Active Surveillance for Men with Intermediate Risk Prostate Cancer

BY MARK SCHOLZ, MD

People are starting to become familiar with the modern way of conceptualizing prostate cancer.  When men are newly diagnosed, they are split into three broad categories: Low-Risk, Intermediate-Risk and High-Risk. This system, which was invented by Dr. Anthony D’Amico, is helpful for the proper selection of optimal treatment; men with more favorable types of prostate cancer can receive milder therapy and still maintain normal survival rates.

As far as treatment selection is concerned, as a general rule of thumb, men with Low-Risk disease are encouraged to simply monitor the disease, withholding therapy altogether unless tumor growth is detected on subsequent testing.  At the other extreme, men with High-Risk disease typically undergo combination treatment with three forms of therapy: seed radiation, IMRT and hormone therapy, which is continued for a year and a half.

Treatment recommendations for men with Intermediate-Risk range widely from surgery, to the many types of radiation—IMRT, seed implants, SBRT and Proton therapy to focal therapy, as well as the alternative of simply giving hormone therapy by itself. This wide variety of treatment options is not merely a result of physician bias.  It turns out that the types of cancer that occur in the Intermediate-Risk category also vary widely.  At the “good” end of the spectrum, men with the favorable type of Intermediate-Risk disease have a condition that behaves more like Low-Risk while cancers men at the unfavorable end of the Intermediate-Risk spectrum have a condition that behaves more like High-Risk.

The indicators that define an unfavorable type of Intermediate-Risk disease are multiple intermediate characteristics rather than having a single Intermediate-Risk factor.  For example, it is considered unfavorable when the PSA is over ten and the Gleason is 4 + 3 (instead of 3 + 4) and there are more than 50% of the biopsy cores containing cancer.  At the other extreme are men with the favorable type of Intermediate-Risk disease. These men are characterized by having all the Low-Risk factors in combination with only a single Intermediate-Risk factor.

Making a proper distinction between the favorable and unfavorable types of intermediate risk disease can be monumentally important as it relates to treatment selection. Studies show that men with favorable Intermediate-Risk disease are potential candidates for active surveillance.  A recently published report at this year’s Genitourinary ASCO meeting bears directly on this issue:

In Abstract #82 from the meeting, authored by Ann Caroline Raldow from Harvard, 6500 newly-diagnosed men treated with radiation and hormone therapy at the Chicago Prostate Cancer Center between 1997 and 2013 were evaluated.  Dr. Raldow calculated their survival rate after treatment based on their risk category: low, favorable-intermediate, unfavorable-intermediate, and high. Eight years after treatment 820 men had died, 72 of them from prostate cancer. Men in the favorable Intermediate-Risk category had the same survival rates as men in the Low-Risk category.  Men in either the High-Risk category or in the unfavorable Intermediate-Risk category demonstrated an increased mortality rate from prostate cancer.

Bottom line, the cancer of men with the favorable type of Intermediate-Risk prostate cancer behaves the same as Low-Risk.  Dr. Raldow’s analysis provides further clinical evidence that men with the favorable type of Intermediate-Risk prostate cancer can forgo immediate radical therapy and embark on active surveillance.

 

 

 

Selecting Prostate Cancer Treatment

BY MARK SCHOLZ, MD

"You mean you have never heard of diffusion-weighted imaging” Exclaimed a recently-diagnosed prostate cancer patient to his doctor.  How could his doctor be unacquainted with this important aspect of modern prostate imaging? It’s shocking when a patient realizes he possesses more medical information than the “expert.” 

No One Can Be an Expert in Everything
Actually, in this modern era, this situation is being encountered more and more frequently. It’s not so surprising when considering the explosive growth rate of new medical information. It’s humanly impossible for anyone to stay abreast of every new medical development.  For example, even though urologists “specialize” in diseases of the urinary system, their area of responsibility demands expertise in a wide variety of unrelated but important areas such as urinary infections, prostate enlargement, prostate infections, sexual dysfunction and kidney stones. They also have to be expert at the surgical treatment of such problems as congenital defects, bladder cancer, testicular cancer and kidney cancer… just to name a few.

Prostate Cancer by Itself is Quite Complex
Prostate cancer alone is intricate enough to keep a specialist occupied full time. For example, simply staging prostate cancer is complicated. Prostate cancer staging uses a multimodality profiling system that estimates the likelihood of microscopic metastases outside the prostate using PSA, Gleason grade, and a percentage of cancer-containing biopsy cores.  Now, new imaging techniques are providing further information about the size and location of the cancer within the prostate gland. And even more recently molecular profiling has become commercially available.  Staging prostate cancer properly has become a continually developing art form.

Seeking Advice—Delivered from a Level Playing Field
Equally important is the need to seek out unbiased treatment advice. Unfortunately, the process of rendering advice about treatment options is usually very slanted. Urologists (who are surgeons) usually recommend surgery.  Radiation therapists usually recommend radiation. This is not to imply that these physicians have less than the best intentions.  Over time they just become convinced that what they do is the best option for their patients who are consulting them.

What You Don’t Know Can Hurt You
The number of treatments available for men with newly-diagnosed disease is rapidly expanding.  For example, what was previously known simply as “radiation” now includes IMRT, Proton therapy, Cyberknife, two types of Brachytherapy as well as various combinations of these different radiation modalities.  Hormone therapy options have now expanded beyond traditional Casodex and Lupron to include Zytiga and Xtandi. The management of the potential side effects of hormone therapy requires special training in diet physical fitness, bone integrity and sexual health to limit the risk of lingering damage after treatment is completed. These days, relapsed or advanced prostate cancer requires physicians who are conversant in genetic typing, modern PET scans, immunotherapy and injectable radiation.

Every Journey Begins with a Single Step
So newly diagnosed prostate cancer patients are faced with daunting situation. Clearly there is no simple answer to this tangle of complicated issues. However, the newly diagnosed cancer patient is far from helpless. He has two overriding responsibilities. First, he must learn as many facts as possible by getting thoroughly educated about the different treatments for his specific type of prostate cancer. Second, he must use discernment in the selection of which physicians to consult.

There is Time to Learn
With prostate cancer there is rarely a need to rush into making a treatment decision because it is usually slow growing.  There is plenty of time for the shock of diagnosis to wear off, giving you enough time to get educated about the scientific facts.  Published studies comparing outcomes are available. The PCRI in particular publishes articles that translate scientific information into a patient-friendly format.  Ultimately, all claims about treatment should be supported by references published in the scientific literature.  Selecting treatment for prostate cancer is a high stakes proposition, potentially risking sexual function, urinary function, even life itself.  I want to encourage patients to take a leadership role in the treatment-selection process.

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.