Diagnosing a Recurrence

The PSA is the earliest sign of a problem if the cancer is returning.  The PSA typically predicts a recurrence long before the scans show a problem. It is like a barometer showing a low pressure reading in advance of a storm actually arriving.   If prostate cancer recurs, it can come back in many different locations in the body, not just in the prostate.  The most typical locations are:

1. In the prostate gland, if it was not removed.
2. In the fat and tissues that surround the prostate gland
3. In the lymph nodes in the pelvis and abdomen
4. In the bones, especially the spine, pelvic bones, and ribs.

Surgically removing the prostate gland only prevents the cancer coming back within the prostate gland itself.  It can still come back in all the other locations listed above.    No matter where the prostate cancer cells comes back in the body it will make the PSA rise.

Once we are convinced that the PSA is rising abnormally following CyberKnife, we begin the search for where the cancer is in the body.  The location of the cancer recurrence determines what treatment should be done next!!   We begin the search typically by doing CT scans and a bone scan.  If these are normal then we may consider doing another prostate biopsy.   If the scans are all clear sometimes we will simply decide to wait another 3 months and repeat the PSA and maybe the scans.

Strategies if there is a Cancer Recurrence

This may sounds odd to you.  How much strategy is needed if the cancer comes back?

Based on the scan and biopsy results, the cancer recurrence can be grouped into 4 possible situations, and the treatment will depend on the situation.

1. Biochemical Failure. The PSA is abnormal but the scans are clear, and the biopsy is negative (if done), and we don’t know where the cancer is coming back.
2. Distant Failure. The cancer has come back in the lymph nodes or bones.
3. Pure Local Failure. The cancer has come back in the prostate gland or tissues that surround the prostate gland.  It is nowhere else in the body.  Scans are clear.
4. Mixed Local + Distant Failure. The cancer has come back in the prostate or prostate area, as well as in the lymph nodes or bones.

Biochemical Failures are very frustrating to patients.   We know the cancer is coming back because of the high PSA but we don’t know where, so it is hard to know what to do.  When there is a Biochemical Failure, one of my most common strategies is to just wait and watch.  I recommend repeating the PSA every 3 months, and repeating the scans every 3 – 6 months.  I then start hormonal therapy once the scans show cancer in the bones or lymph nodes, or once the PSA hits some threshold such as a value of 10.   Waiting and watching is also helpful because sometime a rising PSA can just be a “bounce” and the cancer might not be recurring after all, and it can be beneficial to give the PSA a chance to come down on its own.  Often the doctor has a hunch about whether the cancer recurrence is within the prostate gland, versus distantly in the nodes or bones.  For example, if the PSA is rising more rapidly, doubling every 3 – 6 months, then the recurrence will tend to be in the bones or lymph nodes.  If the PSA is doubling more slowly, such as every 12 – 60 months, then it will tend to be a recurrence within the prostate gland.  If the patient is still relatively young and healthy and I think the cancer could be recurring in the prostate gland then I will recommend that a prostate biopsy be done.

When there is a Distant Failure in the lymph nodes or bones, then in most cases the cancer is incurable.  The goal becomes to slow down and control the cancer, put it into remission.  We do this by starting hormonal therapy for example with Lupron injections.  In some cases there may only be 1 – 3 cancer spots (metastases) seen on the scans.  In these cases we may occasionally try to radiate the spots to bring about remission, and may even use CyberKnife to treat these metastases.    In a study by Triggiani (PMID: 28449007) one to three recurrent tumors in the bones or nodes were treated by stereotactic radiation, and 43% of patients were cancer free two years after doing that treatment.

When there is a Pure Local Failure we have an opportunity to try to cure the cancer again.  This is called “salvage therapy”.  However, salvage therapies have a lower chance of success and a higher chance of side effects than treatment the first time around, so salvage should be considered carefully.   The doctor and patient must ask “What are the odds that this cancer can still be cured with salvage therapy?   Is the patient still relatively young and healthy?   Do the possible side effects outweigh the possible advantages?”  Usually cryotherapy is the best way (in my opinion) to be try to salvage a CyberKnife recurrence in the prostate gland.   Other options are to do active surveillance (watch and wait) or to do intermittent hormonal therapy.

When there is a Mixed Local + Distant Failure this is treated the same way as a Distant Failure.   There is absolutely no advantage to doing further treatment on the prostate gland if the cancer has already escaped to other areas of there body.  That horse has left the barn.

Can I Still Have Surgery if the CyberKnife Fails?

