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My postoperative PSA readings that were in the undetectable range now are rising to 0.06. What does this mean?
The PSA value of 0.06 ng/mL is actually in the “undetectable” range. It is very difficult to measure PSA accurately when it is present in concentrations less than 0.1 ng/mL. However, if the PSA does creep up, it is usually due to a recurrence of prostate cancer, which should be treated with salvage radiation therapy. Alternatively, it could be a false-positive result.
HAMA PSA test: Some patients develop antibodies in their blood as an allergic response to an antigen in the environment, such as animal dander (HAMA stands for human anti-mouse antibodies), or as an “auto-immune response" to a tissue antigen in their own body, such as Crohn’s disease, lupus, or rheumatoid arthritis. These antibodies can interfere with the antibodies used in the PSA tests and produce false-positive results.
There is a special PSA blood test, also available at Quest laboratories (no relationship with our QUEST newsletter) called, “post-prostatectomy PSA with HAMA treatment" that measures the PSA, removes the interfering HAMA antibodies, and then re-measures the PSA again. I recommend that you get this test.
There are several management options that you may wish to consider:
Watchful waiting: If HAMA antibodies are not the cause of your rising PSA, your tumor appears to be very slow-growing, so watchful waiting could be an option. However, such tumors can increase their rate of growth over time.
Hormonal therapy would delay its growth, sometimes for many years, but would not be curative.
Chemotherapy would not be recommended unless you developed metastases that were not responsive to hormonal therapy.
Salvage radiation therapy:
If your PSA increases to higher than 0.1 and/or is convincingly rising, and HAMA antibodies are not the cause, I usually recommend early salvage postoperative radiotherapy (initiated before the PSA rises much above 1.0), which offers 75%-85% probability that the PSA will become undetectable and remain so in patients with low-grade, late-recurring tumors but 50% to 65% in patients with high-grade tumors. This certainly would be a good option.
I usually recommend “intensity modulated radiation therapy (IMRT)" performed at a facility that has modern equipment and a radiation oncologist who is experienced in treating prostate cancer patients. Before starting the radiotherapy, the patient should have achieved complete urinary continence (i.e., no pads).
Concomitant hormonal therapy along with radiation treatments is known to enhance the effectiveness of radiotherapy, especially for high-grade cancers. Therefore, if the original Gleason sum of the tumor was 8-10, I recommend adding hormonal therapy as well. The hormonal therapy has reversible side effects, including hot flashes, decreased interest in sexual activity, and lower energy levels. Patients should cut back on carbohydrates and increase exercise to prevent loss of muscle and gain of fat while they are on hormonal therapy. Some radiation oncologists use hormonal therapy in all patients, but I do not believe the benefits outweigh the risks and side effects in patients with your tumor features.
Traditionally, radiation treatments have been given 5 days per week for 6.5 to 7 weeks. Radiation facilities are usually accommodating about scheduling treatments early in the morning or in the evening for patient convenience. Each session lasts only a few minutes. There is no reason not to engage in sexual activity during radiation treatments.
Patients usually have few permanent side effects. Some may have some rectal burning toward the end of treatment, and some complain of fatigue. Approximately 90-95% have no permanent side effects, but 5-10% may have some permanent damage to the bladder and/or rectum that is manifested by urinary frequency, diarrhea, or blood in the urine or stool from time to time. The blood supply to the nerves is adversely affected by salvage radiation therapy, but many patients continue to have erections despite this. The PSA levels should decrease over the next 6 months to 1 year but usually decrease gradually.
The downsides of the standard treatment regimens are the time commitment, as well as the prolonged length of time that men have to deal with side effects. Recently – especially in the COVID crisis – many radiation oncologists have switched to more convenient shorter-course radiotherapy, called hypofractionated radiotherapy. There are fewer treatment sessions (5 to 20 total treatments), with each session delivering a higher dose of radiation per treatment. Hypofractionation has the potential to be more convenient. Recent clinical trials comparing different courses of hypofractionated radiotherapy for definitive treatment of prostate cancer with three different long courses (conventional) of radiotherapy reported similar results for cancer control, although acute rectal and urinary side effects were mildly increased. These trials complement other recent reports suggesting that outcomes and side effects of shorter therapy are not worse than conventional radiotherapy dose schedules, but longer-term results are needed.
