Archive - Post Operative Treatment and Treatment Upon Recurrence

Questions & Answers

POSTOPERATIVE TREATMENT FOR ADVANCED CANCER: I underwent a radical prostatectomy 5 years ago. My PSA was only 3.2. I had an aggressive Gleason grade 8 tumor, with the final pathology report showing cancer extending outside the prostate to the surgical margins. My postoperative PSA readings were 0.11 and 0.21, and I underwent postoperative radiation- hormonal therapy with Lupron injections for 1 year. Now, once again, my PSA levels are rising – 0.07, 0.16, and 0.32. I am concerned. What tests and treatments would you recommend at this point?

I would recommend that you be re-staged with a bone scan and an abdominal-pelvic CT scan. The next step would be intermittent or continuous hormonal therapy. In the future, you may need secondary hormonal therapy with abiraterone, enzalutamide, or other drugs. There is also chemotherapy if hormonal therapy stops working. Also, there is intensive research focused on treating men with advanced prostate cancer (see other QUEST articles).

METASTATIC CANCER AND PSA: My husband had a radical prostatectomy 15 years ago followed by radiation treatments. Since then, his PSA has always been 0. Recently, he was diagnosed with “metastatic bone cancer.” Could this be from his earlier prostate cancer, given his PSA remains 0?

It is very likely that it is from his prostate cancer. Some types of very aggressive prostate cancer, such as neuroendocrine cancer or very poorly differentiated cancer, do not produce much PSA. So it is possible to have metastases without an elevation of the PSA. This would be best determined by a bone biopsy. These cancers are often treated with chemotherapy rather than hormonal therapy.

METASTATIC CANCER AND PSA: My father had a radical prostatectomy for a Gleason 4 + 3 tumor that had extended outside the prostate (pathologic stage T3b). However, there was only one positive margin (at the bladder neck). Seven months later, his PSA began to rise steadily from 0.04 to 0.1. Should he undergo radiation or has his cancer already metastasized?

I would recommend first “re- staging” him with a bone scan and an abdominal-pelvic CT scan. If these studies showed no metastases and the PSA continues to increase, I would recommend that he undergo salvage radiation therapy before his PSA increases too much more. There is still a good chance that salvage radiation therapy would control his tumor.

RISING PSA WITH LUPRON: I have been on continuous Lupron therapy for the past 6 years. My PSA has been undetectable until 6 months ago when it tested 0.1. My testosterone level at the time was extremely low at 20. Then a few weeks ago, my PSA increased to 0.2 and my testosterone was 28. Does this mean that my cancer is coming back? What would you recommend?

There are rare causes of false positive PSA tests, such as interfering antibodies in a patient’s blood due to an allergy to animal dander (such as from a mouse). However, a rising PSA in a patient who is receiving Lupron therapy to suppress prostate cancer usually means there are some cancer cells present that have become resistant to Lupron therapy alone. There are other drugs (such as bicalutamide, flutamide, nilutamide, ketoconazole + hydrocortisone, abiraterone, and enzalutamide) that can be added to treat these resistant cells. The question is when they should be started. The answer is probably not when the PSA is as low as 0.2, unless the rising PSA causes the patient intolerable anxiety. Some doctors recommend using these drugs intermittently, such as when the PSA reaches an arbitrary level of 4 or 10. Others recommend waiting until the patient actually begins to have symptoms from the prostate cancer before using them. I personally usually recommend it when the PSA reaches 4.

HORMONAL THERAPY AND CHEMOTHERAPY OPTIONS: I underwent a radical prostatectomy 8 years ago with a preop PSA of 38, and the cancer has come back (PSA 2.76). After three hormone shots, my PSA has dropped to 0.000. Can the cancer come back again, or if the PSA remains 0.000 for 6 months in a row am I cured?

It is unlikely that you are cured. Neither hormonal therapy nor chemotherapy is ever truly curative. However, there are now new additional drugs that can be used if the cancer becomes resistant to the hormonal shots. Here are some options:

Active Surveillance

Some experts advocate active surveillance until there is evidence of metastases or symptoms that need to be treated. In this regard, some experts question whether men with a rising PSA after radical prostatectomy or radiotherapy really need early hormonal therapy at all, and if so, debate when it should be started.

Intermittent Hormonal Therapy (IHT)

Clinical trials provide reasonable guidelines for IHT. Some physicians use a 6- to 9-month induction course of hormonal therapy until the PSA becomes undetectable, and then they check the PSA every 3 months until it reaches a certain level to resume treatment. I usually start with a 4-month course of Lupron therapy, and then restart the hormonal therapy when the PSA reaches 4. Alternatively, many wait until the PSA reaches 10. However, hormone therapy should be resumed if there is evidence that the tumor is progressing, such as the development of metastases, regardless of the PSA level. Some physicians switch to continuous therapy when the interval between cycles is shorter than 6 months, the patient develops bone metastases, or the PSA continues to rise despite the hormonal therapy. Many patients enjoy long periods off treatment. For instance, in one trial the median time off treatment after the first cycle was 20 months. Intervals shorten with later cycles. Approximately two-thirds of patients switch to continuous therapy by the third cycle. In contrast, for patients with metastatic disease, it has been shown that overall survival is slightly better with continuous therapy. Therefore, I am cautious in recommending intermittent therapy to patients with metastases. Intermittent therapy provides a better quality of life, but studies show this benefit diminishes over time. This suggests that hormonal therapy impacts the quality of life, even when it is given intermittently early in treatment.

Available Medications

Androgen-axis inhibitors: two new androgen-axis inhibitors, abiraterone and enzalutamide, are for use in patients who no longer respond to primary hormonal therapy.

Abiraterone blocks production of male hormones produced by tissues other than the testicles, including selfstimulating hormones produced by tumor cells. Patients need to be monitored closely because Abiraterone can produce high blood pressure, low potassium and fluid retention, which can be prevented with oral prednisone 5 mg by mouth twice a day. Abiraterone has been tested both before and after chemotherapy with taxotere, and has been shown to prolong survival by approximately 1 year.

