Treatment-related morbidities for prostate cancer patients may be acute, sub-acute or chronic and affect most commonly the urinary, lower gastrointestinal and sexual functions. Many factors have been shown to influence the likelihood of incurring complications, and may allow physicians to better select patients suitable for this approach 24, 47, 48. These reports have also exposed the difficulties in evaluating morbidity due, in part, to the lack of standard assessment methods and potential biases.
Urinary Morbidity and Management
In the immediate post-operative period, patients will likely develop symptoms such as dysuria, frequency and hematuria. The inflammation in the prostate and adjacent tissues may result in weak stream or urinary retention 23, 49. Phenazopyridine (available in the U.S. but not the U.K.) is often helpful with dysuria and alpha-blockers, such as tamsulosin, terazosin, and doxazosin, can be prescribed for irritative urinary symptoms such as frequency and weak stream. Hematuria generally improves spontaneously, but may cause urine retention requiring bladder irrigation. Patients who develop urinary retention may require a catheter placement for an indefinite period of time. Local trauma to the prostate and seminal vesicles can result in hematospermia and orgasmalgia during the first few ejaculatory episodes, and may persist for several weeks.
Subacute urinary morbidity develops one to two weeks after the implant and lasts for several weeks (6-12 weeks). Symptoms generally peak approximately 4-6 weeks after implant for both I-125 and Pd-103 24, 50. Although these symptoms generally resolve over time, many patients will benefit from alpha-blocking agents. Locke et. al. reported prospectively on urinary retention in 62 consecutive patients undergoing permanent prostate brachytherapy with or without external beam radiotherapy 51. At one week, the retention rate was 34% and predictors for retention included prostate size > 36 grams and the preimplant AUA symptom score > 10. The median duration of retention was 70 days with a range of 0 to 469 days. Others that have reported lower retention rates, but similar predictors, such as prostate size and preimplant symptoms to effect the overall chance of developing retention 23, 24, 49. Any surgical manipulations of the prostate to correct for retention should be considered only after all medical options have been exhausted. Trans-urethral incision or a trans-urethral resection of the prostatic urethra for relief of obstructive symptoms can be performed after 2-3 half-lives of the isotope, but is associated with up to a 26% incontinence rate 52.
Chronic urinary morbidity can occur after six months and may include urinary frequency, incontinence, urethral strictures and urethral necrosis 19, 53. In addition, improvements in technique by avoiding high internal radiation doses with peripheral seed placement has resulted in fewer severe long-term urinary side effects 54.
The widespread use of the AUA score allows for standardization of certain morbidities and provides an outline of the severity and course of these symptoms. Desai et. al. reported on urinary toxicity in 117 patients and found a mean doubling of the baseline AUA score, peaking at 1 month following implant and returning to baseline by about 24 months 55. In a later study from the same institution, Terk et. al. showed that the pre-treatment IPSS was an independent factor to predict urinary retention in a multivariate analysis 49. Gelblum et. al. reported urinary toxicity using a modified RTOG scoring system from a large cohort of 693 patients undergoing permanent prostate brachytherapy with or without external beam radiotherapy (Figure 1) 24. The IPSS scores one month after implant were about 3 times that of the baseline scores. There was no significant difference in AUA scores between I-125 and Pd-103 at 60 days and 120 days post-implant.
While there is much published on the urethral sparing technique to help decrease acute urinary morbidity, paradoxically, urinary toxicity is greatest in those with large prostates where peripheral seed placement has the greatest impact on lowering the central prostatic doses 56. Another paradox associated with post-implant toxicity is the use of hormonal therapy to reduce the prostate volume for brachytherapy. As noted, Crook et. al. examined the rate and predictors of acute urinary retention in 150 patients undergoing implant and multivariate analysis showed large prostate volume and prior hormone therapy to be independent predictors of urinary retention (Figure 2) 23. The explanation for this observation may be that with the cytoreduction of the prostate, it develops firmness that does not allow the gland to accommodate to the acute implant prostatitis.