Brachytherapy in the Treatment of Localised Prostate Cancer
no prognostic significance relative to recurrence, but can confound the diagnosis of recurrence.49
a minimum of three years post-LDR BT with 125I.51
In a recent study, patients were followed for PSA bounces of ≥0.2,
≥0.4, ≥0.6 and ≥0.8 ng/ml were noted in 247 (30.1 %), 161 (19.6 %), 105 (12.8 %) and 78 (9.5 %) of the patients, respectively. Although there are several views as to bounce definition, a rise of ≥0.2 ng/ml is considered to be a reliable measure of an increase.51
However, the time to first
PSA rise is actually the most valuable factor for distinguishing between a bounce and biochemical failure. This is because a PSA rise that corresponds to a bounce usually occurs much earlier than a PSA rise that corresponds to a failure (approximately 18 months versus 34 months). It is not possible, however, to guarantee that an early rise is a bounce until PSA begins to decrease and thus levels must be closely monitored.
Cancer Control
Disease-specific survival has been shown to be 98 % in patients with a Gleason score of ≤6 (see Table 2).52
The authors
reported the 10-year LDR BT results from the treatment of 152 consecutive patients with clinically organ-confined prostate carcinoma. Ninety-seven patients (64 %) remained clinically and biochemically free of disease at 10-year follow-up.19
Furthermore,
a combination of LDR BT and EBRT resulted in good outcomes in patients with clinically localised cancer and at high risk of extra-prostatic spread. This was confirmed in a retrospective study of high- and intermediate-risk patients (n=689), in whom a combination of BT and EBRT resulted in a biochemical recurrence-free survival (bFS) rate of 88 % at seven-year follow-up.53,54
Several other studies, involving a total of more than 3,000 patients, have observed clinical disease-free survival rates of between 78 and 98 % in low-risk patients following 125I LDR BT during follow-up protocols of 8–12 years.46,56–59
Overall, these long-term
follow-up studies demonstrate that LDR BT is an effective treatment for clinically localised PCa.
In several studies, D90 levels have been correlated with clinical outcomes and PSA control. Optimal implant dose distribution is critical to ensure delivery of the prescribed dose to the prostate and achieve long-term biochemical/clinical control. Stock et al. first demonstrated that a D90 of at least 140 Gy, as calculated on the basis of the post-implant CT, correlated highly with freedom from biochemical failure.60
Patients receiving a D90 <140 Gy had a four-year bNED rate
of 68 % compared with a rate of 92 % for patients with a D90 >140 Gy. A subsequent eight-year follow-up of these data demonstrated the durability of the >140 Gy dose response, with an eight-year bNED
EUROPEAN UROLOGICAL REVIEW
A recent multicentre prospective study compared the impact of RP, LDR BT and 3D EBRT on the HRQoL of patients (n=614) with localised PCa.70
79 RP was shown to have a considerable negative impact on
There have been several recent studies that have reported results from lengthy follow-up of LDR BT in patients with localised PCa. In one study, involving a 12-year follow-up of 1,656 patients with PCa, it was observed that biochemical progression-free survival (bPFS), cause-specific survival (CSS) and overall survival (OS) for the group as a whole were 95.6, 98.2 and 72.6 %, respectively.55 bPFS at 12 years was 98.6, 96.5 and 90.5 % for men with low-, intermediate- and high-risk disease, respectively. For men with Gleason score 5/6, actuarial biochemical failure at 12 years was 1.8 % and cancer-specific mortality was 0.2 %. For men with Gleason score 7 disease, the rates were 5.1 and 2.1 %, respectively. Over 90 % of biochemical failures occurred within 3.9 years of implantation.55
LDR BT in low-risk patients results in a high rate of biochemical control and has increased in use since the publication of a 10-year analysis.19,52
(American Society for Radiation Oncology [ASTRO]) of 91 %, versus 62 % for the <140 Gy dose (p<0.001) using the same dosing criteria.61
Achieving optimal dose delivery requires highly trained and experienced urologists, radiation therapists and physicists. A review of 2,693 patients revealed a bFS rate of 93 % eight years after receiving quality implants whilst lesser-quality implants showed a reduced rate of 76 %.46,62
These
data highlight the importance of correct implantation of BT seeds, a procedure that should only be performed by experienced physicians. Precise implantation leads to reduced PSA values and substantially improved clinical outcomes.
Comparing the Efficacy of Low-dose-rate Brachytherapy with Radical Prostatectomy and External-beam Radiotherapy
Several groups have established that RP and BT are equally effective options for patients with low-risk PCa.63–65
In a landmark study, D'Amico
et al. evaluated a total of 1,872 men treated with an RP or LDR BT with or without neoadjuvant androgen deprivation therapy, or EBRT.63 The outcomes of five-year PSA estimates were not significantly different following treatment with RP, EBRT or LDR BT with or without neoadjuvant androgen deprivation in low-risk patients. However, intermediate- and high-risk patients treated with RP or EBRT did better than those treated by implant.63
A study of the relative efficacy of
This is supported by another retrospective study in which the seven-year recurrence-free survival rate was not significantly different for LDR BT and RP.65
LDR BT and RP observed that after RP the seven-year bPFS rate using the PSA threshold, which is generally employed after radiation therapy, was 89 %, which was not significantly different from the BT group.64
Quality of Life and Adverse Events Several therapy options are now available for the treatment of PCa and have similar efficacy and outcomes. As a consequence, health-related quality of life (HRQoL) and adverse events are now primary considerations for the choice of treatment. Recommendations have been published to assist in the reporting of morbidity after BT and thus to facilitate the comparison between different series.66
Health-related Quality of Life
A prospective study assessed HRQoL during the first year following three treatment methods for clinically localised PCa (interstitial BT, EBRT and RP). The results showed significant decreases in HRQoL in the first month after BT or RP, but not after EBRT. The IPSS increased in the first month after LDR BT, but all quality-of-life (QoL) measures returned to baseline by three to six months;67
one year after treatment,
the QoL scores were not statistically different from the baseline measures for any group.68
A study in the US used a questionnaire that is
supported by the European Organisation for Research and Treatment of Cancer to investigate the complications experienced by 160 consecutive patients who had received BT for PCa. The study showed that following the procedure, 38 % of patients required non-routine visits to a physician office or treatment centre and 5 % were found to have radiation proctitis, although none of these cases required surgery. The majority of adverse events reported in the study were self-limiting and there was no treatment-related mortality following BT.69
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