Enzalutamide has also been shown to reduce PSA in more than half of patients who no longer respond to standard hormonal therapy and prolong overall survival by a median of 4 months. Enzalutamide does not require prednisone, but it can produce fatigue, diarrhea, hot flashes and rarely, seizures.

Cipuleucel T Immunotherapy (Provenge) is a vaccine therapy that has been shown to prolong overall survival by 4 months in men with minimal or asymptomatic metastatic hormoneresistant prostate cancer. However, in one trial, patients with a baseline PSA below 22 had an estimated improvement in survival of 13 months compared to 2.9 months in those with the highest PSA levels. With Provenge, there are no markers or predictors of response, such as a decline in PSA or improvement of bone scan.

Radium-223 is a radioactivityemitting drug that is given intravenously. It has shown a significant improvement in overall median survival from 11 to 14 months. Because it works by a non-hormonal mechanism, in the future it might be shown to increase the responses with developed drugs that work through blocking hormone actions.

Cabozantinib is a new enzyme (tyrosine kinase) inhibitor that blocks abnormal genetic mechanisms responsible for the resistance of tumor cells to hormonal therapy. In preliminary studies, up to three-fourths of men respond with improvement in bone scans (responses are stunning at 12%), reduced cancer-induced pain and improved cancer progression-free survival, and its side effects are relatively modest. Soon, cabozantinib also may become a significant addition to the treatment options for men with hormone-resistant prostate cancer.

RISING PSA LEVEL AFTER RADICAL PROSTATECTOMY: What should I do when my PSA level begins to rise after a radical prostatectomy?

Depending upon the stage and grade of the tumor, and the preoperative PSA level, a rising PSA occurs after radical prostatectomy within 7 years in about 20% of patients who were thought to have cancer that was contained within the prostate before surgery.

In about 70% of these patients in this 20% category, the PSA level will return to the undetectable range following radiation treatment to the bed of the prostate. Based on our data, the PSA has remained in the undetectable range in about 70% of those patients for as long as we have followed them (70% of 70% equals about 50% overall long-term favorable response.

These findings suggest that the cause of the rising PSA is tumor cells remaining in the bed of the prostate in about 70% of those patients. About half of all patients with a rising PSA level either have the tumor cells that are outside the pelvis or have tumor cells in the pelvis that are resistant to the doses of radiotherapy that can be safely given.

With postoperative radiotherapy, there is concern that the bladder and rectum may have some permanent damage, and this damage does occur to a chronic bothersome degree in about 3% to 4% of patients who receive the prescribed dose of 6400 cGy at 180 cGy per day.

Radiotherapy also significantly reduces erections in about half of patients and may decrease urinary continence in a small percentage as well. However, current evidence suggests that a lesser dose that would completely avoid bladder and rectal complications would be less effective in eliminating all of the cancer cells.

In the “worst case scenario,” a patient could have chronic inflammation of the bladder and rectum with or without bleeding and still have the PSA rise and have to be treated with hormonal therapy as well.

For this reason, some patients who have a very slowly rising PSA after a long interval following surgery correctly assume that their tumor is not highly aggressive and elect not to receive radiation therapy, but rather opt for hormonal therapy either immediately or in the distant future, if necessary.

However, patients with slowly rising PSA long after surgery are the very patients who respond best to radiation therapy. So, it is a difficult decision to make. The patient must balance the potential benefits of the radiation therapy completely eliminating the cancer against the risks of long-term side effects.

Erections can be restored in nearly all patients, accomplished with oral Viagra, intra urethral MUSE suppositories, injections of prostaglandin into the side of the penis, a vacuum erection device, or a penile prosthesis (surgery required). Although each of these options has its drawbacks, the ability to have sexual relations may outweigh the drawbacks for many patients and their partners.

POST SURGERY OPTIONS AFTER RISING PSA: My husband has been advised to receive treatment for a rising PSA after a RRP 11 months ago. He has received conflicting advice as to whether he should pursue radiation alone or have hormone treatments prior to radiation.

There is little disadvantage for taking hormonal therapy for one month before, during and for a month or two after radiotherapy. It is helpful in high Gleason grade tumors treated primarily with radiotherapy. If the Gleason grade is less than 7, it is probably unnecessary.

POST SURGERY OPTIONS AFTER RISING PSA: My husband has been advised to receive treatment for a rising PSA after a RRP 11 months ago. He has received conflicting advice as to whether he should pursue radiation alone or have hormone treatments prior to radiation.

There is little disadvantage for taking hormonal therapy for one month before, during and for a month or two after radiotherapy. It is helpful in high Gleason grade tumors treated primarily with radiotherapy. If the Gleason grade is less than 7, it is probably unnecessary.

RISING PSA AFTER HORMONAL THERAPY: My grandfather was diagnosed with cancer about 1 year ago. His local physician found a lump while doing a prostate exam. He had blood tests done and his PSA level was 65. He was diagnosed with cancer that had not spread. He decided to try injections instead of surgery. He had three injections that brought his level down to a 2.0. He went to have another blood test done recently and his PSA level has shot back up to a 30. Can you tell me what might have caused this increase after everything seemed to be going so well.

It is possible that the hormonal therapy had worn off (this should be checked). Or it is possible that his tumor has become resistant to hormonal therapy. Please see the Hormonal Therapy Explained under the Quest Article section of this website. He might need further secondary hormonal therapy or chemotherapy in the future.

My husband had a radical protatectomy and 1 month later the PSA was undetectable. Five months later the PSA is 0.1. He had the hormone shot before surgery that caused severe hot flashes, inability to sleep. What is the best treatment option for recurrence?

A PSA value of 0.1 is in the undetectable range and does not necessarily indicate a tumor recurrence. The treatment options for recurrence after radical prostatectomy are salvage radiotherapy or hormonal therapy. Please see the article on my website under Quest Articles on treatment after radical prostatectomy from the Spring 2003 issue of Quest.

Dr. Catalona: I had external beam radiation, lupron shot, and seed implants 4 years ago. PSA just moved up to 6 over last 12 months. I just had a Prostascint study (after a negative bone scan, but CT scan showed enlarged lymph nodes on one side of groin). Prostascint results showed prostate cell activity in prostate and in same area as enlarged nodes. Is this definitely a recurrence of the cancer? Should I have a biopsy of nodes, and is it feasible to remove them—could cancer be stopped at this point?

