INDIGO: Relapsed Prostate Cancer

MARK SCHOLZ, MD

Those dreaded words, “relapsed cancer,” shake you to the core. They mean that surgery or radiation has failed to “get it all.”  However, while with most cancers “relapse” is a fatal pronouncement.  However, prostate cancer has its own distinct reality. Most men who relapse don’t die from the disease.  The outlook is good because relapses are usually detected by a rising PSA when the cancer is still microscopic. Visible, scan-detected metastases may not appear for ten or more years after the PSA relapse occurs.

Multiple Treatment Options for a Rising PSA
The list of potential treatment options for INDIGO is extensive: observation, radiation, hormone therapy with Lupron and Casodex, salvage seed implant, salvage cryotherapy, Zytiga, Xtandi and Taxotere. However, combinations of these treatments are most commonly employed. Some of these combinations are listed below in order of increasing treatment intensity:  

1.     Observation

2.     Mild hormone therapy consisting of continuous or intermittent Casodex

3.     Monotherapy with fossa radiation, seed implant or cryotherapy for persistent local disease

4.     Combination hormone therapy with Lupron and Casodex given intermittently

5.     Same as #4 but with the addition of pelvic radiation and 4 months of hormone therapy

6.     Same as #5 but with hormone therapy extended for 18 months

7.     Same as #6 but with the addition of Taxotere or Zytiga or Xtandi

Defining Different Types of Relapses
Just as PSA, cancer grade, scan findings and stage were instrumental for assigning a SHADE in newly-diagnosed men; SHADES are important for putting a relapsed in perspective. Ultimately, how to treat INDIGO is guided by a combination of four factors— the SHADE before treatment, the PSA doubling time, individual patient factors such as age, sexual functionality and urinary control, and last, but not least, the cancer location.

The Original Shade before Treatment
In general, treatment should be more aggressive (combined therapy with Lupron and pelvic lymph node radiation) if the original SHADE was unfavorable (AZURE for example).  Treatment should lean toward a less aggressive approach—cryotherapy alone, seed implant alone or Casodex alone—if the original SHADE was SKY.

The PSA Doubling Time
Treatment is heavily influenced by the rate of PSA rise. For example, if the PSA is doubling in less than six months, aggressive combination treatment with Lupron and Casodex plus radiation (or cryosurgery in men previously treated with radiation) is probably required.  If the PSA doubling rate is between six and twelve months, a less aggressive treatment approach with radiation alone, cryosurgery alone or intermittent Lupron and Casodex is reasonable.  When more than a year is required for the PSA to double, observation without immediate treatment may be considered.

Patient Factors that Affect Treatment Selection
A patient’s age needs to be factored into the treatment decision-making process. Men who are more elderly can “step down” the intensity of their treatment by temporizing with milder hormone therapy such as Casodex with Avodart. Younger men, who, prior to relapse, were in the High-Risk (AZURE) category may want to consider upgrading the intensity of treatment by using prophylactic pelvic lymph node radiation plus a more intensive hormone therapy such as Zytiga or Xtandi and/or chemotherapy with Taxotere.

Searching for the Location of the Cancer
Men with rising PSA should undergo standard imaging studies (listed below) in an attempt to determine the location of the cancer. Unfortunately, these scans are often unable detect recurrent cancer unless the PSA is over 20. However, improved PET scans that utilize C11 choline or acetate have the potential to detect recurrent disease with much lower PSA levels. Unfortunately, the PET scans are so new that insurance coverage is often limited.

Sometime even the best scans can’t detect where the cancer is. When this occurs after surgery, particularly when the PSA doubling time is slow, residual cancer in prostate fossa is often suspected and radiation to the prostate fosse is often administered. Cure rates are better when radiation is initiated at a lower level of PSA. 

Standard Imaging Studies for INDIGO

• Color Doppler Ultrasound or Multiparametric 3 Tesla MRI can be used to look for residual cancer in the surgical fossa 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. (Carbon 11 acetate PET scan, however, is far more accurate than CT or MRI but some centers still consider them investigational/experimental)
• Technetium bone scans are standard. New F18 PET bone scans, however, are preferable because they can detect much smaller cancers than technetium bone scans.

Apparent Locally Recurrent Disease

Scans done in a man with a rising PSA after radiation that indicate a recurrence localized inside the prostate, may be curable with cryosurgery alone or possibly with a seed implant alone.  Similarly, an isolated local relapse in the prostate fossa after surgery may be curable with radiation alone. Even though scans show no metastases outside the prostate or the fossa, microscopic metastases in the pelvic nodes may be present, especially in men who have fast PSA doubling times or whose SHADE was originally AZURE.  In these higher risk situations, the addition of prophylactic pelvic lymph node radiation with intensity modulated radiation (IMRT) combined with hormone therapy may be advisable.

Regional Spread to Lymph Nodes

When cancerous nodes are detected in the pelvis, the idea of doing node-directed IMRT is even more compelling. Since overt cancer in the lymph nodes is an indication of potentially life threatening disease, an extended course of hormone therapy, possibly with the addition of second generation hormones such as Zytiga or Xtandi, can be contemplated. Taxotere chemotherapy is an additional consideration.

Hormone Therapy Alone

When the location of the relapse is unclear, or if the risks of side effects from radiation appear too high, relapsed disease can be effectively suppressed for many years with hormone therapy alone. The side effects of hormone therapy tend to increase with longer use so intermittent therapy is very popular. A typical intermittent protocol is to begin with an initial course of treatment for six to twelve month followed by treatment holiday. After hormone therapy is stopped, testosterone starts to recover and the PSA begins to rise. Treatment is restarted when the PSA rises back to the original PSA baseline, or up to five, whichever is lower.

Putting It All Together

Treatment selection for INDIGO can be complex. Constructing a cancer “profile” using the original SHADE, the PSA doubling time, and scan finding, is the first step. Unfortunately, the location of the 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 SHADE.  Despite all these difficulties and uncertainties, the good news is that a wide variety of treatment options are available and treatment is usually very effective. For the majority of men the disease can be controlled on a long-term basis, and some cases it can even cured. 

CALENDAR ALERT TO THOSE WHO LIVE AROUND LONG BEACH, CA Learn more about prostate cancer treatments as Mark Scholz, MD, discusses treating PSA relapsed disease at UsTOO Long Beach Prostate Cancer Support Group July 22, 2014 - 6:30 PM to 8:30 PM, at Long Beach Memorial Medical Center. For more information follow this link: http://goo.gl/HMojNV