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

 

Imaging is Superior to Random Biopsy

BY MARK SCHOLZ, MD

Recently, our attention has been directed at the overtreatment of low-grade prostate cancer.  While PSA screening has been fingered as the problem, overuse of random needle biopsies is the real culprit. Over a million men undergo biopsies every year to address concerns about the possibility of underlying cancer.  Few people realize, however, that random biopsy reveals low-grade prostate cancer in one out of five men in the general population—even if PSA is normal.

 

Most of these “cancers” are harmless. Even so, it’s hardly surprising that patients with “cancer” want immediate treatment.  The words “low grade” or “microscopic” can’t offset the instinctual fears generated by this venomous word.   Despite dire warnings about the risks of treatment-induced impotence and incontinence—and reassurance from experts that low-grade prostate cancer can be safely monitored—studies show that 85% of men still throw caution to the wind and get treatment anyway.

 

Imaging is “Blind” to Small Low-Grade Cancers

While latent prostate cancers are more common, aggressive prostate cancer is also a reality. After all, 30,000 men die every year of prostate cancer. Back when doctors believed that all types of prostate cancer were universally dangerous, prostate imaging, which often misses small, low-grade lesions, was deemed inadequate. However, now with a more modern perspective we know that color Doppler ultrasound or multiparametric, three-tesla MRI overlook low grade disease while still detecting high-grade disease accurately.  Imaging spares men the shock of an unnecessary cancer diagnosis and unwarranted treatment.

 

Targeted Rather than Random Biopsies

When an overtly suspicious lesion is detected by imaging, a targeted biopsy (a limited number of cores aimed directly at the lesion) is typically recommended. Lesions that are biopsy-negative or show low-grade cancer can be monitored without treatment.  If high-grade disease is diagnosed, further staging followed by counseling about treatment is needed.

 

The doctor who reads the scan summarizes his overall impression which falls into one of three categories:

1. No evidence for high grade disease, no need for biopsy
2. A suspicious lesion is detected, a targeted biopsy is necessary
3. An ambiguous area is detected. Either a targeted biopsy can be considered or alternatively, ongoing monitoring with another scan in 6-12 months can be considered

When to Biopsy Ambiguous Lesions
Imaging “sees” all sorts of things besides cancer including scar tissue, areas of active prostatitis, and nodular areas from BPH. Lesions of greater concern are located in the peripheral zone, over a centimeter in size, bulge the prostate capsule or are associated with increased blood flow or diffusion. An ambiguous lesion may require biopsy if a subsequent scans show an enlarging lesion. Expert judgment that takes individual patient characteristics into account comes into play during a discussion between the patient and doctor about whether or not a targeted biopsy is indicated.

“Cross Checking” Ambiguous Lesions
Color Doppler ultrasound and multiparametric MRI are complementary. In our experience the imaging findings between these two modalities match 80% of the time. However in a minority of cases one imaging modality illuminates a specific lesion more clearly. Therefore, with ambiguous lesions using one modality, we usually consider additional imaging with the other modality before recommending targeted biopsy.

New Technology Brings Growing Pains
You might think that new technological advances would immediately revolutionize prostate cancer management. Not necessarily. Many doctors simply don’t know what’s now available. Those that are aware are often unacquainted with the full capabilities modern imaging can achieve. And finally, even the well informed doctors may be reluctant to venture outside their comfort zone to embrace imaging as a substitute for doing a random biopsy.

Final Thoughts
Lack of awareness about how random biopsy leads to the over diagnosis of harmless, low grade cancers is resulting in a 100,000 men undergoing unnecessary surgery and radiation every year. Forgoing PSA screening altogether is both foolish and dangerous. State-of-the-art prostate imaging, not random biopsy, should be the first step in evaluating men with elevated PSA levels.

