When PSA Doubling Time Shows a Prostate Cancer Relapse in Men

One cannot really talk intelligently about prostate cancer without a working knowledge of the PSA blood test.  Most people are familiar with using PSA to diagnose prostate cancer at an early stage. There are, however, other important uses for PSA. 

The Varied Roles of PSA

PSA plays many different roles. The most familiar is for cancer screening. It is also used for staging men who are newly-diagnosed.

  For example, men who are Low-Risk have a PSA under 10. Intermediate-Risk men have a PSA from 10 to 20. High-Risk men have PSA levels above 20. PSA can also be used to detect a cancer relapse after surgery or radiation.  Recurrent disease can behave in an indolent manner or it can be rapidly growing.  What is interesting is that the rate of PSA rise, the time it takes to double, provides deep insight into how aggressively the cancer will behave in the future.  Treatment can, therefore, range from observation to radiation or cryotherapy to testosterone deprivation therapy with Lupron and even to chemotherapy.

Monitoring PSA After Surgery or Radiation

PSA is vital for the detection of relapsing cancer after surgery or radiation.  Normally, after surgery PSA should drop to an undetectable level.  Even small rises of PSA are an indication of possible cancer recurrence.  After radiation, assuming the disease has been cured, the PSA generally remains under 1.0 indefinitely.

  However, with radiation there are exceptions. First, PSA levels often decline slowly after radiation, sometimes taking several years to reach their lowest point.  Second, temporary rises in PSA can occur, especially after the seed-implant type of radiation.  Noncancerous PSA increases, termed “PSA Bumps” can develop after 1 to 4 years, creating consternation about the possibility of cancer recurrence.

  The PSA Bump is thought to result from a delayed immune reaction in the prostate.  The good news is that a PSA Bump may actually be associated with higher cure rates.  The bad news is that misconstruing a bump as a recurrence may frighten men (and their physicians) into initiating unnecessary hormone therapy. 

Defining the Different Types of Relapses

When a cancer recurrence is confirmed, the rate of PSA doubling indicates the tumor’s aggressiveness. For example, PSA that requires more than 12 months to double, represents a very low grade recurrence - one that may not even require treatment. On the other hand, cancer that requires less than three months to double is behaving aggressively.  Ultimately, treatment for relapsed disease is guided by three things:  the original risk-category prior to surgery or radiation (Low vs. Intermediate vs. High), the PSA doubling time and the location of the relapsing cancer determined as best it can by scanning, or by what an experienced prostate cancer doctor surmises.

The PSA Doubling Time

Treatment selection is heavily influenced by the rate of PSA rise.  For example, if the PSA doubles in less than three months (or even less than six months), aggressive combination treatment with Lupron plus radiation (or cryosurgery in men previously treated with radiation) is probably required.  If the PSA doubling rate is between six and 12 months, a less aggressive treatment approach with radiation alone, cryosurgery alone or intermittent Lupron would be reasonable.  Some men with a PSA-relapsed disease have a condition that grows so slowly and no treatment whatsoever is required. This is the case when it takes more than a year for the PSA to double.

PSA Doubling Times Between Six to 12 months

What about the “in between” situations where the recurrent disease seems to be localized to the prostate or prostate fossa, the nodes are clear, the original risk-category was Intermediate-Risk and the PSA doubling time is between six to 12 months?  Should  a man with prostate cancer have local treatment alone with radiation or cryotherapy?  What about intermittent Lupron alone?  Should we do radiation with a short course of Lupron?  The best answer is that we don’t really know. In a situation like this, patients should familiarize themselves with all the potential side effects of each of these different courses of action. Personal preference is a perfectly reasonable selection technique.  

Very Fast PSA Doubling Times 

A brisk PSA doubling time, say three months or less, is a powerful indication of a potentially life threatening situation. Even though the scans may be clear, treatment should be aggressive. Even using unorthodox treatment may be warranted. New agents such as Zytiga or Xtandi might be considered. Recent studies also indicate that men have better survival when they take six cycles of Taxotere along with Lupron.  

The Original Risk-Category

In general, treatment should be more aggressive (consisting of a combination of Lupron and pelvic lymph node radiation) if the original risk-category was High-Risk. Treatment should lean toward a less aggressive approach—cryotherapy alone, radiation alone or Lupron alone—if the original risk category was Low-Risk.  