You should call the department of radiation oncology at a “modern” facility near where you live or work and tell them that you need salvage radiation therapy for prostate cancer (with IMRT) and that you would like an appointment with the radiation oncologist who has the most experience in treating prostate cancer. You should address your questions about possible side effects to the radiation oncologist. They will need to perform a new abdominal-pelvic CT scan and may also want to obtain a bone scan or PET scan to determine whether cancer has spread to regions outside the pelvis.
The latest National Comprehensive Cancer Center Network (NCCN) guidelines recommend hormonal therapy before, during, and for 1 year after the course of radiotherapy. In my opinion, this is not always necessary and is something you will discuss and decide with your radiation oncologist.
Articles from my Quest newsletter provide more information on this topic: www.drcatalona.com
My testosterone level came back in the low end of the normal range. Should I begin testosterone replacement therapy?
Testosterone-replacement therapy can be given by injection, patch, gel, or underarm liquid (in increasing order of expensiveness). Patients should be monitored with at least annual and often more frequent blood counts, liver function tests, cholesterol and lipid panels, testosterone measurements, and PSA levels. Also, body weight should be monitored for fluid retention. Patients on testosterone-replacement therapy become dependent upon it because the pituitary gland is shut down by the external testosterone in the blood and thus does not normally stimulate the testicles to produce testosterone. Consequently, the testicles shrink. Another concern is the issue of tumor dormancy. Some tumors, including prostate cancers, can “wake up” after being dormant for many years. My website (www.drcatalona.com) contains an article in the Spring 2021 Quest publication on page 10 that provides more information. You should make a shared decision with your physicians on whether you would like to start testosterone replacement or not.
My PSA and Prostate Health Index levels have been trending unfavorably (rising PSA and PHI and decreasing percent free PSA). I am concerned that this may indicate the presence of prostate cancer. Please advise me on the next step in evaluation.
I recommend that you consider a prostate biopsy procedure that could be performed under
local anesthetic in the office or as an outpatient procedure in the operating room under deep
sedation. You will need to take a Fleet enema the morning of your biopsy and an antibiotic pill 2
hours before your biopsy and a second antibiotic pill at bedtime the evening of the biopsy. You
should be able to return home within an hour or two.
My prostate biopsy report indicated that there was high-grade "prostatic intraepithelial neoplasia." What does that signify?
We call this finding “PIN” for short. Another similar condition is called “atypical small acinar proliferation” that we call “ASAP” for short. They are potentially precancerous conditions that may or may not turn into cancer (25-40% do over time). Sometimes, they do not progress over decades. I recommend monitoring your PHI level every 6 months and in the future (depending on PHI results) have a prostate MRI scan and possibly a repeat biopsy.
I am having responses of insufficient duration with my intracavernosal injections. What are the options for remedy?
The first consideration is the strength of the preparation you are using and how many units you are you injecting? If more than 50 units you can order a 100 unit syringe with the same small 31 gauage 5/16 inch needle. The different strengths of the medicine we recommend most frequently are Bimix 3 or Bimix 5? The softening is due to venous leakage, but I would advise you purchase an actis venous flow controller. You can read about in the link below. http://www.phoenix5.org/sexaids/other/actis.html
The venous leak will improve as the nerves recover over time.
I have heard that there is a new “infection-free prostate biopsy procedure.” Should I have that for my upcoming scheduled biopsy?
The transperineal biopsy procedure is the latest approach that is being advocated by some urologists based on a lower risk for post-biopsy infections and a greater ability to target regions of concern in the front portion of a large prostate gland . On the other hand, it may have a higher risk for bleeding and.or urinary retention, and it usually is more uncomfortable. Therefore, many urologists perform trans-perineal biopsies in an operating room setting under deep sedation; however, some urologists perform them under local anesthesia in the clinic. In a recent meeting there were many debates between transrectal and transperineal biopsies, and there were strong advocates on both sides. There has been hope that a MRI scan of the prostate would serve as a substitute for the biopsy, but it is not an adequate substitute at this time.
I have been advised to begin hormonal therapy or ADT (androgen deprivation therapy). What are the next steps?
I usually recommend beginning with with a 10-day course of Casodex 50 mg capsules by mouth once a day. On day 2 of the capsules, you should receive a Lupron injection 22.5 mg or 30 mg in your buttock. Within a month, your blood testosterone will decreases to negligible levels and remains there for 3 to 4 months. If the treatment is to be continued beyond this time, the Lupron injection alone is sufficient on the follow-up injections without the Casodex capsules.
Three years ago, I underwent postoperative salvage radiation therapy for a recurrence of my prostate cancer. Since then, my PSA has been undetectable. Yesterday, after vigorous exercise I noticed some bright red blood in my urine? What should I do?
