Prostate Cancer

Treatment of Recurrent Prostate Cancer

Defining, Investigating, and Categorizing Recurrence

Of the large numbers of patients undergoing treatment for prostate cancer, there are many whose cancer will not be cured, but instead the cancer will recur at some point in the future. This can be devastating news, but there are still many options and treatments that can be done if the cancer does return. There can still be hope for cure, or remission, or at least living with the cancer and not letting it get the better of you.

This chapter deals with cancer which has recurred after a previous attempt at curing the cancer, be it with surgery, radiation, brachytherapy, cryotherapy, or other such treatment.

Defining Cancer Recurrence

If prostate cancer recurs, it can recur in the prostate gland, the tissues surrounding the prostate (fat and seminal vesicles), in the lymph nodes, or in the bones or other organs. This is known as a "local failure" for a recurrence in the prostate and surrounding prostate region, or a "systemic failure" if it recurs in the lymph nodes or bones. If the PSA is rising, this is known as a "biochemical failure". A cancer recurrence can involve any combination of these three types of failures. The PSA will rise whether the cancer recurs in the prostate gland, or in other parts of the body such as the bones. In only 1% of cases, the cancer can recur without a significant PSA rise.

Sometimes it is not as easy as it sounds to tell if a cancer has recurred. With the current accuracy of PSA tests, often the PSA is the first sign that cancer is recurring. PSA has created a whole group of patients who are diagnosed with prostate cancer because of a high PSA, despite having no symptoms, and not even having a nodule which can be felt in the prostate gland. Likewise, PSA has now created a whole group of patients who are being told that their cancer has recurred, despite having no symptoms, no abnormalities on x-rays, and often not even a nodule on the rectal exam.

In the pre-PSA era, cancer recurrence was generally diagnosed in one of two ways, and these ways are still valid:

1. Pain developed in the bones or in the pelvis, and x-rays showed that the cancer had metastasized (spread) to bones or to lymph nodes.
2. Follow-up rectal exams showed that a nodule in the prostate gland was growing larger, sometimes associated with worsening urination symptoms. A repeat biopsy of the prostate would often then be done, and would show recurrent cancer.

Now with PSA, life has definitely gotten more complex for the cancer patient and his doctor. After prostatectomy or cryosurgery, treatments which remove or destroy the prostate gland respectively, the PSA should drop down to very low levels, usually less than 0.2 . This is significantly lower than the normal value for people without prostate cancer, which is less than 4.0. For patients who undergo radiation or brachytherapy, the PSA should drop down to a low value, but not quite zero, which reflects the fact that the cancer is gone but that there may be some healthy prostate cells surviving which still produce PSA. A commonly quoted value is that the PSA should drop down to less than 1.0 after radiation or brachytherapy. A simple way to define recurrent cancer then, is if the PSA is greater than 0.20 after radical prostatectomy, or greater or equal to 1.00 after radiation or brachytherapy. But, it turns out that this isn't always correct. After radiation or brachytherapy, sometimes the PSA may "bounce" around a bit, that is, go up and down, even though there is no recurrence of the cancer.

The American Society for Therapeutic Radiation Oncology (ASTRO) came up with a consensus definition of a PSA-defined treatment failure following radiation treatment. Their definition of a biochemical (PSA) failure was if the PSA rises on three successive measurements, with each measurement taken at least 3 months apart. Even this definition has some drawbacks though. Not infrequently if someone has been on hormone therapy and radiation, once the hormone therapy is stopped the PSA may rise slightly as the testosterone levels in the body increase. For example, the PSA may rise from 0.10 to 0.15, 0.20, and then stabilize at 0.25. This would be labeled as a biochemical failure under this definition, even though a PSA of 0.25 is very good following radiation. ASTRO has redefined its definition of PSA failure as being when the PSA rises 2.0 points above the minimum PSA obtained since treatment. Another problems with both these failure definitions is the concept a "benign PSA bounce", described by Kent Wallner, MD, which can occur following a prostate permanent seed or HDR implant. Sometimes following a seed implant, the PSA may rise as high as 6.0 or even more, and then fall back down to less than 1.0.

The bottom line is that if the only sign of failure is a PSA failure, there should be thorough testing to see if there is any other proof that the cancer has recurred. With no other evidence, it may be best to watch the PSA for a while to verify that there is a definite rising trend, especially if the PSA value is still quite low. Be skeptical!

