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’) 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.
- 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.
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.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.
- Horwitz EM, Levy LB, Thames HD, Kupelian PA, Martinez AA, Michalski JM, et al. Biochemical and clinical significance of the posttreatment prostate-specific antigen bounce for prostate cancer patients treated with external beam radiation therapy alone: a multiinstitutional pooled analysis. Cancer 2006 Oct 1;107(7):1496-502 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16944536.
- Crook J, Gillan C, Yeung I, Austen L, McLean M, Lockwood G. PSA kinetics and PSA bounce following permanent seed prostate brachytherapy. Int J Radiat Oncol Biol Phys 2007 Oct 1;69(2):426-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17869662.
- Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001 Feb;86(2):724-31 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11158037.
- Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 2007 May 20;25(15):2035-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17513807.