In patients who have undergone radiation therapy, blood in the urine is usually caused by
fragile blood vessels in the bladder that result from the previous radiation treatments (called
“radiation cystitis”. The “proper" evaluation includes a tri-phasic CT scan of the abdomen to
visualize the entire urinary tract and a look into the bladder by passing a small flexible scope
with a tiny camera on its tip up through the urethra (called “flexible cystoscopy”). It also
includes sending urine samples to rule out infection and to look for malignant cells. Usually, the
results are negative. Then, we feel reassured that radiation is the cause and do not pursue
further follow-up unless it occurs again several years later.
My DEXA bone density scan reveals moderate osteoporosis (thinning of the bones). Do I need more treatment than the recommended 1000 mg calcium, 1000 units of Vitamin D3, 30 minutes of sunshine without sunscreen daily, and weight-bearing exercise?
For patients whose DEXA scan shows a value lower than -2.5, it is recommended that they have
a bone strengthening treatment. Two of the drugs are zoledronic acid and denosumab. Both
carry some risk of jawbone problems, but this is less with denosumab than the zoledronic acid.
The zoledronic acid also carries a greater risk for kidney damage. Therefore, I recommend that
you consider having denosumab injections. The dosage of the injection is 60 mg every 6
The surgical specimen from my radical prostatectomy reported “positive surgical margins.” What should I do about that?
For patients who have any positive margins, the final hurdle is the post-operative PSA. If it is
undetectable, then they have 2 options: (1) to have post-operative radiation therapy to be
proactive (called “adjuvant” radiation therapy), and (2) not to have post-operative radiation
therapy, but to measure the PSA more frequently, i.e., every 4 months rather than every 6
months. Then, if the PSA does begin to creep up, you would get the post-operative radiation
(called “delayed salvage radiation therapy”). The current data suggests that it is okay not to
choose delayed adjuvant radiation therapy unless the pathology findings from the radical
prostatectomy are very severe.
Q1a: I noted that the MRI imaging report also indicates acute “on top of” chronic prostatitis. What treatment do you recommend to address this? Q1b: Is there anything that can be done to treat prostatitis referred to in the report? I believe this is a chronic, long-term issue as I think I recall signs of it in other test reports from the past.
A1a/b: In times past, we treated patients who had an elevated PSA with antibiotics, even though their urine was not infected. In many patients, the PSA returned to lower levels. However, the infectious disease experts have called this practice “poor antibiotic stewardship," often leading to the bowel becoming colonized with strains of bacteria that are resistant to many different antibiotics. They are correct about this. The current practice is to rely on the patient’s immune system to clear prostatitis without antibiotics. If the PSA does not return to normal, we recommend an MRI and/or biopsy as the next step. Therefore, unless the patient is symptomatic with fever and urinary tract infection, we do not treat with antibiotics. Nevertheless, once a man has prostatitis, it will likely flare up from time to time. These flare ups can be expected to be associated with fluctuations in PSA levels.
What is my prognosis when the final pathology report on my prostate gland showed the tumor was organ-confined with clear margins and no seminal vesicle involvement or lymph node metastasis? Does this guarantee that I am “cancer-free?”
With those favorable tumor features, the risk for cancer coming back is quite low but not zero. At a minimum, I recommend PSA testing every 6 months for at least 10 years and annually thereafter.
How do I interpret my latest test results? It looks as if everything is trending in the wrong direction. My PSA is over a full point higher than it was 6 months ago, and my PHI score seems to be as high as it ever was.
Your Prostate Health Index, total PSA, and percent free PSA are trending in concerning directions: The PSA is rising, the PHI is rising, and the percent free PSA that measures the extent to which your rising PSA is due to a benign condition is decreasing. On the other hand, it is reassuring that you had a negative prostate biopsy less than 6 months ago. Hence, this trend could be the result of persistent inflammation in your prostate from the biopsy procedure. Nevertheless, considering your positive family history of prostate cancer in your father and paternal grandfather, you must remain vigilant. I suggest that you repeat the PHI in 6 weeks to determine whether the unfavorable trend continues, and if so, I recommend a follow-up MRI scan of the prostate to see whether a new region of concern has appeared.
I would rate my urinary continence about 99%. I get an occasional drop but nothing significant. I've made a habit of doing 10 Kegels every morning. My question is, do I need to do these for the rest of my life or was this just for rehabilitative purposes?