Investigating a Cancer Recurrence

If a cancer recurrence is known or suspected, it is wise to do testing to see where the cancer has recurred. Especially if further treatment is planned, it is important to be confident that the cancer has recurred, and to know exactly where that recurrence is. If someone has a persistently rising PSA and has a "biochemical failure", this means that cancer is returning in at least one of the following body tissues:

The most common areas for cancer to recur is in the prostate gland, prostate region, pelvic or abdominal lymph glands, or bone. Cancer can recur in any combination of these tissues. Sometimes in patients with biochemical failure cancer cannot be seen in any of these areas, despite thorough scanning and even biopsies.

The most basic tests are a PSA blood test, a rectal exam, and a bonescan. The bonescan can identify if any new abnormalities are seen in the bones, which could indicate that the cancer has spread to the bones. If the rectal exam is worsening in conjunction with a rising PSA, this indicates a likely "local failure" in the prostate region.

A CT scan or MRI scan of the abdomen and pelvis can be useful to see if there are enlarged lymph glands (which may contain cancer) or to see if the tissues surrounding the prostate gland look abnormal.

A Prostascint scan can show clusters of prostate cancer cells. After a prostatectomy, if a prostascint scan shows uptake in the tissues around where the prostate used to be, this can mean a local recurrence. The Prostascint is also very good at showing abnormal uptake in lymph nodes. Overall, it is more accurate than a CT scan, but more expensive and much more time consuming for the patient.

PET scans may not show prostate cancer, and are only occasionally used for prostate cancer patients.

Usually, a repeat biopsy is not needed when there is clearly a systemic cancer recurrence. However, in cases where the PSA is rising but all the scans are normal, or in cases where re-treatment of the prostate gland is being considered, it is often wise to repeat a biopsy of the prostate or its surrounding tissues. A standard ultrasound guided needle biopsy is done. One warning: a prostate biopsy done within 1 - 2 years following radiation or brachytherapy may still show cancer cells which are in fact dying, and so the results may not be accurate. Biopsies done more than 24 months following radiation are usually accurate.

Categorizing and Managing Prostate Cancer Recurrences

As have been mentioned, there are there main types of failures following previous treatment: biochemical, local, and systemic. A patient can have any of the six combinations of these three failures. For management purposes though, treatment failures are best lumped into three categories:

1. Pure biochemical failure
   • PSA is following a rising trend, and/or has surpassed a threshold value such as 1.00 post-radiation or 0.20 post-prostatectomy.
   • No areas of local or systemic failure have yet been found on scanning or biopsy.
2. Pure local failure
   • Recurrence in the prostate gland or surrounding tissues
   • Usually the PSA is elevated, but does not need to be
   • No systemic failure has been found on scanning.
3. Systemic Failure (+/- local failure)
   • Recurrence in the lymph nodes, bones, or other organs
   • Usually the PSA is also elevated

Managing Systemic Failure

Prostate cancer which has recurred in the lymph nodes, bones, or other organs is no longer curable. However, it is still treatable, it can be put into remission, and there is still a good chance of living a normal life. We usually need to rely on treatments which affect the entire body, like hormone therapy.

Treatment of a systemic failure is handled the same way as for a patient who presents initially with metastatic cancer.

Managing Pure Local and Biochemical Failures

A pure biochemical failure creates a dilemma. A relentlessly rising PSA means that there is active cancer somewhere in the body. The question is, is the cancer coming back locally in the prostate region or systemically in the body? A local recurrence can still sometimes be treated again for cure, known as salvage therapy. A systemic recurrence means that the cancer is incurable, but can still be put into remission with hormone therapy. Some physicians tend to assume a rising PSA is coming from the prostate gland region if the scans are all normal, and they may even proceed with salvage therapy without doing a confirmatory prostate biopsy. However, there may be small amounts of cancer in the lymph nodes or bones which are not picked up on scans. It can be a leap of faith to assume that the PSA is coming only from the prostate area.

Even so-called local failures may be systemic, despite a normal bonescan and CT scan. All the factors must be considered, like PSA, stage, and the pathology report, to come up with your own gut feeling whether the recurrence may be systemic in addition to local.

Deciding where the PSA is coming from: is it a local failure or a distant failure?