It probably is recurrent cancer. The lymph nodes should be biopsied, at least with a needle. The cancer is probably not curable by removal of the lymph nodes, but could be controlled for a period of time with hormonal therapy (and perhaps radiotherapy, as well).

My dad was diagnosed with early aggressive prostate cancer, PSA 9 with a Gleason Score of 9. He had radiotherapy and PSA went to 1.9, but it is slightly rising, it has gone up to 5.1 in 3 years. The doctor requested that he have a bone scan. My question is, shouldn’t you only have a scan if you have a high PSA? My father is 73 and is still within the PSA limit for his age.

It is unlikely that the bone scan will show metastases with a PSA of 5.2; however, some high-grade tumors do not produce much PSA and can metastasize without a high PSA level. It sounds like your father’s doctor is being appropriately cautious.

In a recent Q&A you recommended that a writer change to a 3-months PSA follow-up as a result of his PSA changing from 0 to 0.1. At 30 months post-RRP my PSA changed from 0 to <0.1 The test was in a different lab and state. Would you recommend that I also change to a 3-months schedule?

A reading of <0.1 means that it is off the scale, i.e., there is no detectable PSA by that assay. It is essentially the same as zero. So, I would not recommend changing the PSA testing interval. The factors associated with recurrence after radical prostatectomy include the Gleason grade, the preoperative PSA, the tumor volume, the status of the surgical margins, whether there is extracapsular extension of the cancer, seminal vesicle invasion, or lymph node metastases. It is multifactorial.

I am 56 years old and had laparoscopic surgery to remove my prostate about 13 weeks ago. My first PSA rating came back last week 1.9. My urologist said not to worry and get it checked in 6 weeks to make sure the lab was right. My Gleason score was 4+3 my margins were negative. Does that mean that the surgery missed some of the cancer or that the cancer cells had left the area before the operation? Do I have any hope for treatment with my PSA that high?

If the PSA is really that high after surgery, it usually does mean that there are cancer cells left behind. They can be treated with postoperative radiation therapy and/or postoperative hormonal therapy. In many cases the cancer can be controlled for a long time. There are other treatments available as well, and a lot of research is being done. So, there is hope for successful treatment.

PERSISTENTLY ELEVATED PSA AFTER SURGERY: My husband had prostate surgery and, three months later, when they took the first PSA test following surgery , his PSA was 3.3. They took another one and it was 3.1. The surgeon said he has never seen a case like this where the number was this high after surgery. Have you ever come across this? A prostascint scan showed nothing.

Yes, please review other similar Q&A. Postoperative intermittent hormonal therapy should be considered. Postoperative radiotherapy is also an option, but less likely to solve the problem when the PSA fails to become undetectable after surgery.

Can intense sexual activity raise PSA after RRP?


ADJUVANT POSTOPERATIVE RADIOTHERAPY: I had a radical prostatectomy a year and a half ago. After surgery my PSA was undetectable. (4.5 before surgery) I had a Gleason 7 with 3 three surgical margins involved with cancer. I followed that up with 8 weeks of radiation. It’s been a year since my radiation and my PSA is stillundetectable. I am now being told that I can have my PSA test every 6 months instead of every 3 months. Do you agree with this?


IS POSTOPERATIVE TREATMENT INDICATED? I had a radical prostatectomy. Age 52, Gleason 3+3, PSA 5.5 before surgery. Negative margins, Gleason 3+3, and clear lymph nodes in surgery pathology report. First PSA test post-op 7 weeks later was <0.04. Is it sufficient to only do followup PSA every 3 months as my doctor recommends, or should I ask about followup radiation, chemo or other therapy?

Based on the information you provided, there seems to be no reason for further treatment at this time. The PSA level is undetectable.

RECURRENCE AFTER RADICAL PROSTATECTOMY: “–recurrence rates as high as 40% within two years of surgery” Newsweek Magazine April 22, 2002

Considering that surgery is viewed as the “Gold Standard,” could you pleasecomment on this seemingly high percentage of recurrence?

PSA AFTER SEED IMPLANTATION: My father was treated first with external beam and then radioactive seeds. Since then his PSA levels have slowly increased from 1.7 to 2.8 to 3.4. His doctor says this is nothing to be concerned about and told him to repeat his PSA in 6 months. I would like to know what you feel about the situation.

Generally, it is not a good sign when the PSA rises after treatment. However, there is a phenomenon called “PSA bounce” in which during the first 18 months or so after radiation treatment, the PSA goes up (presumably due to radiation-induced inflammation in the prostate gland) and then later comes down. So, it is possible that the rising PSA your father is having may be due to PSA bounce. If it continues to go up, it may mean that the radiation did not cure the tumor, and then he would be well advised to consider hormonal therapy.

DOES PSA OF 0.03 INDICATE CANCER RECURRENCE: My husband had a radical prostatectomy 5 years ago. For 3 years his PSA level has come back as undetectable. For the past year his level has increased to 0.03. Does this indicate that he has cancer in another part of his body?

In my opinion, no. A PSA level of 0.03 is very low, and I would consider it to be in the “undetectable” range. I would follow PSA levels at 6 month intervals and see what happens.

ADJUVANT RADIOTHERHAPY POST-RADICAL PROSTATECTOMY: A friend of mine recently underwent radical prostatecomy and the pathology report indicated that the cancer did get out of the prostate; however, it did not go in to the lymph nodes. You told him about the radiation treatment, but is there another treatment he could do that is not so trying on him?

There are essentially three options in this setting: 1) No further treatment unless the PSA level indicates cancer recurrence or progression, 2) salvage radiotherapy that might prevent cancer recurrence or progression but has a risk for side effects (see articles elsewhere on the website about postoperative radiotherapy), and(3) adjuvant hormonal therapy that could delay significantly any cancer progression or recurrence, but it also has side effects (see Quest article on Hormonal Therapy Explained and other articles on hormonal therapy).