I am glad to learn that your continence is now nearly complete. Most patients stop doing the Kegel exercises once it is 100%, but some continue to do them for the rest of their life. With regard to return of spontaneous erections, the injections may speed up that process. Most patients do not begin to have spontaneous erections for at least a year, but it is best not to wait a year to begin the injections. Start them right away, as this way the chances for complete return are better.
I just wanted to let you know I stopped the injections a few months ago, because I don't feel comfortable doing it (having the scar tissue from when I was doing it wrong, along with some bleeding the last few times). If there is a second best alternative you can suggest, I would like to try it or at least consider it. Perhaps, Cialis, Viagra, etc., or something else.
The pills do not materially induce erections until you are beginning to have spontaneous erections, but they marginally increase the blood flow to the genital region. So for patients who don’t want to do the injections, I recommend either the intraurethral suppositories (MUSE – they are very expensive!) or a vacuum device. You can find more information about one such device and how to use it be pasting the following link into an internet browser: https://www.youtube.com/watch?v=hqTpzgcO9nI. Your Prostate Health Index results are trending favorably: i.e., your PSA and PHI are lower but still high, and your percent free PSA is higher (which is good) but not as high as desired. These results are the similar to those 2-3 years ago, so they do not suggest the presence of a continuously growing prostate cancer. I recommend that you repeat the PHI and prostate exam in 6 months.
I am using the Bimix (papaverine 30 mg/mL and phentolamine 3 mg/mL) injection for erectile dysfunction. I put the medication in the freezer while I was waiting for the injection training session. I am keeping one vile in the fridge as I use it for the three-per-week injections. Should I worry about the quality after freezing and refrigerating?
Freezing sustains the strength of the medicine longer than simple refrigeration. With refrigeration only, the Bimix becomes weaker after three months and you may need to inject a greater volume to get the same desired effect.
Last night, there was blood in my urine. On occasion, there is also blood in my ejaculate. All of my adult life, I have gotten up about three to four times at night to urinate. Should I be doing something about this?
Blood in the urine or ejaculate is usually caused by fragile blood vessels in the bladder or prostate gland. The “proper” evaluation includes a tri-phasic CT scan of the abdomen to visualize the entire urinary tract, followed by a look into the bladder by passing a small flexible scope up through the urethra to rule out a stone or tumor somewhere in the urinary or genital tract. It also includes sending urine samples for infection and to look for malignant cells. Usually, the results are negative. Then, we feel reassured that the blood may be due to transient inflammation or infection.
I received my prescription of Bimix 30-5 (papaverine 30 mg/mL & phentolamine 5mg/mL), but I am a little confused. I received five vials and have injected myself five times, as directed. I have stored the remainder of the medications in its vial in my refrigerator. Do I need to order again or am I supposed to use the leftover medication in each vial to inject again? Could reusing the vials a second time might lead to infections?
The vials are intended for multiple uses. You can use the leftover medication, but you should ensure that you use sterile precautions (carefully wiping the vial top and injection site with alcohol) in performing the injection.
A few months ago, my PSA score went from 0.01 to 0.02 ng/mL. I waited several months to re-test due to the pandemic. The new test results are a PSA of 0.00 ng/mL. I think you would agree it can't be any better than that, right? It will be five years since my radical prostate surgery. How long until I should get re-tested?
You should be tested for 10 more years. But so far, so good!
I have a 68-year old patient with a metastatic Gleason 9 prostate cancer, diagnosed two years ago, that is progressing after hormonal therapy with abiraterone and prednisone and after chemotherapy with docetaxel (6 doses). He is in very good shape. He and his family are interested in traveling to the U.S. for a second opinion and exploring the option of new drugs in a clinical trial. May I ask you for a recommendation?
For patients who no longer respond to abiraterone/prednisone, the newer-generation apalutamide and darolutamide are frequently effective oral medications and are far better tolerated than enzalutamide. However, these drugs are prohibitively expensive unless they can be accessed in a clinical trial.
Another new approach that is being increasingly used and championed at Johns Hopkins University by Dr. Sam Denmeade is bipolar testosterone therapy that re-sensitizes castration-resistant prostate cancer to subsequent androgen deprivation therapy. An added advantage is that most patients become deconditioned (muscle loss, low energy, osteoporosis) by prolonged androgen-deprivation therapy, and the intermittent restoration of testosterone with bipolar testosterone therapy breaks that negative cycle. Your patient may be able to receive this treatment in your country at a reasonable cost. I suggest that you and he Google, “bipolar testosterone therapy prostate cancer” for further information.
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