Clinical Practice Guidelines for the management of locally advanced ...

4 BIOCHEMICAL RELAPSE
A significant clinical problem both in terms of frequency and lack of data to provide guidance is the
clinical scenario of patients with rising PSA levels and normal testosterone levels following definitive
radiotherapy or radical prostatectomy.
If the PSA rises following definitive local therapy (radical prostatectomy or radiation therapy), this
is either due to residual prostatic cancer in the prostatic bed and/or pelvic or distant metastases.
Very rarely it may be due to residual benign prostatic tissue.
It also should be realised that after radiation therapy there may be an initial PSA rise (‘PSA
bounce’) 1, 2 before PSA declines to a nadir, which can occur as late as two years following
treatment. This is commonly seen after seed brachytherapy.
The options for suspected prostate cancer recurrence following localised treatment to the gland with
curative intent are further local treatment or systemic therapy in the form of androgen deprivation
therapy (ADT). If ADT is going to be given, there is a question as to whether it should be started at
the first evidence of PSA rise or when disease is evident with imaging.
However, one must appreciate there are different patient groups in this setting.
For example, patients with high-risk disease (and most with intermediate-risk disease) that have
had definitive radiotherapy with curative intent will have had this in combination with hormonal
therapy. In this situation, one needs to distinguish whether their progression is with a normal or
castrate testosterone level.
Another group will be hormone naïve and some of these patients (~20% of men over 60 years)
may actually be hypogonadal due to testicular atrophy. 3
Some patients after prostatectomy may have received adjuvant radiation therapy and therefore
differ to those who have not had prior radiation to the prostatic fossa.
A rising PSA after radiation therapy is also a difficult problem to manage. Local therapy such as
resection of the prostate after radiation or other procedures such as cryotherapy can also be
considered. However, these are not routine and they have significant risks, such as furthering the
chance of incontinence and impotence and, with procedures such as cryotherapy, of fistula
(connections) between the bladder and rectum.
It is recognised this a very complicated clinical situation with outcomes predicated by patients’ life
expectancy, prior therapy and the innate biological characteristics of the cancer (rapid versus
indolent). This situation also causes a lot of angst for patients. There are some patients with a very
indolent course and the toxicity of early and prolonged ADT may be detrimental.
4.1 Salvage radiotherapy
Patients who have not had prior radiation therapy are candidates for ‘salvage radiation’. These
patients are often detected by a PSA rise post-prostatectomy. Salvage radiation is not an option for
patients with prior definitive or adjuvant radiation. Unlike adjuvant radiation, there are no randomised
phase III trials. The results of ‘salvage radiation’ are based on retrospective reviews and reported in
terms of metastasis-free and overall survival. Patients with a lower PSA level at time of salvage
radiation have a better chance of a longer PSA-free survival. 4 There are no randomised controlled data
to define the benefits of salvage radiation versus adjuvant therapy or salvage radiation versus systemic
therapy (either at time of PSA rise or at time of radiographic progression). The Trans-Tasman
Radiation Oncology Group (TROG) is conducting a study of adjuvant radiation versus salvage
therapy to help address this unanswered question.
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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