BERKELEY, CA (UroToday.com) - In our recent article, we reported the outcome of hypofractionated proton boost of 20 Gy, in daily 5 Gy fractions, combined with external beam radiotherapy (EBRT) of 50 Gy, in daily 2 Gy fractions, for 63 low-risk, 95 intermediate-risk and 107 high-risk prostate cancer (PC) patients. The median follow-up time for these patients was 5 years. Assuming a value of α/β of 3 Gy or 1.5 Gy and a value of relative biological effectiveness (RBE) for protons of 1.1, the equivalent dose in 2 Gy fractions (EQD2) for this schedule would be 87 Gy or 94 Gy, respectively. This schedule, and the patients set up with the transperineal proton boost with fixed beam of 180 MeV, was the result of combinations of the supporting data of hypofractionated schedules and the practical limitations of the physical proton facility. The initial aim was to provide an alternative to dose escalation for patients not suitable for high dose rate brachytherapy for medical of practical reasons. The 5- and 8-year overall survival of the whole group was 89% and 71%, respectively. Only 8 patients, all being at high-risk, died due to PC after a median time of 58 months (range 35-83 months). The 5- and 8- year prostate cancer-specific mortality was 0% for the low- and intermediate-risk groups compared to 7% and 17% for the high-risk group. We would hereby like to highlight some of the important issues we have found when reporting our data.
Clinical staging of the prostate cancer patients and evaluation of biochemical response
Pretreatment clinical classification (cT) of prostate cancer is still based on digital rectal examination, on which decisions are made whether to treat or not treat, as well as how to treat the patients. For the guidance of the delineation of clinical target volume (CTV), all patients underwent a diagnostic 1.5 Tesla MRI. All of our high-risk patients were meticulously examined for peripheral metastases before treatment. Gleason score and clinical stage have turned out to be a stronger predictive factor for biochemical relapse, compared to PSA, in our multivariate analysis. As our schedule was new, and apart from pathological verification of possible local failures, we have applied all available radiological techniques to verify local, loco-regional and peripheral metastases when biochemical relapse has occurred. Therefore, we could establish that the local recurrence rate was very low. The regional relapse rate was far lower than expected from nonograms. Imaging technologies, such as magnetic resonance imaging (MRI) and different molecular imaging technologies, will hopefully improve the staging of prostate cancer patients and will be accepted, after careful validation, as useful tools in the management of prostate cancer patients as well.
Volume of the prostate and the use of the rectal retraction rod
The median volume of the prostate, measured by transrectal ultrasound at diagnosis, was 37 cc (range, 14-120 cc). Our study group included patients with large prostate volumes and with locally very advanced tumours. Neoadjuvant androgen deprivation therapy (N-ADT) was given for 53% of the patients for a total median time of 6 months. The patients usually started radiotherapy after 3 months of hormonal therapy. The volume determined at the delineation of proton treatment was used in our multivariate analysis when analyzing genitourinary (GU) and gastrointestinal (GI) side effects. The use of the retraction rod for straightening the rectum has significantly reduced the median dose to the rectum wall; however, we could not determine a significant reduction of the already very low reported GI-toxicities. Further studies will be performed on this issue.
Baseline GU and GI symptoms, sexual function and impact of co-morbidity
Evaluating baseline (GU) and (GI) symptoms, as well as sexual function, before any treatment, has been found to be important in the evaluation of side effects. Mild pre-treatment GU-symptoms were found to be a strong predictive factor for later GU-toxicity. This cohort included patients with grades 2 and 3 GU symptoms at baseline, as well. Only 33% of our patient cohort reported normal sexual function at baseline.
TUR-P was found to be a significant predictive factor for GU-toxicities greater than grade 2, while diabetes was found as a significant predictive factor for developing grade 2 GI-symptoms.
Different grades of sexual dysfunction were reported in 66% of the whole group;15% were impotent before treatment. We could not draw any conclusions of the effect of radiotherapy on sexual functions as our study was not designed for that.
Cumulative incidence and the actuarial prevalence of all symptoms
We believe that when reporting the side effects of radiotherapy, both the cumulative incidence and the actuarial prevalence should be reported. Thererfore we have evaluated them for both GU and GI-toxicities. As expected, the cumulative incidence increased for both GU and GI-toxicities, but the prevalence declined significantly with follow-up and reached noticeable low numbers for any grade. Shipley, at al.[1] reported a declining prevalence of both GU and GI-toxicities, indicating a possible slow resolution of epithelial damage. Therefore, we underline that at least another 5-years follow-up is necessary for the accurate evaluation of the true late progressive toxicity of this treatment schedule. Perineal proton boost, preferably with spot scanning, may offer substantial dose escalation and allow hypofractionation be applied safely.
Reference:
- Shipley WU, Verhey LJ, Munzenrider JE, Suit HD, Urie MM, McManus PL, Young RH, Shipley JW, Zietman AL, Biggs PJ, et al. Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone. Int J Radiat Oncol Biol Phys. 1995 Apr 30;32(1):3-12.
Written by:
Silvia Johansson, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Associate Professor
Section of Oncology, Department of Radiology, Oncology and Radiation Science
Uppsala University Hospital
751 85 Uppsala, Sweden
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