, squamous cells, acute inflammatory cells and red blood cells.
5) Urine Cytology (Test done on 09/28/2016)
Dx:
POSITIVE for malignant cells Urothelial carcinoma, high grade
Background of benign squamous cells, acute inflammation and erythrocytes
We have following questions and concerns:
-----------------------------------------
1) She had negative biopsy result and negative first urine cyto.
But she had positive CT scan, positive FISH test and positive second urine cyto.
These results are very confusing. What should we do next to get the definitive diagnosis?
2) What are the chances she may have cancer?
3) Do radiation cystitis (RC) cause positive FISH and Urine Cytology results?
4) Is there a possibility that the bladder biopsy could have missed the cancer?
If so, what do we need to do next to confirm Dx?
5) Are there any chances that the cause of bleeding is not bladder but somewhere else?
6) What further tests you will recommend in this situation?
Thanks you very much for your help!
Appreciate your time.
Brief Answer:
Most likely Radiation Cystitis only
Detailed Answer:
Hi,
In the context of your mother having received radiation for her uterine cancer, it is almost inevitable that the bladder has also received some dose of radiation. Quite often, this radiation cystitis presents as recurrent episodes of haematuria, and it looks like that's what your mother has gone through.
This post-radiation sequelae can result in mild thickness of bladder wall, and this can be interpreted on The CT Scan as suspicious for bladder cancer. Same goes for the cytology. Radiation can alter normal bladder cells and therefore an expert cytologist should ideally view the slides bearing this in mind
The single best test for bladder malignancy is still a conventional biopsy. If fulguration of bleeding was done at cystoscopy, and yet if the urologist could not detect a growth in bladder, it is unlikely that there is a significant growth, though it will always be very difficult to aver with complete confidence that such a growth does not exist.
I am afraid FISH is not my specialty, and I will be unable to opine regarding the findings of FISH.
The next you could do is to get an oncologist's opinion. Newer tests such as NMP 22 do exist but keep in mind that there could be significant lack of sensitivity and specificity because of prior radiation.
If fulguration has stopped the bleeding, then the bladder or urethra should probably be the only cause of blood in urine.
Plenty of fluids should help. Ask your doctor regarding use of drugs like Pentosan Polysulfate which have a record of taking care of conditions like radiation cystitis.
I hope your mother is not on blood thinners like ecospirin or clopidogrel. Use of such drugs may have to be modified.
Glad to have been of help.
Best wishes.
Most likely Radiation Cystitis only
Detailed Answer:
Hi,
In the context of your mother having received radiation for her uterine cancer, it is almost inevitable that the bladder has also received some dose of radiation. Quite often, this radiation cystitis presents as recurrent episodes of haematuria, and it looks like that's what your mother has gone through.
This post-radiation sequelae can result in mild thickness of bladder wall, and this can be interpreted on The CT Scan as suspicious for bladder cancer. Same goes for the cytology. Radiation can alter normal bladder cells and therefore an expert cytologist should ideally view the slides bearing this in mind
The single best test for bladder malignancy is still a conventional biopsy. If fulguration of bleeding was done at cystoscopy, and yet if the urologist could not detect a growth in bladder, it is unlikely that there is a significant growth, though it will always be very difficult to aver with complete confidence that such a growth does not exist.
I am afraid FISH is not my specialty, and I will be unable to opine regarding the findings of FISH.
The next you could do is to get an oncologist's opinion. Newer tests such as NMP 22 do exist but keep in mind that there could be significant lack of sensitivity and specificity because of prior radiation.
If fulguration has stopped the bleeding, then the bladder or urethra should probably be the only cause of blood in urine.
Plenty of fluids should help. Ask your doctor regarding use of drugs like Pentosan Polysulfate which have a record of taking care of conditions like radiation cystitis.
I hope your mother is not on blood thinners like ecospirin or clopidogrel. Use of such drugs may have to be modified.
Glad to have been of help.
Best wishes.
Above answer was peer-reviewed by :
Dr. Nagamani Ng
Hello Dr. Sasanka -
Thank you very much for your response and the expert advice.
Based on your response, I have following follow-up questions:
1) My mother had uterine cancer 22 years back. And had radiation therapy.
She never had hematuria in the past. She first time noticed blood in the urine 3 months back.
Is it possible to have radiation cystitis after 22 years and episodes of hematuria?
2) Are there chances that urologist may have missed the tumor during cystoscopy?
3) Is blue-light cystoscopy more accurate compared to white-light cystoscopy?
4) She had profuse bleeding in night time few weeks back. 10-12 bathroom visits. Most time no urine but only bleeding (9/15/2016). Is it consistent with RC or something else?
5) If bladder is not cause of bleeding, what organs are the possible cause and what tests needed to rule out the possibility?
Thanks again for your time and expert advice!
Best Regards
Thank you very much for your response and the expert advice.
Based on your response, I have following follow-up questions:
1) My mother had uterine cancer 22 years back. And had radiation therapy.
She never had hematuria in the past. She first time noticed blood in the urine 3 months back.
Is it possible to have radiation cystitis after 22 years and episodes of hematuria?
2) Are there chances that urologist may have missed the tumor during cystoscopy?
3) Is blue-light cystoscopy more accurate compared to white-light cystoscopy?
4) She had profuse bleeding in night time few weeks back. 10-12 bathroom visits. Most time no urine but only bleeding (9/15/2016). Is it consistent with RC or something else?
5) If bladder is not cause of bleeding, what organs are the possible cause and what tests needed to rule out the possibility?
Thanks again for your time and expert advice!
Best Regards
Brief Answer:
Possible to miss small tumours
Detailed Answer:
Hi again.
It is quite possible to develop radiation cystitis even 20 years after treatment for cervical cancer or uterine cancer. We see it reasonably frequently.
It's possible for a small tumour to have been missed by even an expert Urologist. Blue Light Laser helps reduce chances of missing such tumours and can be recommended for your mother.
The fact that your mother had profuse haematuria is quite consistent with radiation cystitis.
A test which can be done for further evaluation is MRI scan, especially if bleeding recurs.
Hope your mother does well.
Regards.
Sasanka.
Possible to miss small tumours
Detailed Answer:
Hi again.
It is quite possible to develop radiation cystitis even 20 years after treatment for cervical cancer or uterine cancer. We see it reasonably frequently.
It's possible for a small tumour to have been missed by even an expert Urologist. Blue Light Laser helps reduce chances of missing such tumours and can be recommended for your mother.
The fact that your mother had profuse haematuria is quite consistent with radiation cystitis.
A test which can be done for further evaluation is MRI scan, especially if bleeding recurs.
Hope your mother does well.
Regards.
Sasanka.
Note: Consult a Urologist online for consultation about prostate and bladder problems, sexual dysfunction, kidney stones, prostate enlargement, urinary incontinence, impotence and erectile dysfunction - Click here.
Above answer was peer-reviewed by :
Dr. Yogesh D
Answered by
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