PERSISTENTLY ELEVATED PSA AFTER RADICAL PROSTATECTOMY: I had radical and now I am over 6 months postoperative and still have a PSA of 1.6. What now?

The persistently elevated PSA almost certainly indicates there is persistent tumor. The options would include postoperative radiotherapy, which is less successful in men whose PSA levels do not become undetectable after radical prostatectomy, hormonal therapy – either intermittent or continuous, or watchful waiting. Other options would include chemotherapy or experimental therapy. These latter two options are usually reserved for patients who have failed to respond to salvage radiotherapy or hormonal therapy. See my recent Quest article on treatment following radical prostatectomy

RISING PSA AFTER RADIOTHERAPY: My husband (65) was treated with radiation therapy for his prostate cancer. Approximately 18 months later, his PSA started to increase. He had a cat scan and it indicated something in his rib –a biopsy showed cancer. His doctors are suggesting hormone therapy and I would like to know the benefits of continual versus intermittent hormone therapy. Also, is there a specific drug that is used or are there multiple choices? What about removing the rib?

Removing the rib will not completely solve the problem because he almost certainly has other areas of tumor in his body and, therefore, needs a systemic form of treatment that would work throughout the body. Many men prefer intermittent hormonal therapy (see articles and Q&A on my website). However, intermittent hormonal therapy may be less safe in men with metastases to the bones or very aggressive tumors. If intermittent hormonal therapy is used, he should be followed very carefully with frequent PSA levels and bone scans, in my opinion.

ISOLATED PSA RECURRENCE: Does the term “isolated PSA recurrence” refer to a one-time detectable PSA reading or to PSA failure in the absence of clinical symptoms?

This term usually means that the only suggestion of persistent or residual cancer is a detectable PSA level with no abnormality that can be felt on digital rectal examination or on an imaging study.

RECURRENCE AFTER SEED IMPLANTATION: My 58 year-old friend had seed implants about three years ago. Recently his PSA results were 5.8 and his doctor is going to repeat the test one more time and then do a biopsy. If the cancer has returned, what is the next course of treatment?

He has several options ranging from no therapy, to radical prostatectomy, to cryoablation, to hormonal therapy. I believe that the best option would be intermittent hormonal therapy. Surgery is risky after radiotherapy. Further radiotherapy is usually out of the question. Freezing of the prostate has been done in such instances, but the results reported to date are inconclusive and not very promising, in my opinion.

POSTOP PSA OF 0.11: I am 48 years old and had a laparoscopic radical prostatectomy 4 months ago. Three months after surgery my PSA was 0.11. I see on your website that you feel anything under 0.3 is basically undetectable. Should I just watch the PSA every three or four months and see what happens?

In my opinion, yes. This level is very low and, if it does represent early cancer recurrence, it will eventually declare itself. The other unlikely possibility would be retained benign prostate tissue that produces a small amount of PSA.

DOES AN UNDETECTABLE PSA INDICATE A CURE: An article in the British Medical Journal (December 2000) presents empirical evidence suggesting that a nadir PSA equal to or below 0.01 ng/ml indicates cure with a 95% probability, regardless of adverse findings (high Gleason score, extracapsular extension with positive margins). Can you please comment on these findings in the light of evidence from your own experience?

A PSA level this low is a very good sign, but it does not necessarily guarantee a cure. Possibly, too few cancer cells were there to be detected or some cancer cells that aren’t producing PSA are still present. It is important for all prostate cancer patients to follow PSA levels over time.

WHEN TO HAVE POSTOPERATIVE RADIOTHERAPY I recently had a radical prostatectomy. My PSA was 4.2 and Gleason score was 4+3=7. The tumor had spread outside the capsule but was still localized. The pathology showed negative margins except in one area that was inconclusive due to being charred from the cautery knife. I entered a Phase 2 clinical trial of adjuvant taxotere. My PSA is still undectable but I do not know if I should take radiation therapy immediately or wait to see if my PSA starts to raise. One doctor has advised me to wait and see and another recommended it get as soon as possible. What would you recommend?

I usually recommend waiting 3 to 4 months after surgery and then getting it as soon as possible thereafter. However, it is best to wait until urinary continence has recovered.

PSA OF OVER 500: My 78 year old dad’s prostate cancer was detected 4 years ago with a PSA of 50. He has had no surgery – just Casodex and Zoledex every 3 months. He has stopped responding to the hormone treatments and his PSA is increasing at an alarming rate and is now over 500. He had a bone scan 5 months ago and no trace of spreading cancer was seen. He has been told he has “months” to live and there is no treatment. He has just had TURPs to make him more comfortable. The doctor is surprised he isn’t in any pain yet. Why can’t he have any treatment?

He could have more treatment. For example, he should try ketoconazole 400 mg every 8 hours with hydrocortisone 20 mg in the morning? He could also try other antiandrogens, such as flutamide and nilutamide. He could also try estrogens with appropriate precautions. Chemotherapy with docetaxel and estramustine might also be effective. If he does develop metastases to the bone, spot radiotherapy might be useful.

After having radical prostatectomy, are 3 consecutive readings of 0.1 normal?

Depending upon the assay, yes. It is very difficult to measure PSA levels accurately when they are below 0.3 ng/ml, so for practical purposes, anything less than this is “undetectable.” However, trends from zero to less than 0.1 to 0.2 usually are meaningful evidence of recurrent cancer.

My step-dad is 82 years old and he had a radical prostatectomy 14 years ago. His PSA began to rise a few years ago and he received hormone treatments for about a year, until the PSA began to rise again. He then had 2 rounds of chemo but with his advanced age, he just couldn’t handle it. Now, his PSA is over 400 and his doctor told him last September that he had about 6 months to live. Last week he began having a lot of blood in his urine. He has no pain, and we are baffled by this. How can he have advanced cancer (confirmed that it has already spread to his bones) and not be in pain?

It is possible to have very advanced prostate cancer without much pain. On the other hand, he could develop pain in the future.