In the event of normal scans, here are some guidelines which can help indicate whether the recurrence is more or less likely to be systemic:

(*) PSA Doubling Time (DT) is the length of time, in months, it takes for the PSA to double in value. For example if on April 1^st the PSA was 3.6, and on November 1^st the PSA was 7.2, the doubling time would be 7 months.

The formula for calculating DT on a calculator is: DT = (date2 - date1)/30.5 * log(2) / log (PSA2 / PSA1) , where PSA1 is the PSA value done on date1, and PSA2 is the PSA value done on a future date, date2. Date2-date1 is the difference in days between the two dates. Preferably use two dates which are separated by at least 2 months.

Your Treatment Options for Localized or Biochemical Recurrences

If, after your assessment, you feel that your cancer has a reasonable chance of being purely localized, salvage therapy may be a good option for you. If you are worried that there may be some early systemic failure also going on, or if you do not like the idea of salvage therapy, other options can include observation (watchful waiting), starting hormone therapy, or experimental treatment. These options will all be discussed.

Hormonal Therapy for Local or Biochemical Failures

Hormonal therapy is the most common treatment used after failure of radiation. It is a relatively low toxicity treatment, and will not cause further incontinence or tissue damage. It is a good option for many patients. However, it offers no hope for cure, only the hope that it will keep the cancer in remission until the patient dies of another illness. Schellhammer analyzed the results of hormonal therapy after pure local failure in 57 external beam failure patients and 14 permanent seed failures. The cancer specific average survival duration was only 5.8 years and 7.3 years for the two groups.

Hormonal therapy is the most widely recommended treatment for patients who develop a pure local failure after external radiation or permanent seed implantation. For many patients however, this is not a comfortable decision. Some are willing to risk the possible complications of aggressive therapy in order to have a reasonable chance of curing the cancer. Others wish to avoid the possible side effects and unproven benefits both salvage and hormone therapy and prefer to go on a watchful waiting program.

Watchful Waiting & Natural Therapy for Local or Biochemical Failures

This can be an excellent option. I feel that many people are being put needlessly on hormone therapy, which has many side effects. There has been a study that shows that if you start hormone therapy right away in patients with early bone metastases (less than 5 spots), rather than wait until they have symptoms, that you can prolong their survival time. Also, in the Bolla study, patients with pelvic lymph node metastases who were put on 3 years of hormonal therapy right away (along with pelvic irradiation) had a longer survival than those who did not.

Some physicians extrapolate and say that local or biochemical failure is like very early metastatic cancer, and therefore survival time should be extended if hormone therapy is started as soon as possible. However, there is currently little evidence that early hormone therapy for these early local and biochemical failures will prolong survival. We do know that hormonal therapy can cause hot flashes, increased fat, reduced muscle, reduced bone density (osteoporosis), loss of sex drive, impotence, fatigue, breast growth and tenderness, and possibly increased cardiac deaths.

For this reason, I feel that it can be a good option is to go on an intelligent watchful waiting program, which means watchful waiting with some modifications. The elements of this program are:

Intelligent Watchful Waiting (IWW) for Local Failures and Biochemical Failures

Experimental therapies for local and biochemical failures

I think this can be a very good option, especially where the experimental therapy appears to have a much lesser risk of side effects than salvage prostatectomy or salvage cryotherapy. Gene therapy is an example. Viruses containing a gene to control the cancer are injected into the prostate gland. Viral and Vaccine experimental therapies like Provenge™ are usually reserved for patients who have failed hormonal therapy. Dietary, supplements, and/or lifestyle modification studies are being performed at some hospitals for patients with local recurrences. Some trials are comparing hormone therapy to no-hormone therapy.

Salvage Therapy

Concepts of Salvage Therapy

Salvage means to try to cure a cancer which has relapsed after an earlier attempt at cure. In other words, it is the proverbial second kick at the cat. Salvage therapy is only an option if the cancer has recurred in the prostate gland or its surrounding tissues. There cannot be any cancer systemically in the bones, or in the lymph nodes, otherwise salvage will be unsuccessful.

Usually a treatment method different from the first treatment is used. After all, why repeat a treatment which failed the first time around? Often with recurrences we are dealing with a more aggressive cancer than average. The fact that it recurred makes it more aggressive than cancers which do not recur. Also, we are often dealing with body tissues which are now scarred by surgery or radiation. As a result, I have a rule regarding salvage therapy:

You'll see that this is true when I describe the results of various salvage studies which have been published. Using salvage prostatectomy and salvage cryotherapy following radiation failure has a success rate of around 25% and an incontinence rate of around 50%.

