Cancer Recurrence After Radiation

CHANCE OF RECURRENCE
When we talk about a 90% cure rate for stage 1 prostate cancer, that means there is a 10% chance of cancer recurrence, that it will come back sometime during an average patient’s remaining lifetime. Stage 2 has a 20% chance of recurrence, and stage 3 has a 30 – 40% chance of recurrence. Even in cases of recurrence, prostate cancer is still typically a slow-motion cancer which can often be managed for many years. There are no randomized studies showing that doing a second attempt at cure will make you live longer than just doing surveillance or hormone therapy (ADT).

A RISING PSA IS THE FIRST SIGN OF A PROBLEM
The way we first detect cancer recurrence is by a rising PSA. No matter where the prostate cancer is coming back in the body – prostate, lymph nodes, or bones – a rising PSA will be the first sign of a problem in 99% of patients. PSA is like a barometer. It is the first warning sign before scans show a problem or there are any symptoms.

PSA’s tend to bounce up and down after radiation, so we look for a definite rising trend. If the PSA has risen more than 2.0 points above the post-treatment minimum, this is the official definition of a radiation therapy treatment failure. Example: A patient has a PSA of 6.0 and undergoes radiation. His PSA gradually drops down to 1.0 over two years. Then it begins to rise and is now up to 3.5. Because it has climbed more than 2 points since the minimum value following treatment, he is now classified as a radiation treatment failure, also known as a biochemical failure. Note than if a patient has already undergone both surgery and then radiation, then pretty much any amount of subsequent PSA rise is abnormal.

BEWARE OF THE BOUNCE
Occasionally someone can be incorrectly classified as a radiation treatment failure. There is something called a “PSA bounce” where the PSA jumps up, then levels out, then drops back down over a period of several months, all on its own. This typically occurs within 1 – 3 years after radiation treatment. Sometimes patients are told that their cancer has come back, but then the PSA spontaneously drops back down to less than 1.0 all on its own. Be patient if the PSA is rising.

TESTING
If we are worried that there is a radiation treatment failure, the next step is to do testing. The cancer might be coming back in the prostate gland, in the tissues that surround the prostate gland such as the seminal vesicles, in pelvic lymph nodes, in other lymph nodes in the body, in the bones, or very rarely in other organs like the liver or lung. The most basic tests are to start with a CT scan and a bone scan. If these don’t show the cancer, then there are more sensitive scans such as the Axumin-PET scan or the PSMA-PET scan. A repeat biopsy of the prostate gland is typically only considered if the scans are all clear.

Testing can often be unreliable to determine where the recurrence is. Biopsies can miss the cancer (False Negative). It takes a while for all the cancer cells to vanish from the prostate after radiation, so in the first two years after radiation biopsies can sometimes still pick up lingering cancer cells, even though that cancer is destined to disappear and it is not a true reading (False Positive). Scans can only pick up cancer once the tumor(s) reach a certain size. If the PSA is less than 0.5, even the most sensitive scans like a PSMA PET scan are likely to not show the cancer. In addition, scans occasionally show areas that look like they could be metastases, such a hotspot on a rib in a bonescan, but they may just be benign finding like an old rib fracture.

Often when there is a cancer recurrence, we have to make assumptions about where the cancer is coming back. Sometimes there are clues. A rapidly rising PSA which is doubling every 6 months or faster has a higher chance of being from metastatic cancer that has spread to the nodes or bones. If the cancer was already present in the nodes before radiation started than there is a higher chance that it is a metastatic recurrence. If the cancer was a very high Gleason score (8 – 10), then there is a higher chance it is a metastatic recurrence.

THE FOUR SCENARIOS AND TREATMENT OPTIONS
Depending on the results of the scans and biopsy we have the following four scenarios:
1) Metastatic Recurrence in the bones and/or nodes. In addition the recurrence may also be present in the prostate gland simultaneously, but this will not change your options. Treatment is usually androgen deprivation therapy (ADT / Lupron).
2) Very limited metastatic recurrence in the bones and/or lymph nodes, in only 1 – 3 discrete spots. This is called an Oligometastatic Recurrence. Treatment can be either androgen deprivation therapy (ADT) and/or spot radiation directed to the metastases which is called stereotactic body radiation therapy (SBRT).
3) In an Isolated Local Recurrence, cancer has come back in the prostate gland or in the tissues surrounding the prostate gland, but is not found elsewhere in the body. Treatment options can include continued surveillance (doing nothing), salvage cryotherapy, salvage HIFU, salvage surgery, continuous androgen deprivation, or intermittent androgen deprivation.
4) Cancer has not yet been found anywhere, despite PSA indicating a treatment failure. This is called a Biochemical Recurrence. Treatment options can include continued surveillance with regular PSA’s and scans, continuous androgen deprivation, or intermittent androgen deprivation.