My PSA level taken 3 months after laparoscopic removal of my prostrate is 1.9. If my PSA is that high again, do you feel that any therapy hormone or radiation will work for me? There were no positive margins found. My PSA before surgery was 7.4 and my cancer was in the 2B stage. My Gleason rating after surgery is now 4+3. A bone scan was done before my operation and it was negative. I am 56 years old. What are my chances of living another 5 to 10 years? What treatment would you suggest? Also do you know of any studies being made that I could volunteer for?

The PSA indicates there are still tumor cells present. Your treatment options would include postoperative radiation therapy and/or hormonal therapy. Please read the Quest articles on the website for more information. Your chances for living another 5 or 10 years are good. I would consult with your local medical center to see what other studies might be available to you.

Do you consider that PSA reading of 0.02 at 26 days post operative is a result of residual PSA still in the system or does it arise from prostate material left behind after the procedure? Pre-operative PSA was 5.2.

A PSA of 0.02 is essentially and undetectable PSA level. This is good news, especially being only 26 days after surgery. However, it is important to get follow-up testing every 6 months for 15 years.

My husband is 57 and was diagnosed with bone metastases from prostate cancer. He is getting hormonal implants every 3 months. What sort of questions should he be asking his doctor and what is the prognosis?

He should ask about the trend (the rise in his PSA level over time) in his PSA level. He should also request that his bone density be monitored. He should ask about receiving treatment for his bone density, since he has established metastases. The prognosis is uncertain in an individual patient. Some patients can remain in remission for long periods of time. (See the article, Hormonal Therapy Explained on my website: under Quest Articles.)

My husband is 47 and had a radical prostatectomy . His doctorthought eveything looked good, no lymph node or seminal vesicle involvement was found, and was also thought to be contained. His PSA at the time of surgery was 5.35. His Gleason was 7 (3+4) He had a PSA test last week that was 0.1 and his doctor had him repeat it again days later and it was a 0.12. He is suggesting to wait 6 weeks to see the PSA level and do adjuvant radiotherapy for 7 weeks. His other PSA tests over the last year have been 0.00, 0.04, 0.01. and 0.00. Is there any other reason for the jump to 0.1, and do you think we should go ahead with the radiation for safety measures?

If his PSA level is really rising, I would agree with the recommendation for postoperative radiotherapy. However, a PSA level of 0.12 is still very low, and I would not advise you to act until there is a clear trend.

What is the best post-op PSA test? Some people are reporting <.04 or >.01 but my results are <0.1 based on something called the Bayer Chemiluminescent method. Is there a more sensitive test that I should have performed?

Different manufacturers make different claims about their tests, but in reality, it is very hard to detect PSA in quantities lower than 0..1 to .3 ng/ml. So, I believe that a reading of “<0.1” is as good as zero.

Dr. Catalona peformed RP surgery on me just over 4 years ago. One of the outcomes of the surgery was a positive margin. After the initial after surgery care, my local urologist has performed DREs every six months without detecting any abnormalties and my PSA taken every six months post surgery have all been less than 0.1 which the lab calls undetectable. My local urologist suggests no radiotherapy so long as the PSA scores remain undetectable. What are the probablities of my PSA scores rising indicating that the cancer has returned, and at what PSA score level should I undergo radiotherapy?

The probabilities of the PSA eventually rising depends upon the Gleason grade, PSA, and how extensive the involvement of the margin was. I t varies considerably. You should consider postoperative radiotherapy if the PSA begins to rise and if it rises above 0.3, in my opinion. Please see Quest articles and Q&A on postoperative radiotherapy.

Hormone Therapy Before Radiation: I have a rising PSA after having a radical prostatecomy 16 months ago. I have decided to have salvage radiation. I am getting mixed opinions regarding having a short course of hormone therapy before the radiation. Do you recommend hormone + radiation therapy for a rising PSA after surgery?

Some evidence suggests that when radiation is used as the main treatment for “high risk” tumors (locally advanced or high Gleason grade), combining hormonal therapy with radiation is beneficial, although there is no proof of this benefit for salvage radiation. However, I frequently recommend it in patients with high Gleason grades (7 or higher).

RISING PSA AFTER RADICAL PROSTATECTOMY & POSTOPERATIVE RADIATION THERAPY: RRP with Gleason 4+3, pT3a, PSA 0.01 at 6 weeks, 0.019 at seven months and 0.041 at 13 months. Fully continent and nearly potent. Does this establish recurrence or more/higher PSA readings are needed before salvage RT is advisable? Can RT be more damaging when diverticulosis is present?

This question has been answered on the website. Please look through other Quest articles and Q&A. Recurrence is a distinct possibility with this pathology report. The readings are still low but are worrisome for a climbing trend. Radiation can cause more side effects in men with diverticulosis, but diverticulosis is not a contraindication to radiation therapy.

HOW MANY DECIMALS? In reading through the Q & A I note a wide variation on PSAs. While most are only carried out one decimal place (0.1 or 0.2 for instance) some are carried out as far as three decimals (.001). My question is, how low a PSA can the current technology actually measure accurately?

Virtually all commercial PSA assays are immunoassays. Using this technology, it is very difficult to accurately measure PSA levels below 0.3. Some assays report to 2, 3, or 4 decimal places. In my opinion, small differences in reported levels in this range are of questionable clinical significance.

PSA NADIR AFTER RADIOTHERAPY: Post IMRT PSA at 4 month intervals while on Casodex and Lupron has dropped from .69 to .21 and lastly .16. Is this good? When can I expect a nadir and what should I be watching for?

PSA “nadir” means the lowest PSA value reached after radiotherapy. It should go to less than 1 if the cancer has been cured. Sometimes, it bounces up because of inflammatory changes in the prostate and then returns to a low level. However, in your case, the hormonal therapy is also contributing to the low PSA level, and the true PSA reading will not become apparent until the hormonal therapy is stopped.

POSTOPERATIVE PSA LEVELS: Is the PSA reading different for a man before and after having a prostate cancer removed?

“1” is a low PSA reading for a man with a prostate, but it is a high reading for a man whose prostate has been removed. It means there are cancer cells left behind that are producing PSA.