Join us in Long Beach, CA at Barnes & Noble Marina June 26, 2014 @ 7pm- Ask the Author: Mark Scholz, MD will be discussing his book, Invasion of the Prostate Snatchers and Men's Health. More June events and details here: https://groups.google.com/forum/#!topic/prostateoncology/H1AE5oeW2jc 

Another Milestone at Prostate Oncology, Father Joe Gets his First Apartment

BY MARK SCHOLZ, MD

Father Joe Johnson has been with Prostate OncologySpecialists since its inception. Twenty years ago, after he retired from parish work, he started pursuing his lifelong interest in medicine and computers by volunteering to do internet searches to help find new treatments for our cancer patients. Doing an internet search does not sound like a big deal today, but back in the early 1990s there was no Internet Explorer (or Netscape Navigator for that matter). Getting online required substantial computer expertise and information could only be accessed through medical libraries by payment of an annual licensing fee. Father Joe was well equipped for his radical career change out of parish work. He had previously spent a number of years as a chemistry teacher at Loyola University.

A few years later, when searching the internet became a more straight-forward proposition, Father Joe asked if he could help out in some other capacity. Our practice had a large database of early-stage prostate cancer patients who were treated with hormone therapy, but we lacked the statistical skills to analyze the results. I knew of Father Joe’s lifelong interest in mathematics, and wondered if he would consider tackling medical statistics on our behalf.

For those of you who don’t know, qualified statisticians are rarer than diamonds and far more expensive and difficult to come by. To make a very long story brief, Father Joe subsequently mastered medical statistics and has coauthored all the scientific publications at Prostate Oncology.

Throughout all the years of unsung service volunteering in our office—which as you probably know, focuses exclusively on the treatment of prostate cancer—Father Joe has been a constant and immovable rock of steadfast optimism and hope, visiting with patients and keeping them company while the doctors and nurses rush around trying to stay on schedule. Sure, after entering an exam room and introducing himself as a Catholic Priest he has to good-naturedly endure innumerable bad jokes about his being there to give last rites. But almost invariably people quickly warm up to his friendly presence. I strongly suspect that some of our long-term patients are only willing to suffer the terrible Marina del Rey traffic because of the pleasure of visiting with Father Joe.

Perhaps it’s reasonable to expect patients to put up with the terrible traffic since they only have to endure it on a periodic basis. But what about me? Back when I lived in Long Beach I used to suffer the traffic daily. Being a problem solver by nature, I began considering the purchase of a limousine. My plan was to black out all the passenger windows and don a cap every morning so that I could pretend I was chauffeuring a passenger and drive in the diamond lane. However, it was Father Joe who rescued me from my law-breaking soul.

One evening, after a long day at the office while bemoaning my own tiresome commute home, I discovered that Father Joe was on the lookout for a new place to live. Once our mutual need was discovered it led to a quick solution. Father Joe had lived in trailers off and on throughout his life. And my home in Long Beach had a huge, unused backyard easily accessible through an alley behind the property. After a quick search of the classified ads, we made a phone call. That same evening we purchased Father Joe’s new home and had it delivered to my back yard. For the next five years Father Joe’s calm and loving presence helped me fight the good fight on the 405 freeway morning and evening.

The privilege of taking the diamond lane was definitely a huge improvement. But in 2003 I got the opportunity to purchase a home ten minutes from the office. The problem was that the backyard of the new house was a hillside, with no place for a trailer. What about Father Joe? My initial calls around the Marina were very discouraging: all I was encountered were ten-year wait lists. But the problem was solved when we found out that a relative of one of our patients owned the marina across the street from the office. Father Joe has been living happily in a boat ever since. Clearly he has friends in high places.

Father Joe’s odyssey of volunteering at Prostate Oncology began twenty years ago when he was a young man. But now at age 82, what the heck is he doing living on a boat? Thank God he has not slipped on the wet dock or fallen into the water off his rocking boat. Last night I showed him a new apartment located a mere three-minute walk from the office but he ended up asking me to take him back to sleep on his beloved boat. After a lifetime spent in the small spaces of boat and trailers, to Father Joe, the one-bedroom apartment is gargantuan. I’ll take another run at getting him to stay at the apartment tonight. If that doesn’t succeed I may have to sink the boat.