Searching for the Location of the Cancer

Men with rising PSA after surgery or radiation should initially undergo standard imaging studies in an attempt to determine the location of the cancer. Unfortunately, “standard” scans like CT and MRI often fail to detect recurrent cancer, especially if the PSA under 10. Improved PET scans with C11 acetate or choline can detect the location of the recurrent disease with much lower PSA levels. Unfortunately, these PET scans are so new that insurance coverage may be unavailable.

The “standard” scans commonly used are:

  • Color Doppler ultrasound or multi-parametric MRI can be used to look for residual cancer in the surgical fossa after surgery or in the prostate gland in men previously treated with radiation.
  • Pelvic MRI or CT scans are used to check for spread to pelvic lymph nodes. 
  • Technetium bone scans are the old standard. New F18 PET bone scans, however, are preferable because they can detect much smaller cancers than technetium bone scans.

When the Scans Show No Metastases After Surgery

Generally, men who were Low-Risk or Intermediate-Risk prior to surgery and who develop a PSA rise with a doubling time between six to 12 months will have reasonably good cure rates with salvage radiation to the prostate fossa. Alternatively, men who are nervous about the side effects of radiation can consider suppressing the PSA with intermittent Lupron administered for six months. Men who have more rapid doubling times, under six months, for example, should probably have radiation to the pelvic nodes combined with a somewhat longer duration of Lupron, say 12 to 18 months. Men who were High-Risk should definitely consider node radiation with 12 to 18 months of Lupron.  They might even consider adding more powerful agents such as Zytiga, Xtandi or Taxotere.

When the Scans Are Clear After Radiation

For a rising PSA after radiation, one of the most popular approaches is freezing the residual cancer in the prostate with cryosurgery.  This approach has become even more popular with the advent of better scans that enable the cryosurgeon to sub-select a portion of the gland and treat the cancer with focal treatment rather than treating the whole prostate.  Side effects with focal cryotherapy are much milder compared to freezing the whole gland and dramatically less toxic than trying to remove the prostate surgically. Surgical removal of the prostate after radiation should almost never be considered due to the extremely high rates of incontinence and impotence. 

Another alternative in this situation is to give Lupron intermittently. This will effectively suppress the local disease and this is a reasonable consideration in men with doubling times over six months if the original risk category was either Low-Risk or Intermediate-Risk. Men who have local relapses but who were originally High-Risk are probably better served by an aggressive attempt to cure the disease with cryosurgery or seed implantation rather than simply suppressing the disease with Lupron by itself.

Lupron Alone After Surgery or Radiation When Scans Are Clear

As suggested above, if scans have been completed and the location of the relapse appears to be local, men also have the option of treating relapsed disease with Lupron. Lupron by itself, however, has various side effects and is almost never curative. Even so, disease control for more than ten years is common. To reduce side effects, Lupron can be used intermittently. A typical intermittent protocol consists of treatment administered for six to 12 months after which the Lupron is stopped.  Over time, testosterone recovers and PSA begins to rise.  A second cycle of Lupron is started when the PSA rises back to the original PSA baseline, or up into the three to six range, whichever is lower.  Intermittent Lupron has been a standard approach for managing men with PSA relapse for over 20 years.  Lupron alone is the most logical approach if an attempt at cure is not feasible using radiation or cryotherapy. 

Putting It All Together

So to summarize, in more favorable situations when scans indicate that cancer has not spread to the nodes, treatment with cryosurgery alone or radiation alone is reasonable as long as the previous risk category and the PSA doubling time are favorable.  Of course, even when scans show no metastases, the possibility of microscopic metastases in the pelvic nodes has to be considered.  Microscopic disease is much more likely in men who have fast PSA doubling times or who were High-Risk at the time they were first diagnosed with prostate cancer. In these situations, the addition of prophylactic pelvic lymph node radiation in addition to an extended course of Lupron is advisable.

The treatment selection process for men with a PSA relapse is complex.  The process begins by constructing a patient profile using the original risk category, the PSA doubling time, and the scan findings.  Unfortunately, the location of recurrent cancer may remain uncertain, even after doing the best scans.  When this is the case, the extent of disease may require a professional “guesstimate” based on the PSA doubling time and the original risk-category. Despite all these difficulties and uncertainties, the good news is that a wide variety of treatment options are available. For the majority of men, the disease can be controlled on a long-term basis, and some cases even cured.  The overall outlook is optimistic.  Even for those who aren’t cured, the vast majority will be able to keep their disease in check for years if not decades with treatment.

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