SURVIVAL AFTER RADICAL PROSTATECTOMY: You state that 90% of patients are alive from your series of radical prostatectomy. Would not this statement – or any equivalent statement on life expectancy – be meaningful only in relation to a control group of non-treated patients?

In the most recent tabulation of my surgical series, now including nearly 5000 patients, the 10-year overall survival rate following radical prostatectomy is 94% and the 10-year prostate cancer-specific survival rate is 96%. This means that only 6% of men died of any cause within 10 years of their surgery and only 4% died of prostate cancer.

It is true that these statistics are relevant only in comparison to the results of untreated men; however, prostate cancer is seldom left completely untreated. Even in men who start out with watchful waiting, the cancer shows evidence of progression in approximately half of patients within 5 years, and these patients then seek treatment. Therefore, I do not know what the results would have been if none of these patients had been treated, but I believe that many of them would have developed metastases and more would have died from prostate cancer.

It is true that these statistics are relevant only in comparison to the results of untreated men; however, prostate cancer is seldom left completely untreated. Even in men who start out with watchful waiting, the cancer shows evidence of progression in approximately half of patients within 5 years, and these patients then seek treatment. Therefore, I do not know what the results would have been if none of these patients had been treated, but I believe that many of them would have developed metastases and more would have died from prostate cancer.

RISING PSA MANY YEARS AFTER PROSTATECTOMY: I have a rising PSA 11 years after radical removal of prostate. Does this mean cancer has returned?

Yes, it probably does. However, patients with very late rising PSA levels generally do very well with salvage radiotherapy or intermittent hormonal therapy. See Quest Articles on this topic that are posted on the website.

RISING PSA AFTER RADICAL PROSTATECTOMY: 2 years after radical prostectomy my PSA rose to .2 then leveled off for 2 years. Now it has jumped again to .3. Recent prostascint scans revealed no tissue anywhere. My urologist is suggesting radiological treatment of the bed but emphasizes “no guarantees”. Is this the best action at this time or should I wait to see if it continues to rise higher before having treatments?

In most instances, this means that there is a recurrence of the cancer that is too small to detect on the scan. In general, the lower the PSA at the time of salvage radiotherapy, the better the prospects that the salvage radiotherapy will work. You would not lose much if you delayed somewhat for further PSA measurements. You should not let the PSA rise above 1.0 before starting the radiotherapy, in my opinion.

HOW CAN PROSTATE CANCER RECUR IF IT WAS TOTALLY CONTAINED WITHIN THE PROSTATE GLAND If prostate cancer is, in fact, totally contained within the prostate at the time of a radical prostatectomy, what is the process by which there can be recurrence? Also, what is the probability that a tumor is totally contained if there are no positive lymph nodes found, no extracapsular extension, negative margins, and no metastasis identified?

It cannot recur if it is truly totally contained and the prostate gland is completely removed. However, despite the cancer appearing to be totally contained based upon the pathology report, some “rogue cancer cells” can escape. Therefore, there is always a risk for recurrence, no matter how favorable the pathology report, which is why all patients are advised to have follow-up visits. If everything looks clean on the pathology report, an approxiamately 5-30% chance of recurrence is still possible, depending upon the Gleason grade and tumor volume.

CAN SALVAGE RADIOTHERAPY CURE PROSTATE CANCER THAT HAS SPREAD BEYOND THE PROSTATE GLAND? My father has a PSA of 9. He is 57 and in generally good health otherwise. His prostate is still very smooth. Athough the pelvic scan showed nothing outside the prostate, if he has surgery and there are cells in the lymph nodes or outside of the prostate,(but not in the bones),is it terrminal? Can radiation clean up the rest outside the prostate?

If the cancer has spread outside the prostate, it is not necessarily “terminal.” I believe that salvage radiotherapy can cure some patients with limited tumor extension outside the prostate gland. Involvement of the seminal vesicles or lymph nodes makes it much less likely that cure will be achieved than if there is just microscopic spread into the tissues surrounding the prostate gland. Nevertheless, salvage radiotherapy can prevent local re-growth of the tumor in the pelvis and prevent some of the side effects associated with local recurrence of the cancer.

My husband had a prostatectomy 18 months ago. Ever since, his PSA levels, which have been checked every 6 months, have risen substantially. We now face 7 weeks radiotherapy treatment and if that is not successful, then hormone treatment, which we hope will never happen if the side-effects are as bad as described by our consultant. Please tell me what are our hopes for his long-term survival.

The side effects of hormonal treatment and radiotherapy usually are not severe. More than 90% of patients treated with radiotherapy do not have severe permanent side effects, and hormonal therapy, especially when it is administered intermittently, is also not harsh, as cancer treatments go. Some patients have prolonged remissions lasting more than a decade with hormonal therapy alone. I believe the best mindset is to “hang in there” and, hopefully, in five years, something better will be available.

PSA FOR MONITORING PROSTATE CANCER? How useful is a PSA test once a patient is diagnosed with cancer and in therapy?

PSA is an excellent marker for use during and after cancer therapy.

Some very high grade cancers do not produce much PSA and a special form of prostate cancer called a “neuroendocrine” tumor does not produce PSA. In these unusual circumstances, the PSA is not a good marker for determining the status of the disease.

But 99% of the time, PSA lets you know how the cancer is responding to the treatment.

I had radical (nerve sparing) prostatectomy 2 years ago at age 54. Pre-op, my PSA went from 0 to 8 in 1.5 years. The Gleason score was 4+3. Surgical margins were clear and no histologic evidence of exra-capsular invasion or seminal vesicle involvement. I have been monitored every 6 months post-op (now 2 years) and until this week my PSA was 0. The most recent PSA was 0.1 ng/ml. I realize that this is considered in the “undectable range, but at this point my urologist recommends repeat testing in 1 year. Is this reasonable or should I push for another PSA in 6 months?

I would advise repeating the PSA no later than 3 months. If the PSA is rising and you elect to have salvage radiotherapy, the prospects for a favorable response are better if the PSA has not risen above 1.0 ng/ml.

