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!

The TEAL Shade of Blue

BY MARK SCHOLZ, MD

People assume that the differences in the way prostate cancer behaves—one man develops symptoms and another doesn’t—is because they are seeing different stages of the same illness.  What’s overlooked, often with disastrous consequences, is that these differences are also due to the fact that distinct varieties of prostate cancer exist.

Receiving optimal therapy depends on matching an appropriate treatment with both the correct stage and the correct type of prostate cancer.  Since blue is the color for prostate cancer, as pink is the color for breast cancer, the PCRI has subdivided prostate cancer into five major Shades of Blue. These shades incorporate both the stage and the type of disease. The five shades are SKY, TEAL, AZURE, INDIGO and ROYAL.

The first three shades, SKY, TEAL and AZURE, represent men who have had no previous surgery or radiation. TEAL is what medical professionals call “Intermediate-Risk.” Men in the TEAL shade have identical characteristics to SKY—PSA under 10, Gleason under 7 and a small nodule (or no nodule) on digital rectal examination. However, in addition, men in TEAL have one of the following: PSA between 10 and 20, or, Gleason of 7, or digital rectal exam with a “biggish” nodule confined to one side of the gland.

Since men in TEAL have a small but real chance of cancer spread, staging scans of the bone and body are needed.  In addition, a multiparametric MRI or a Color Doppler Ultrasound should be done to check for spread around the gland just outside the capsule. If extra-capsular disease is seen, the shade changes from TEAL to AZURE.

Treatment for TEAL
The list of treatment options for TEAL is long.  While occasionally men are candidates for active surveillance— particularly those who are older—one of the following treatments is usually administered: Robotic surgery, open surgery, intensity modulated radiation, temporary high-dose seed radiation, permanent seed radiation, a combination of seed radiation and IMRT, proton therapy, Cyberknife, focal therapy or testosterone inactivating pharmaceuticals (TIP).  Sometimes a short course of TIP is combined with radiation.

Focal therapy “focuses” treatment on the cancer itself rather than the whole gland.  Typical tools used for focal therapy are cryotherapy, HIFU or laser. In general, skillfully administered focal therapy is thought to be associated with a lower risk for side effects and only slightly higher risk of future cancer relapse. However, focal therapy is very new and there are relatively few studies accurately describing long-term results.

Another option is to use TIP. TIP causes the cancer to shrivel up.  Typically TIP is continued for six to twelve months after which men are placed on active surveillance.

One general principle is that treatment success depends just as much on the skill of the administering doctor as it does on the type of treatment selected.

The second general principle is that cure rates with most of the different treatments are so close that for comparison purposes, they should be considered identical. Of course, the truth of this principle is predicated on the assumption that all treatments are administered by equally skilled experts.

Side Effects of Treatment
The prostate gland is so close to other critical organs it becomes very difficult to target the gland without damaging surrounding structures. The most common side effects, therefore, are persistent difficulties with sexual, urinary or rectal function.  For example, after radiation in an average 65-year-old, about 75% of men will recover back to their normal pretreatment level of urinary function. About 50% will recover back to their normal pretreatment level of sexual function. After surgery, about 50% of men have urinary function that is restored but only 20% describe their sexual function as recovering back to baseline.

Predictions about the incidence of side effects after focal treatment are less than certain because this technology is so new. Overall, assuming that the treating physicians are skillful, one would expect somewhat better potency rates and somewhat lower cure rates compared to standard surgery or radiation.

Comparing TIP with others options is even more difficult.  Cure rates are certainly much lower. However, the good news is that permanent side effects are rare.  The three most troublesome side effects during therapy are low libido, weight gain and fatigue. Weight gain and fatigue are partially counteracted with diligent diet and exercise. Low libido only resolves after TIP is stopped. Other common side effects such as hot flashes, calcium loss from the bones, mood swings, breast growth and erectile dysfunction can be prevented with medication.

Final Thoughts
Men in the TEAL Shade of Blue, compared to men in the other shades, face the biggest challenge—making a therapeutic choice.  First, there are so many options. Second, none of the options are attractive.  The “best” choice is only relatively better than the others; it’s never something you want to do. Making the best choice for yourself requires good comparison shopping skills, and that requires extensive homework. There are no shortcuts. Third, the biggest differences between the options are not related to the cure rates, it’s the concern about permanent side effects that needs the most attention.

Therefore, my recommendation for selecting treatment is to create a list of all the reasonable choices and study them closely, especially in term of the potential long-term side effects.  The “worst” choices should be eliminated one by one. The last option left on the list will probably be the best treatment for you.