One of the most common questions I hear is “What happens if the cancer comes back?”  Often this is accompanied by “My surgeon told me that if the cancer comes back after radiation that I cannot have surgery.  But if I have surgery first and it comes back I can still have radiation.”

This worry about backup options can make treatment decisions even harder.  Instead of just focusing on what is the best treatment here and now, we also become concerned about what the best sequence of treatments should be, in order to have options if the first treatment doesn’t work.  I get it.  Everybody wants to know that there are backup options available.  But if there is one take home message I want you to know it is this: this is a mis-leading sales pitch from the surgeons who are trying to promote surgery.   It is misleading for the following reasons:

1. CyberKnife has a very high cure rate. There are not many recurrences in the prostate gland.
2. Prostate cancer can recur in the prostate gland, in the tissues around the prostate, in lymph nodes, or in bones. It is only for cancer recurrences within the prostate gland and nowhere else in the body that this issue comes up about what treatment  to the prostate gland should be done next.
3. CyberKnife does such a great job at killing the cancer in the prostate gland that only a few CyberKnife recurrences are found in the prostate gland only. Odds of this happening are perhaps 2% of early stage cases treated with CyberKnife.
4. If the cancer does come back in the prostate gland after CyberKnife there are treatment options such as cryotherapy that are available.
5. It is true that surgery after CyberKnife is not advisable, but frankly that doesn’t matter if the chance of recurrence is low and there are other treatments such as cryotherapy that can be done.

Another common question is so why can’t surgery be done?  It is because CyberKnife causes scarring / fibrosis in the prostate gland and tissue directly around the prostate.  The surgeon can’t separate the prostate from the surrounding tissues, they are fused together.  There is a higher risk of damaging the bladder, rectum, or sphincters (urine valves) if you try to remove it surgical.

Options if the Cancer Returns in the Prostate Gland

Lets say your PSA has risen abnormally, CT and bone scans are all clear, and we perform a prostate biopsy that shows there is a cancer recurrence in the prostate.  This is what is known as a pure local failure.  This is a situation that can keep men awake at night who are contemplating treatment for their prostate cancer, wondering “what can I do next if the first treatment fails?”

These are some of the options:

1. Active surveillance
2. Hormonal therapy.
3. Cryotherapy
4. High intensity focused ultrasound (HIFU)
5. Surgical removal

Cryotherapy, HIFU, and surgery are examples of “salvage” which is a second attempt at cure.  Salvage tends to have a higher chance of side effects compared with the first treatment.  Salvage should only be undertaken in men who are healthy and have a reasonable chance of cure.   It should be avoided in high-risk prostate cancer.  The PSA should be less than 10 at the time of salvage, and the cancer should be confined within the prostate gland.

A Warning First

I have seen some cases where the PSA has risen after conventional radiation, and the surgeon has then gone ahead and surgically removed the prostate gland without first biopsying the prostate.  This is bad!  Very bad!  There may be no cancer found in the prostate in some of those cases, and the surgery is for nothing!   Always insist on a prostate biopsy showing there is recurrent cancer in the prostate before embarking on a serious salvage treatment such as cryotherapy or surgery.

On the other hand it is perfectly okay (and even preferable) to go on surveillance or hormone therapy without first obtaining a prostate biopsy.

Surveillance

This is a good option for men who are older or have other serious health conditions.  Typically, we would monitor the PSA and then we would start hormonal therapy once the PSA hits a certain threshold (such as 10) or if periodic rescanning shows that cancer has spread to the lymph nodes or bones.

Hormonal Therapy

This does not cure the cancer, but it can drive the PSA back down to 0, put the cancer back into remission and help stop it from spreading.  I would recommend hormonal therapy if the PSA is rising quite rapidly, or if the cancer is high-risk.  The hormone therapy can be given continuously / forever, or it can be given intermittently which means going on it for a while, then off it for a while.  I like using intermittent therapy for pure local failures and for biochemical failures.  Typically I would have patients go on Lupron for 12 months, and if the PSA is very low (0.2 or less) at that point they would go on a break off the medicine.  We would monitor the PSA and then restart the hormonal therapy once it rose back significantly (somewhere in the 2 – 10 range).   This way you can have breaks from the side effects of the medicine.  Note, if there is a distant failure in bones then continuous hormone therapy without a break is recommended.