If some people have doubts about using conventional treatment for localized prostate cancer, those doubts are only amplified if they consider salvage therapy! This is why, even though in Tulsa I developed a clinical research protocol in 1998 to use HDR brachytherapy to treat radiation and permanent seed failures, I have been very cautious in recommending it. While I think salvage can be an option, it needs to be considered much more carefully than does treatment the first time around.

I believe it is very important to have complete scans done before salvage therapy is considered, to ensure there is no spread of cancer to other areas of the body. At minimum, a bone scan and a CT or MRI scan should be done. A prostascint is also a good option.

I am of the opinion that a prostate (region) biopsy proving there is recurrent cancer is very important. There is too much at risk with salvage therapy to just treat on a hunch that the cancer is the prostate region.

Sometimes radiation is recommended a short while after a prostatectomy, because of findings on the pathology report. I don't feel a biopsy is needed in those cases, because this isn't really salvage therapy; it's treatment based on the belief that small microscopic amounts of cancer may have been left behind. This is also known as adjuvant therapy. However, in cases where the PSA rises many months after a prostatectomy, it is still a good idea to consider doing a trans-rectal ultrasound and biopsy the tissues in the area where the prostate was removed, especially in the area where the urethra (urine passage) was re-connected.

Salvage After Local Failure of Radical Prostatectomy

Many patients do not readily understand how prostate cancer can recur in the prostate region after a prostatectomy. After all, if the prostate is removed how can the cancer come back? In an Oklahoma review of medicare patients undergoing prostatectomy, it was found that 41% of the patients had positive margins. This means is that cancer went right to the edge of the tissue that was removed, and therefore some cancer cells were left behind in the body. These cells will start to multiply, and can form a cancer recurrence in the prostate bed, i.e. in those tissues which formally surrounded the prostate gland. The junction where the urethra is reconnected is a frequent site of recurrence. Also, in the surgeon's effort to preserve the erectile nerves or to preserve the urinary sphincter, prostate cancer cells may be left behind. Even without positive margins, local recurrences can still occur. Factors that increase the chance of local recurrence include the cancer grade, pre-surgery PSA value, size of the cancer, number of positive biopsy cores, cancer in the seminal vesicles, cancer infiltrating the prostatic nerves, and cancer invading the capsule. After radical prostatectomy, the PSA should drop below 0.2. Any rise in PSA above 0.2 usually indicates recurrent or persistent prostate cancer.

External beam irradiation alone has commonly been used as a salvage therapy after prostatectomy, generally with reasonable side effects. Rarely, brachytherapy has been used in conjunction with external beam irradiation for these salvages, but there is usually not enough tissue in the area to do a good brachytherapy implant.

Salvage After Local Failure of Cryotherapy

Very little, or nothing, has been published about how to salvage a cryotherapy failure. External beam irradiation would probably be a good choice. As well, after cryotherapy, there can be a small amount of prostate tissue left, which can allow prostatectomy or brachytherapy to be used. The tissue may be too small for a permanent seed implant, but an HDR temporary brachytherapy implant may be feasible, in conjunction with external beam irradiation.

Salvage After Local Failure of External Radiation

Local failure of external beam radiation appears to be a relatively common problem. Recent innovations like 3D conformal radiation, intensity modulation radiation therapy, and brachytherapy have allowed radiation oncologists to treat the prostate gland to a higher dose, reducing the possibility of local failure. However, there have been many patients treated in the past with standard, conventional forms of radiation therapy, usually to a total dosage of 66 Gy. Some of these patients will develop local failures, especially those who had a large amount of cancer in the prostate gland prior to treatment.

Salvage cryotherapy for external beam failures

The concept of using cryotherapy to treat prostate cancer recurrences is very attractive. Needle probes are placed through the skin into the prostate gland, under ultrasound guidance, and the prostate gland and tumor is frozen. Usually, the urethra is kept warm during the procedure with hot water or another device, to prevent the urethra from being damaged. Unfortunately, there is still a very significant risk of side effects. Also, if any cancer cells are present in tissues beyond the confines of the prostate gland, this treatment may be unsuccessful.

Cespedes described his complication rates for 143 patients who underwent salvage cryosurgery after failing external beam radiation. Depending on which urethral warmer he used, permanent incontinence ranged from 28 to 42%, and urinary obstruction occurred in 14 - 54%.