My husband had a radical prostatectomy 5 years ago at age 45. Gleason 8, PSA 6. No other treatment post-op. For two years, PSA stayed 0-0.1. Steady incremental increases now for 3 years with a current increase in 3 months from 2.6-3.7. Negative bone scan and negative prostacint scan. Would you advise radiotherapy with hormone treatment at this time or just radiotherapy?

I cannot advise for his individual case; however, if he chooses to have radiotherapy, I would advise that he take hormonal therapy first to lower his PSA. Radiotherapy is more successful in patients with PSA levels lower than 1 ng/ml, and hormonal therapy has also been shown to improve the results of radiotherapy in patients with high-grade tumors.

PSA WITHOUT PROSTATE GLAND: How can people develop higher PSA’s some years after they’ve had a radical prostatectomy and their prostate is gone?

With prostate cancer, as with any form of cancer, some “rogue” cells can escape from the prostate before surgery. They are so few in number that you can’t see them on any scans or detect them with blood tests. The surgeon removes the prostate and the pathologist says it looks as if all the cancer has been removed, and the PSA becomes undetectable. Still, those “rogue” cells will grow and then, later, any PSA they produce will be taken up in the bloodstream. These “rogue” cells are why it’s really important for any man who’s been treated for prostate cancer to have follow-up visits. I recommend a PSA test every six months for 15 years after the operation.

When does a patient on hormonal therapy that seems no longer to be working start looking for clinical studies at university settings?

The next step after both primary and secondary hormonal therapy have stopped working is chemotherapy with docetaxel and a glucocorticoid drug, such as dexamethasone. If this treatment no longer works, investigational clinical trials are appropriate.

My husband has been cancer free for 13 years. His recent PSA test came back 2.2 ng/mL. He had radiation immediately following his prostatectomy but no chemo or hormone treatment. Are we looking at a return of the cancer? What are his treatment options?

I think he does have a recurrence of his prostate cancer. In my opinion, he should be re-staged with a bone scan and abdominal and pelvic CT scan, and if there is no evidence of distant spread of the cancer, he should have 2 months of hormonal therapy to lower his PSA and reduce the burden of cancer cells to be treated and then have salvage postoperative radiotherapy. Please search on this website for further details related to treatment after recurrence.

I had a radical prostatectomy a year ago. Before surgery my PSA was 5 and after, it’s been in the range of 2.6 to 3.2. My urologist has not recommended further treatment and I’m concerned. Should I go to a prostate cancer center for a more comprehensive approach. And what are my treatment options?

These PSA values are too high for a successful radical prostatectomy. Depending upon the specifics of your case, I would recommend that you consider postoperative radiotherapy and/or intermittent hormonal therapy (see for articles on hormonal therapy and postoperative radiatiotherapy).

I was diagnosed with high risk prostate cancer (PSA 86, Gleason 9, stage 3) and treated with hormones + radiation. After treatment my PSA decreased to 0.1. Recently it has risen to .4. What does this mean?

It probably means there has been a recurrence of the prostate cancer and you will need further hormonal therapy in the future. There are several articles on my website explaining hormonal therapy (search for “hormonal”).

I underwent robotic prostatectomy 2½ years ago. My PSA levels remained undetectable until 1 year ago and since then have continued to rise. The VA considers my prostate cancer to be “in remission.” Should I be concerned?

The rising PSA level almost certainly indicates a recurrence of the cancer, so I would not consider your condition to be “in remission.” You should consider salvage radiotherapy.

SALVAGE RADIATION THERAPY: My husband had his prostate removed 9 months ago. His first PSA reading was 0.02, and now it is 0.04. His doctor has recommended postoperative salvage radiation therapy. Please explain.

It is difficult to accurately measure PSA when the level is less than 0.1. So, I usually consider the PSA to be in the “undetectable” range when it is below 0.1. However, an experienced doctor can reasonably judge the ultimate need for postoperative radiation therapy based on the findings on the patient’s final pathology report, such as whether the tumor had escaped the prostate, whether there was cancer at the surgical margins, seminal vesicle invasion or lymph node metastases. My practice usually is to repeat the PSA measurements at intervals of 1 to 3 months to see if there is a convincing upward trend. I usually recommend radiation as soon as the PSA reaches 0.2. An important caveat to this scenario is that some patients may have “interfering” antibodies in their blood that can produce falsely elevated PSA readings (because mouse antibodies are used in most PSA assays). They are called human anti-mouse antibodies (HAMA). There are blood tests for the presence of HAMA that should be considered for men with rising PSA levels, especially those whose final pathology report showed features that would predict a low risk of tumor recurrence. The test can be ordered through Quest Laboratories by requesting “PSA post-prostatectomy with HAMA treatment.”

POST-RADIATION PSA: Eight years after radical prostatectomy, I received radiation to the prostate bed. Now my PSA is down to 1.4. Is that good?

If all cancer has been eradicated, the PSA should be undetectable (less than 0.1). Thus, a PSA of 1.4 indicates that there is still some prostate cancer present, and you may need hormonal therapy in the future.

SLOW GROWING TUMOR AFTER SURGERY: My husband had a radical prostatectomy 19 years ago at the age of 56. His PSA was 6 with a Gleason grade of 3 + 4. He was told the margins were clean and the tumor was contained within the prostate. His PSA stayed at 0.01 for 9 years when it jumped to .11. Nine years later it was .51 and this year it has increased to 0.58. He was told he could do radiation, chemotherapy or hormonal injections, which would bring his PSA down but would not do anything to cure the cancer. He has elected to wait and watch for 1 year. What would you recommend?

This is an unusual, but not rare, occurrence. He should have a blood test for possible interfering antibodies (human anti-mouse antibodies – HAMA) that could produce a false elevation in his PSA readings. If this is not the cause, his tumor appears to be very slowly growing, so watchful waiting could be an option. However, such tumors can increase their rate of growth over time. Your husband is now approximately 75 years old. It is conceivable that postoperative radiation could cure the cancer if it is only growing in the bed of the prostate. This certainly would be one option. Hormonal therapy would delay its growth, sometimes for many years, but it would not be curative. Chemotherapy would not be recommended unless he developed metastases.