SALVAGE THERAPY
A major concern of prostate cancer patients is what can be done next if there is a treatment failure, in other words is there a backup option to try to cure the cancer. I grew up in Canada, where the saying “kick at the cat” means an attempt to do something, in this case an attempt to cure the cancer. Salvage is a “second kick at the cat”, ie a second attempt at curing the cancer.

Salvage therapy only makes sense if the cancer has recurred within the prostate gland or in the tissues immediately surrounding the prostate gland. If the cancer had already spread to the lymph nodes or bones then it is usually no longer curable. There is another common saying, “the horse has left the barn”. Once cancer has already metastasized to other parts of the body, all of those metastases can also create new metastases, and just re-treating the prostate gland is unlikely to offer much benefit at all. Which raises the question “why can’t we just target all the metastases in the body?” This is like playing the carnival game whack-a-mole. You target one spot, only to see another one or two spots quickly appear. When there is metastatic cancer there are usually a multitude of other tiny spots in the body that are too small to be picked up on scans, but which will eventually grow. There are occasional cases where the cancer has only appeared in 1 – 3 metastases, which is called oligo-metastases, i.e. “a few metastases”, and we apply targeted treatment to these few spots in the hope that this is all there is, and no other spots will pop up.

If salvage treatment was easy and safe, we would try it readily, even in cases where we were not sure it would help. However, salvage therapy is always associated with a higher risk of side effects and a lower chance of success than treatment the first time around. Giving radiation after failing surgery is reasonably safe, so we often do it if we “think” the cancer is coming back in the pelvis, but we aren’t 100% sure. However, performing salvage after a radiation treatment failure is a different situation. You should be sure the cancer is coming back in the prostate gland with a repeat biopsy, and you should be reasonably confident the cancer is not coming back elsewhere in the body.

Urologists often say that a benefit to starting with surgery is that radiation can be done after surgery, but surgery cannot be done after radiation. This is mostly true, but this is a very complex issue for which someone could write a PhD thesis. The first thing is that treatment failure in the prostate gland is not very common with modern radiation techniques. Dr. Katz did a 10-year follow-up study on his stereotactic (SBRT) stage 1 patients, and he found that the cancer came back in the prostate gland in less than 2% of the men. And if it does happen, we can still send patients for freezing (cryotherapy), heating (HIFU), or even sometimes for surgery at centers with experience in salvage surgery.

TEN RULES
A few of my rules regarding salvage therapy after a radiation treatment failure:
1) Salvage after radiation should only be done for Isolated Local Recurrences, where the cancer has been proven to come back in the prostate gland, but has not spread to the bones or lymph nodes. If cancer has already spread to the bones or nodes then “the horse has left the barn”, then it does not matter what you do the prostate gland.
2) Salvage treatment carries a greater risk of bad side effects (up to 50%) and a lower chance of success (50%) than treatment the first time around.
3) There is no “third kick at the cat”. The cat has run away and will not let you kick it a third time. If salvage fails, there is little benefit to trying yet another salvage therapy. 90% chance it won’t work, 90% chance it’ll cause life altering side effects. The treatment choices are surveillance or androgen deprivation. The exception: if the cancer comes back in one or two spots that are in an area that has not had previous radiation.
4) Do not use the same treatment for salvage that failed the first time unless there is a clear and obvious reason why it failed which can be avoided the second time around. Otherwise, why should it work the second time?
5) Because salvage carries such a high risk of side effects, there should first be a prostate biopsy proving there is recurrent cancer in the prostate gland. Beware that biopsies done within 24 months after completing radiation may sometimes falsely show there is still active cancer remaining in the prostate gland.
6) You only need to do a prostate biopsy if the scans are all clear, the cancer has never metastasized, and if salvage therapy is considered an option. Otherwise, why bother.
7) If surgery was not considered a reasonable option when the cancer was first diagnosed, then salvage treatment is likely NOT a good option if the cancer has recurred, and in fact it is probably a worse option.
8) The main salvage options after radiation treatment failure include cryotherapy, HIFU, and possibly surgery. These procedures should only be done at specialized clinics with a lot of experience performing these salvage procedures.
9) The safest treatments for Isolated Local Recurrences are to do surveillance, or to do intermittent androgen deprivation therapy (ADT). Intermittent ADT typically involves going on ADT for 12 months, getting the PSA down to zero, then stopping and only resuming the ADT if and when the PSA rises to a certain value such as 2.0 or 4.0 or 10.0. Androgen deprivation will not cure the cancer, but is can put it back into remission and slow it down.
10) The beauty of intermittent ADT is threefold: 1) it will treat recurrent cancer no matter where it is in the body. 2) if it is not a true recurrence i.e. just a PSA bounce or a falsely positive biopsy or falsely positive scan, then the PSA should drop to zero, then remain very low after the ADT is stopped. 3) there is minimal risk of serious side effects compared to salvage therapy. This is my favorite treatment when there is a radiation treatment failure.