Chapter 091. Benign and Malignant
Diseases of the Prostate
(Part 8)

For patients with a rising PSA after radiation therapy, salvage
prostatectomy can be considered if the disease was "curable" at the outset, if
persistent disease has been documented by a biopsy of the prostate, and if no
metastatic disease is seen on imaging studies. Unfortunately, case selection is
poorly defined in most series, and morbidities are significant. As currently
performed, virtually all patients are impotent after salvage radical prostatectomy,
and ~45% have either total urinary incontinence or stress incontinence. Major
bleeding, bladder neck contractures, and rectal injury are not uncommon.
In many cases, the rise in PSA after surgery or radiation therapy indicates
subclinical metastatic disease. In these cases, the need for treatment depends, in
part, on the estimated probability that the patient will show evidence of metastatic
disease on a scan and in what time frame. That immediate therapy is not always
required was shown in a series where patients received no systemic therapy until
metastatic disease was documented. Overall, the median time to metastatic
progression was 8 years, and 63% of the patients with rising PSA values remained
free of metastases at 5 years. Factors associated with progression included the
Gleason grade of the primary tumor, time to recurrence, and PSA doubling times.
For those with Gleason grade ≥8 tumors, the probability of metastatic progression
was 37, 51, and 71% at 3, 5, and 7 years, respectively. If the time to recurrence
was <2 years and PSA doubling time was long (>10 months), the proportion with
metastatic disease at the same time intervals was 23, 32, and 53%, vs. 47, 69, and
79% if the doubling time was short (<10 months). A difficulty with predicting the
course of disease in the rising PSA state is that most patients receive some form of
therapy before the development of metastases. Nevertheless, predictive models
continue to be refined. PSA doubling times are prognostic for survival. In one
series, all patients who succumbed to disease had PSA doubling times of 3 months
or less. Most physicians advise treatment when PSA doubling times are 12 months

result in a clinical flare of the disease. These agents are therefore contraindicated
in men with significant obstructive symptoms, cancer-related pain, or spinal cord
compromise.
Agents that lower testosterone are associated with an androgen-depletion
syndrome that includes hot flushes, weakness, fatigue, impotence, loss of muscle
mass, changes in personality, anemia, depression, and a reduction in bone density.
The bone changes can be prevented by treatment with bisphosphonates along with
vitamin D and calcium supplementation. GnRH analogues also lead to an
alteration in body composition and to glucose intolerance. Many taking them
develop the metabolic syndrome.