POSTOPERATIVE PSA AND PSMA PET SCAN: My father had a robotic prostatectomy with negative surgical margins. His first postoperative PSA was 0.210; 2 months later it was 0.504. What is happening? Is the rise of PSA correlated with a cancer recurrence? The doctor recommended a PSMA Gallium PET-CT. What do you suggest?

The rising PSA indicates persistence of prostate cancer. The PSMA PET scan is a promising new test. If it showed metastases outside the pelvis, it might be a reason to treat with hormonal therapy rather than postoperative radiation; however, even in patients with distant metastases, postoperative radiation may prevent future problems with tumor recurrence in the pelvis.

HYPOFRACTIONATED RADIOTHERAPY: What is short-course radiotherapy?

With short-course radiotherapy, called hypofractionated radiotherapy, there are fewer treatment sessions with each session delivering higher doses of radiation. It has the potential to be more convenient but there are questions about its effectiveness and side effects. Three recent trials compared three different short courses (hypofractionated) of radiotherapy with three different long courses (conventional) of radiotherapy. The CHHiP trial reported that 20 days of (60Gy) is not less effective than 37 days (74Gy) for both disease control and side effects. The PROFIT trial testing 20 days (60 Gy) versus 39 days (78Gy) reported similar results for cancer control, although acute rectal side effects were mildly increased. The HYPRO trial comparing 19 days (64.6 Gy) versus 39 days (78 Gy) reported that the short course was not superior for cancer control, and side effects were not worse.

These trials complement other recent reports suggesting that outcomes and side effects of shorter therapy are not worse than conventional radiotherapy dose schedules. Longer-term results are needed.

EARLY SALVAGE RADIATION THERAPY: I have some questions regarding early salvage radiation therapy now that my postoperative PSA has risen to 0.18. The first is: can I begin this treatment immediately, and can I schedule it at the radiation oncology facility close to my house? How long I will be treated, and how long does each session last? Can I still work? Is sexual activity okay?

If all of the prostate cancer has been removed, the postoperative PSA should be undetectable (i.e., less than 0.1). If the PSA is higher than 0.1 and/or is convincingly rising, early salvage postoperative radiotherapy (initiated before the PSA rises much above 1.0) offers a ~75% probability that the PSA will become undetectable and remain so.

I recommend “intensity modulated radiation therapy (IMRT)” performed at a facility that has modern equipment by 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). Otherwise, continence will not continue to improve much after the radiotherapy.

If the original Gleason sum of the patient’s tumor was 8-10, I recommend adding hormonal therapy as well. Usually, I recommend a 4-month Lupron injection beginning 2 months before starting treatment and continuing for at least 1 year after completing radiotherapy. I also recommend taking a 10-day course of Casodex pills, beginning 1 day before the Lupron injection and continuing for the next 9 days. The hormonal therapy will have reversible side effects, including hot flashes, decreased interest in sexual activity, and lower energy level. Patients should cut back on carbohydrates and increase exercise to prevent loss of muscle and gain of fat while on hormonal therapy.

The radiation treatments are usually given 5 days per week for 6.5 to 7 weeks. Radiation facilities are usually very 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.

Patients usually have few 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 PSA levels should decrease over the next 6 months to 1 year, but usually decrease gradually. I recommend they be measured every 3 months after completing treatments.

CONTINUOUS HORMONAL THERAPY: I am 79 years old and my prostate cancer spread to my lymph nodes but not my bones. I have been taking Zoladex for last 18 months and my PSA is down to 0.5 from 14. Someone advised me to stop Zoladex intermittently and restart whenever PSA rises. Please kindly guide me.

Intermittent hormonal therapy would be an option for you (see previous QUEST articles by searching “intermittent hormonal therapy” at, but it is not the preferred option for men with bone metastases. In your case, it seems your tumor is aggressive, so I would recommend remaining on continuous hormonal therapy.

RISING PSA AFTER ENZALUTAMIDE: I was treated with radical prostatectomy followed by adjuvant radiation for a positive surgical margin. Then I underwent intermittent primary hormonal therapy for a rising PSA and, most recently, enzalutamide when the primary hormonal therapy no longer controlled the PSA levels. Now my PSA levels are again rising. A CT and bone scan showed no evidence of metastases. It seems to me that I am in a bit of a limbo state until metastatic disease is detected. My question is whether there is another study that I could also investigate?

You are in what I call a limbo state in prostate cancer treatment, where cancer control by hormonal therapy is waning, but the patient does not yet have measurable metastases to make him eligible for a clinical trial. Consequently, continued careful monitoring is the usual recommendation. However, please see the article on page 12 of this issue concerning treatment of men with non- metastatic prostate cancer that no longer is controlled by standard hormonal therapy. Apalutamide has been approved by the FDA, and manufacturers of enzalutamide have applied for approval in this clinical scenario. I am involved in a research project designed to develop a new immunotherapy vaccine. Part of this trial is to determine whether the vaccine can stimulate patients’ immune cells. There is no therapy part at this point in time, but hopefully there will be in the future. Patients interested in participating in the early phase of this trial provide 2 tubes of blood (10 cc) from which we harvest immune cells and try to stimulate them in the test tube and in animal models.

SALVAGE RADIATION AFTER NERVE SPARING SURGERY: Does salvage radiotherapy treat the cancerous cells possibly left on the nerves during the nerve sparing surgery?

Yes, if the cancer cells are located there. The blood supply to the nerves are adversely affected by salvage radiation therapy, but many patients continue to have erections despite this.

PSA FIFTEEN YEARS AFTER SURGERY: Fifteen years after my prostate cancer operation, my PSA has risen to 12.2. Is this figure dangerous, and what should I do?

It could be dangerous, but the prolonged time for it to become that high suggests that the recurrent cancer may be growing slowly. It is unfortunate that you let the PSA rise that high because postoperative radiation therapy given before it reached 0.3 might have been curative. Now, you should be re-staged with a bone scan and abdominal and pelvic CT scan and, depending on the results, your options would range from combined radiation and hormonal therapy, to intermittent or continuous hormonal therapy, or watchful waiting until there were metastases producing symptoms that could be treated by continuous hormonal therapy.

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