The INDIGO Shade of Blue

BY MARK SCHOLZ, MD

Prostate cancer is a vast and complicated field. To make it more manageable, PCRI breaks it down into five separate Shades of Blue. Men with recurrent disease after surgery or radiation are in the INDIGO shade. The outlook for men with INDIGO is optimistic.  Some men can still be cured. For those who can’t, the vast majority will be able to keep their disease in check with treatment.

A rising PSA confirmed on sequential measurements is the most common sign of a relapse.

Less common signs of relapse are:

a.     A positive biopsy from the prostate fossa. The “fossa” is where the prostate gland used to be prior to surgery (also, a nodule may or may not be felt on digital rectal examination)

b.    Persistent prostate cancer detected in the gland after radiation by needle biopsy, or by scans or by digital rectal examination

c.     Prostate cancer that has been detected in the pelvic lymph nodes by a scan.

 

People need to be aware that a PSA elevation after surgery or radiation can occur for noncancerous reasons, including incomplete removal of the prostate gland after surgery, prostate tissue “left behind” in the fossa, results in low but persistent levels of detectable PSA.

After radiation, the prostate gland remains in place. Therefore, in men who have been recently treated with radiation combined with testosterone inactivating pharmaceuticals (TIP), discontinuing TIP will lead to testosterone recovery which causes PSA levels to rise. Also, radiation-induced inflammatory reactions can occur in residual prostate gland cause a PSA rise. This rather common phenomenon is called the “PSA Bump.”  It’s essential to be aware of the noncancerous causes of PSA elevation so that well-intentioned but unnecessary treatment can be avoided.  

INDIGO men will require imaging studies to determine the extent of the disease.

1.     Color Doppler or MRI is used to look for residual cancer located in the surgical fossa or in the prostate gland in men previously treated with radiation. 

2.     Pelvic MRI or CT scans are used to look for spread to pelvic lymph nodes. (Carbon 11 acetate PET scan is more accurate than CT or MRI but is still considered to be under investigation)

3.     CT or MRI of the abdomen and bone scans are used to detect the presence of more distant spread to lymph nodes outside the pelvis or to the bones. Scan-detected disease outside the pelvis or in the bones changes the shade to ROYAL. 

Treatment for INDIGO

Treatment options include observation, radiation, TIP, cryotherapy, or combinations of TIP with radiation or cryotherapy. Treatment selection is guided by four factors—the cancer location, the original Shade, the PSA doubling time and a patient’s age. By incorporating all four factors into the treatment selection process, the risk over-treating, i.e., incurring unnecessary side effects from treatment, is reduced.  Awareness of all four of the factors also helps to avoid another common mistake—under-treating—which reduces the likelihood of achieving durable remission.

An isolated “local” relapse is one that appears to be localized inside the prostate after radiation. Local relapse may be curable with cryosurgery alone.  An isolated “local” relapse in the prostate fossa after surgery may be curable with radiation alone.

When no local disease can be detected and when all the scans are clear—termed a “pure” PSA relapse—treatment selection will be influenced primarily by the rate of PSA rise. For example, if the PSA is doubling in less than six months, aggressive combination treatment with TIP plus radiation or TIP plus cryosurgery may be best.  If the PSA doubling rates is between six and twelve months, a less aggressive treatment approach with radiation alone, cryosurgery alone or intermittent TIP alone, is reasonable.  When the doubling time is greater than 12 months, observation without immediate treatment may be considered.

A patient’s age and the original shade at the time of diagnosis also need to be factored into the treatment decision-making process. Men who are more elderly can “step down” the intensity of their treatment plan by temporizing with mild forms of TIP, such as low-dose Casodex. Younger men, who prior to relapse, were in the High-Risk (AZURE) category may want to consider prophylactic pelvic lymph node radiation, a more intensive type of TIP with Zytiga or Xtandi or even chemotherapy with Taxotere.    

Side Effects of Treatment—INDIGO

The residual prostate gland after radiation is anatomically close to the rectum, urinary bladder, and the nerves that control erections. Therefore treatment with salvage radiation or cryotherapy increases the risk of additional long-term sexual, urinary or rectal dysfunction beyond what has already caused by the original surgery or radiation.

Men who are already struggling with incontinence problems from previous surgery may experience further decline in their urinary control when they undergo radiation directed at the fossa. Men who have cryosurgery for a relapse after radiation almost always become impotent. Incontinence can also occur. Surgery to remove a previously radiated prostate causes very high rates of impotence and incontinence.

Radiation to the pelvic lymph nodes can cause damage to the surrounding intestines with symptoms of cramping, diarrhea or loss of rectal control. Since the advent of intensity modulated radiation (IMRT), however, bowel damage from pelvic radiation is a much less common event.

TIP is a common component of the treatment plan for men in the INDIGO category. The severity of side effects from TIP increases when it is continued for a longer duration. As a result, intermittent TIP is very popular. The intermittent TIP protocol is to continue treatment for six to twelve month after which TIP is stopped and a treatment “holiday” is ensues—assuming the PSA drops below the 0.1/ng threshold. The next cycle of TIP is resumed when the PSA rises back to the original PSA baseline, or up to five, whichever is lower.

The most troublesome side effects from TIP are weight gain and fatigue. Maintaining a careful diet and doing regular exercise is very helpful in offsetting these problems. Low libido, however, only responds to a treatment holiday. Daily Cialis is necessary to reduce the risk of permanent erectile atrophy.

Other side effects of TIP typically respond well to the following medications:  Low-dose estrogen controls hot flashes. Osteoporosis can be prevented by Prolia, Boniva or Actonel. Mood swings stabilize with antidepressants. Breast growth is prevented with nipple radiation or Femara.  Erectile dysfunction can be counteracted with Viagra.

Finding the right type of treatment for men in INDIGO is achieved when the benefit of treatment is weighed carefully against the potential for treatment-related side effects. Fortunately, a wide variety of effective treatment is available for men with INDIGO and the majority will have their disease controlled on a long term basis.

So much for getting “the Blues” when you have prostate cancer!