Pisters reported on cryosurgery salvage for 150 patients, who failed external beam. Biochemical (PSA) control was achieved in only 31%, but urinary incontinence occurred in 73%, urinary blockage symptoms in 67%, impotence in 72%, and severe persistent pain in 8%.

Some doctors with a lot of cryotherapy salvage experience include Dr. Bahn and Dr. Fred Lee, Jr.

Salvage surgery for external beam failures

Surgery for recurrent prostate cancer can involve removing the prostate gland (salvage prostatectomy), removing the prostate plus bladder (salvage cystoprostatectomy), or in the most extreme cases removing the prostate, bladder, and rectum (pelvic exenteration). Removing the bladder requires that the urine be channeled to an opening on the abdomen, where a bag is placed to collect the urine. Removing the rectum requires that the colon be channeled to a colostomy opening on the abdomen, where a bag is used to collect the stools.

Not all urologists will perform salvage surgery after previous radiation or brachytherapy. It is a more specialized procedure. There can be scar tissue in the area which can make the resection more difficult. Sparing the erectile nerves is virtually impossible, and the urinary sphincter may be damaged during the procedure.

Rogers reviewed their experience with salvage prostatectomy in 40 patients. Urinary incontinence was permanent in 58%. 15% developed rectal injuries, and 2 patients required a temporary colostomy. 54% were found to have cancer invasion into the seminal vesicles or lymph node metastases on pathology.

Pontes has a series of 43 patients who underwent salvage surgery: 35 had radical prostatectomies and 8 underwent radical cystoprostatectomies. 9% had resultant rectal injuries, 30% developed incontinence (not including the 8 patients who now have their urine diverted to a bag on their abdomen), 70% had positive surgical margins, and only 23% were cancer-free biochemically at 1 - 10 years follow-up. The patients who had "positive surgical margins" indicates that cancer went right to the edge of the tissue removed by the surgeon, implying cancer was left behind in the body. Despite these results, the authors stated conclusion was that "salvage surgery has a place in the treatment of prostate cancer after radiation therapy failure."

In Moul's series, 22 patients underwent salvage surgery (prostatectomy, cystoprostatectomy, or exenteration). Only 27% had disease contained within the pathologic specimen. 23% at their most recent follow-up had no evidence of cancer. All 12 prostatectomy patients are continent. Complications were substantial in the cystoprostatectomy / extenteration group, with 50% having major complications.

Salvage brachytherapy for external beam failures

Brachytherapy may be used for salvage after failure of external beam irradiation. This is a somewhat experimental use of brachytherapy offered in a few centers, and no results have been published. Permanent seed implants, LDR temporary brachytherapy and HDR temporary brachytherapy have been used. Brachytherapy offers the possible advantage of causing less incontinence and other side effects then salvage cryotherapy and surgery. Salvage brachytherapy will cause impotence, and can potentially cause incontinence. It may also possibly cause chronic pain, and damage to the rectum.

We have used HDR brachytherapy at CTCA to salvage external beam failures. This has involved giving two separate HDR implants separated by a couple weeks. More dosage is given to the region of the prostate gland where the recurrence in suspected to be. Brachytherapy catheters can be placed up into the seminal vesicles and can reach areas of possible extracapsular extension.

Salvage After Local Failure of Brachytherapy

Modern permanent seed implants have allowed the dosage to be pushed much higher, to as high as 160 Gy for iodine seed implants, versus 66 Gy for conventional external beam irradiation. However, since the radiation is released so slowly, this is biologically equal to only about half of 160. The results reported by the Seattle team have been very good. What is happening now however, is that hundreds of small cancer centers have started doing seed implants, with incredible variability in quality. The smaller, or less successful centers are not publishing their results. As a result, in the future I think we will be seeing many more local failures than would be expected by the Seattle data, and these patients will be struggling to find ways to deal with this.

Brenner reported on Memorial Sloan Kettering's experience of the use of salvage prostatectomy after failure of Iodine-125 permanent seed implantation. A "highly selected group" of 10 patients underwent salvage. Only 3/10 were found to have organ confined disease on pathology. In total, 3/10 are disease free at an average follow-up of only 30 months. They comment that "Salvage radical prostatectomy... should not be widely advocated as an effective treatment option for patients with locally recurrent prostate cancer after 125-I implantation."

