Emerging radiobiological data indicates that prostate cancer has a low a/β
-ratio of 1.2-3.0 Gy [22
], suggesting that biological dose escalation can be achieved by hypofractionated treatment schemes. In that context, HDR BRT optimally exploits the radiobiological advantage of large fraction sizes while ensuring superior dose conformality. It enables 3D anatomy-based optimisation of the dose distribution by accurately controlling the radiation source positioning and modulating source dwell times. This permits excellent target coverage while at the same time minimizing dose to critical structures which can occur with LDR BRT due to source migration and tissue deformities [25
The results from this study confirm HDR monotherapy as an excellent option for the definitive treatment of localised prostate cancer. The reported 94% BC at 60 months is in accordance with mature HDR monotherapy data from other institutions, suggesting high PSA relapse-free survival rates for all risk groups. In fact, consistent and reproducible five-year BC rates have been reported for patients with low-risk (85-97%), intermediate-risk (93-97%), and high-risk (79–88%) localised disease [1
]. Even though direct comparisons are difficult, our results are consistent with the experiences of other groups using a similar two-implant approach. Mark et al. [1
] reported an actuarial BC rate of 88% at eight years in 301 patients for all risk groups utilising two implants at three fractions of 7.5 Gy. Rogers et al. [8
] reported a BC rate of 94% at five years in 284 intermediate-risk patients treated with two implants at three fractions of 6.5 Gy. Both institutions included clinical stages ≥ T2b with no exclusions for Gleason score or pre-treatment PSA in the series by Mark et al. [1
]. These recently published data reflect that HDR monotherapy is applicable in intermediate as well as selected localised high-risk cases.
In our cohort, Gleason score, pre-treatment PSA, and clinical stage did not attain statistical significance using Kaplan-Meier actuarial estimates of freedom from biochemical failure. Rogers et al.
], Hoskin et al.
] and Yoshioka et al.
] likewise failed to verify Gleason score and pre-treatment PSA or clinical stage as significant predictors of risk of biochemical failure. Hoskin et al. [3
] reported on a group of 197 patients with a four-year BC rate of 87% in 86 high risk-cases. Those included clinical stages ≥ T3 in 21%, Gleason score ≥ 8 in 10%, and PSA > 20 in 25% of cases with 92% of high-risk patients receiving temporary ADT. In our study, the BC at 60 months for low-risk, intermediate-risk and high-risk patients was 94%, 92% and 92%, respectively. There was no statistically significant difference between these risk groups, indicating that all patients benefited equally. However, 60% of the high-risk patients received temporary ADT including all patients with PSA ≥ 20 ng/ml, 93% of patients with Gleason score ≥ 7b (4+3), and 52% of all cases staged > T2b. At this point, the potential advantage of short term androgen suppression for high-risk patients remains an issue of ongoing discussion as no corroborative evidence exclusive to this modality exists.
Gastrointestinal and genitourinary morbidity was low in our series with toxicity incidences across all scales consistent with those reported by other authors [1
]. We encountered 3.4% late Grade 3 genitourinary toxicity with seven patients developing strictures requiring urethrotomy. Late Grade 3 rectal morbidity was 1.4% overall with one patient requiring endoscopic restoration of bowel continuity after rectal biopsy associated ulcer development. Additionally, in the final questionnaire 83.4% of patients reported erectile function, with or without the use of medical aids, suitable for intercourse. This rate of erectile preservation is consistent with data reported in recent publications on HDR monotherapy [8
]. The consistently low level of severe acute and late toxicities in HDR BRT likely reflects the precision of 3D dosimetry, which can reduce uncertainties in dose distribution and thereby allow for better sparing of critical organs [28
In accordance with the experience of other groups [8
], neither larger gland size nor previous transurethral resection of the prostate (TURP) were absolute contraindications for treatment. The transperineal approach in high dorsal lithotomy position enables adequate implantation of volumes appreciably greater than 50 cc provided there is a sufficiently broad pelvic inlet and low pre-treatment urinary symptom scores. In the same way, implantation at six months after TURP was safely feasible given a sufficient amount of residual gland volume.
There are of course some limitations in our study. It encompassed 351 patients who were not treated within a multi-institutional framework but at a single tertiary-care center. The data was generated from a prospectively maintained database which was analysed by retrospective chart review. Our treatment modality has also limitations. Intraprostatic calcifications may impair TRUS imaging quality thereby limiting real-time US-based treatment planning and dose conformality. Therefore, the “technical eligibility” of each patient should be evaluated through a TRUS examination prior to treatment. Finally, the presence of seminal vesicle invasion or large prostate gland volumes extending beyond the bony pelvic inlet, also disqualify patients for monotherapy [28