Cryotherapy

I think cryotherapy can be a good treatment option when there is a pure local failure.  Typically the doctor will do a mapping biopsy, which is a detailed biopsy of many regions throughout the prostate gland to be able to generate a “map” of where the cancer has recurred.  He will then freeze those areas.  It is important to go to a doctor who has a lot of experience with cryotherapy, as there is a learning curve, and there can be complications if it is not done well.   A study by Ismail (PMID: 17662081) describes his results in 100 patients who had cryotherapy after failing conventional radiation.  At the 5 year mark, the number who were cancer free after salvage was 73% for low-risk, 45% for intermediate-risk, and only 11% for high-risk.  Incontinence occurred in 11% and erectile dysfunction in 86%.

HIFU

High intensity focused ultrasound will heat up areas of the prostate gland and kill the cancer that way.  The principles are the same as for Cryotherapy.  There are fewer reports about using HIFU after radiation failure.  Chalasan reviewed various reports and found an effectiveness of 17 – 57%, rectal fistula in 0 – 16%, and incontinence in 10 – 50%.  A rectal fistula is a very serious complication, and is a hole going from the urine passage into the rectum, and it usually requires a colostomy bag be placed.

Surgery

I don’t have too much experience with this, but some surgeons may be willing to remove a prostate gland after CyberKnife.  Although some surgeons will do prostate removal after conventional radiation failure, there may be more scar tissue after stereotactic radiation, so it may be riskier.  There may be problems with urinary incontinence afterwards, and there will almost certainly be erectile dysfunction.

 

Additional Radiation

This is not advised.  There is permanent scarring after a treatment course of radiation, and adding a second course will just create more scarring and side effects.  Also, CyberKnife is a very powerful treatment.  If CyberKnife did not work the first time then why should a second course of any type of radiation work?  When there is a recurrence it is like you are starting at the beginning, you cannot just give a little more radiation to try to cure it.  You need to give even more intensive treatment than you did the first time around.   Not feasible.   Even doing creative approaches such as hyperthermia + hormone therapy + conventional radiation seems like a risky idea to me.

What Happens if Salvage Treatment Doesn’t Work

You may be wondering about this, especially since salvage treatments can be unsuccessful.  Prostate cancer salvage treatment should only be done once in my opinion, there should almost never be a third attempt at cure.  The risk/benefit ratio would be off the charts for a third attempt.  It is preferable to do surveillance or hormonal therapy in those cases.   Perhaps there are a few exceptions where just part of the prostate gland is frozen with the first recurrence, and a different part of the prostate gland is frozen with the second recurrence.

When Should a Repeat Biopsy be Done?

Any test should only be done if the results can change what we do.    We do not want to put men through the discomfort of another biopsy unless the results might change our treatment recommendations!

If the PSA shows there is a possible or likely treatment failure we first start with CT scans and a bone scan.

If these scans show cancer elsewhere in the body, then A) we have an explanation for the rising PSA, and B) the cancer is no longer curable and the treatment will be typically be hormonal therapy.  There is no need for another prostate biopsy.

If the scans are clear, then we must ask ourselves this simple question:

If I do a prostate biopsy that shows there is recurrent cancer in the prostate, will I then recommend a salvage treatment such as Cryotherapy?

YES – if the patient is relatively young and healthy, the prostate cancer was not high-risk to begin with, the PSA is less than 10, and the PSA is not rising very rapidly.

NO – most other cases.

Example 1

55 year old pilot had a Gleason 9 prostate cancer in 9/12 cores, PSA 18.  He is treated with hormonal therapy, CyberKnife, and IMRT to the entire pelvis.  His PSA drops to 0.05 on treatment.  However, one year after he goes off of the hormonal therapy, his PSA has risen to 5.   His scans are clear at that time.  Should I order a biopsy?   Answer: NO.  He has high-risk prostate cancer.  Even thought the scans are clear there is a high chance that he has cancer cells already present in the bones or nodes, they are just not big enough yet to show up on scans.   His PSA also rose quite rapidly over 1 year.  The odds of curing him with salvage therapy like cryotherapy is very low.   Treatment recommendation would be hormonal therapy.

Example 2

A healthy 65yo had a Gleason 7 prostate cancer, PSA 12.  He is treated with CyberKnife alone.   PSA drops down to 2.5 by the 1 year mark, but at 2 years it has risen and is now up to 4.6.  Scans are clear.  Should I order a biopsy?  YES.  He has intermediate-risk prostate cancer, his PSA is not rising ultra-rapidly, and it is plausible that the cancer has come back only in the prostate gland.   I do the biopsy and it is negative.  We decide to keep monitoring the cancer every 3 months for now, and maybe we will repeat the biopsy again later on if the PSA rises more.  On the other hand maybe this is just a bounce and the PSA will drop back down on its own.