The studies which were previously described about using prostatectomy and cryotherapy to salvage external beam would likely apply to permanent seed implant failures as well.

Salvage HDR brachytherapy + external beam after failure of permanent seed implant

Use brachytherapy to salvage a brachytherapy failure? CTCA has been using a protocol to do this since early 1998. Similar to how we treat untreated patients, an HDR implant is given and is followed a couple weeks later by moderate dose (45 Gy) conformal external beam irradiation. We also use short-term hormonal therapy for 3 months before the implant and three months afterwards. External beam in this moderate dosage is usually well tolerated because the bladder and the rectum did not receive much radiation previously from the seed implant. There are some reasons why this three-pronged treatment approach may be expected to work:

1. Local recurrences after a permanent seed implant are often in regions of the prostate which were not adequately covered by permanent seeds, for instance up high in the prostate base. HDR catheters excel in covering hard to reach areas like the base, seminal vesicles, and extra-capsular tissues.
2. The radiobiology of HDR and even external beam is quite different from permanent seed radiobiology. Tumor cells which are resistant to the slow trickle release of radiation from iodine seeds may respond to the intense radiation exposure from an HDR treatment. There is an Australian study which suggests prostate cancer cells should be more responsive to HDR than other forms of radiation.
3. With HDR, we can "sculpt the dose" and give more radiation to the areas of the prostate with suspected cancer recurrence.
4. We know from salvage prostatectomy studies that local recurrences often have cancer cells extending into the extra-capsular tissues and seminal vesicles. Both HDR and external beam will treat these surrounding tissues. Other salvage therapies will often miss these areas.
5. By combining two different treatments given in moderate dosages each, HDR and external beam, we may be able to avoid some of the side effects seen with high dose external beam alone, or high dose brachytherapy alone. Combining different treatments can result in a lessening of the overall side effects if they have different side effect profiles.
6. Hormone therapy is known to improve the results of radiation in high-risk and bulky prostate cancer. Recurrent prostate cancer is, in my opinion, high risk by definition. Many or most of these local failure patients did not receive hormone therapy with their initial seed implant.

Case Histories

A Permanent Seed Failure Salvaged by HDR + External Beam (HM)

Mr. M was diagnosed with prostate cancer in 1992. At that time his PSA was 17 and his Gleason score was 6. He underwent an Iodine-125 radioactive seed implant in December 1992 at a major center, and had 70 seeds injected. His PSA declined down to a minimum value (nadir) of 1.3 in February 1994.

The PSA subsequently began to rise. By February 1996 the PSA was 5.0, and by October 1997 the PSA was up to 12.6. His DRE revealed some firmness on both sides of the gland. A repeat biopsy was done in August 1997, and this showed recurrent Gleason 6 cancer in the left side. A bone scan and CT scan of the pelvis were done and were normal. A prostate ultrasound showed a suspicious area in the periphery of the left lobe of the prostate gland, up towards the base. This area was not well covered by permanent seeds.

We discussed the various treatment options, but decided to use salvage HDR brachytherapy with external beam irradiation. He was started on Lupron hormonal therapy. After three months of this, we did an HDR temporary brachytherapy implant in January 1998. This was followed by 4 ½ weeks of external beam irradiation. The hormone therapy was stopped in April 1998. The accompanying photo shows permanent seeds (bright white spots) surrounding the urethra in the middle. The more peripheral black spots are the HDR brachytherapy catheters which were used for salvage.

Following treatment, his PSA dropped down to 0.1 and has remained at this level through his most recent visit in September 1999. The urination is currently very good, with a low AUA urinary symptom score of 7 out of 35. He initially had complete urine control, and no problems with the rectum. With passing time however, he developed some narrowing (stricture) of the urethra.

Summary

Prostate cancer recurrence can occur after any type of previous treatment. Cancer can recur in the prostate gland, the surrounding tissues, lymph glands, bones, or other organs. It is important to know if the recurrence is in the prostate gland and surrounding tissues only (local failure), or if it is in other parts of the body (systemic failure). Sometimes, only the PSA is elevated, and it cannot be determined whether the recurrence is local or systemic.

A local failure can be retreated for a second chance at cure, also known as salvage. Salvage treatment is generally less successful and has a greater chance of side effects than the initial treatment, and should not be considered lightly. Other options for local failures and PSA-only failures include hormone therapy and watchful waiting (observation). Systemic failures are usually treated by starting hormonal therapy.