When Disease Recurs...Diagnosis and Treatment Options

Dr. Guy Bernstein, Urologist, Byrn Mawr Hospital

Failed radiation therapy (RT)

If disease is local, cryo could be considered. It looks good for lower grade disease. Incontinence could be a problem in up to 30%, although some cryo surgeons are having better results than that. RP could be considered in younger men, but the complications of rectal injury, incontinence, and urinary strictures are very common.

Failed radical prostatectomy (RP)

Decisions need to be based on two issues. Was the PSA ever undetectable following RP? Is the disease thought to be local or systemic? A work-up would normally include a bone scan; trans-rectal ultrasound (TRUS), with or without a biopsy; and ProstaScint. Although the latter is quite new, it appears to be much better in this setting than MRI or CT. If the ProstaScint is positive in the pelvis only, salvage RT will be more likely to be successful than if the ProstaScint is negative, or positive outside the pelvis. The best candidates for salvage RT had undetectable PSA post RP, a time to PSA or clinical failure of greater than 40 months, and tests indicating local disease. There is a 50% response rate in this setting (PSA going "toward" undetectable).

Hormone therapy (HT)

When used for recurrence, HT will always fail. However, if the initial response to HT was good, a second line of intervention using Ketoconazole or other agents will probably be good. One type of HT being tried for recurrence is high-dose Casodex at 150mg per day, with or without Proscar, but it is too early to comment on the results.

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Date: Tue, 30 Sep 1997 14:00:18 - 0400
From: Bob Southard <southard@EPIX.NET>
Subject: Notes, Philadelphia conference, Part 2 of 2

Prostate Cancer Issues and Answers
A conference for patients, sponsored by the ACS and Man to Man.
September 27, 1997, Philadelphia, PA

The following are some of my notes from the meeting. I've tried to accurately reflect what was said, but can't guarantee the reliability of these notes. The quotes are paraphrases, and ultimately, they are my interpretation of what I heard. I share these notes in the hope that someone may find something of value.

Management of Possible Side Effect of Treatment:
Incontinence, Impotence, Hormonal Side Effects (Part 1)

Barbara Zoltick, RN, MSN (Urology, Oncology),
U of Penn Cancer Center

Hot flashes due to HT in men can be coupled with a strong feeling of anxiety and impending doom, especially when awaking at night. A 20mg dose of Megace two times a day, will help hot flashes in 80% of men, but beware of side effects. Hot flashes are associated with a release of catecholamines in the body, resulting in a racing heart and the psychological impact.

Breast swelling on HT can often be prevented by low dose radiation to the breast BEFORE HT is undertaken. Casodex in high dose can cause breast swelling in 50% of men.

Liver enzymes should be measured every month while on combined HT (CHT).

Anemia often occurs 5-6 months after the start of CHT. Treatment is available.

Osteoporosis most often offers in men who are small, thin, and smoke.

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Management of Possible Side Effect of Treatment:
Incontinence, Impotence, Hormonal Side Effects (Part 2)

Dr. Gregory Broderick, Urologist,
Hospital of the Univ. of Pennsylvania

The side effects of RP are

• Mortality --0.2%
  
• Rectal injury --1%
  
• Bladder Neck Scarring --8-10%
  
• Incontinence --8% that need further surgery
  
• nearly 100% that find troublesome side effects
  
• Impotence --data is all over the map. It depends who you ask, doctors or patients.
  

For incontinence, do Kegels first and foremost. Do these before and after surgery. Do these for the rest of your life. These benefit the accessory muscles to the urethral sphincter.
The side effects of RT are

• Acute proctitis -- common, inflammation. of the rectum that passes
  
• Acute cystitis -- common, inflammation of bladder that passes
  
• Urethral stricture --up to 15%
• Incontinence --less than 5%. This is different than RP incontinence, which gets worse with physical pressure or stress. RT incontinence is urge incontinence due to hardening of the bladder. When you've got to go, you get little warning. You need to get up more frequently at night.
• Impotence --5-40%, occurring up to 6 months after therapy
  

The side effects of brachytherapy (seeds) are

• Acute proctitis --less than 2%
  
• Acute cystitis --less than 2%
  
• Rectal ulceration --less than 12%
  
• Leakage incontinence --only seen if a transurethral resection (TURP) was done.
  
• Urinary retention --3-12%, the lower number seen when men are on HT.
  
• Impotence --40%
  

The side effects of cryosurgery are

• Urinary retention --30%
  
• Incontinence --30%
  
• Passing (sloughing) tissue --20%
  
• Perineal pain --11%
  
• Urinary stricture --3%
  
• Sepsis (blood poisoning/infection) -3%
  
• Fistula (to rectum) --1-3%
  
• Urethral (ureter) blockage --2%
  
• Impotence --100% at 24 months post surgery.
  

Muse (the suppository used for erection) must be used carefully. Some of the chemical is released in the ejaculate (if there is any), and can result in burning and swelling to sensitive tissues (including the mouth).

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New Radiation Therapies, Conformal Radiation Therapy (3DCRT)

Dr. Gerald Hanks, Chair, Dept of Rad. Oncology,
Fox Chase Cancer Center

200-250 centers out of 1500 in the US now do 3DCRT.

At Fox Chase, every patient is placed in a body-fitting cast, which helps locate the target by an extra 1 cm. This reduces necessary margin by 50%.

A CT scan is complimented by a urethragram to clearly image the apex. 3DCRT provides a 14% reduction in exposure to the bladder neck and rectum, compared to conventional RT.

As of March, 1997, they have treated 1008 patients with 3DCRT, of which 229 also had combined HT.

Given two ways to measure response, PSA less than 4.0, and PSA less than 1.5, the following data was presented for PSA response at 12 months post treatment, 3DCRT vs conventional therapy:

Stamey's statement that 80% of men have a rising PSA 5 years after RT is a "lie." At Fox Chase, over 60% of men treated are disease- free.

The response rate rises rapidly when dose is increased from 65 Gy to 80 Gy, and treatment curves were shows to support this. Only 3DCRT can deliver the high doses needed to best response.

Late RTOG Grade 3 and 4 complications (the worst kind), are seen in 4.5 to 10% of cases in conventional treatment with doses of 65-70 Gy, and less than 1% of cases in 3DCRT with doses of 70-80 Gy.

In using 3DCRT for salvage therapy following RP, a target is defined by estimating where the prostate and seminal vesicles were located (via CT). The 3DCRT technique will reduce the exposure of normal tissues by 15-20% compared to conventionWhen Disease Recurs RT in this setting.

When Disease Recurs

Adding CHT to 3DCRT looks most promising in high grade tumors, In cases with Gleason 8, 9, and 10. There is a survival advantage at 5 years. In cases with PSA over 20, staged T3 or T4, adding CHT showed a survival advantage of 15-17% at 5 years.

In metastatic disease, patients going on CHT do better if the pretreatment testosterone level is high, rather than low.