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  Volume 96
Numero 3
maggio-giugno 2010 		I documenti sono in formato PDF, consultabili utilizzando Acrobat Reader
 
In reply

We read with interest the letter of Franco et al. We fully agree that the choice of salvage therapy in prostate cancer is a highly patient-tailored decision. Indeed, more and more salvage modalities are being investigated for isolated primary recurrent prostate cancer, including prostatectomy, high-intensity focused ultrasound, cryotherapy, radiofrequency interstitial tumor ablation and re-irradiation1.
Isolated locally recurrent prostate cancer constitutes a particular clinical situation. Most recurrent prostate cancer patients have been treated with high-dose radiotherapy (>70 Gy), and clinically evident or subclinical normal tissue damage may be present. Due to the long natural history of the disease, the diagnosis of recurrent tumor is usually done more than 5 years after the primary radiotherapy course, so aging and comorbidity make the clinical decision on the salvage approach even more challenging than the primary treatment choice. In fact, the recent reports on the high risk of rectal fistulae following salvage high-intensity focused ultrasound after combined brachytherapy and external beam radiotherapy emphasize the fragility of this patient population 2. Definitely, the emerging ablative therapies regarded as less invasive than traditional therapies must be used with caution.
Re-irradiation is probably the most investigated local approach for recurrent prostate cancer. Re-irradiation may be performed in numerous ways including low dose rate and high dose rate (HDR) brachytherapy, linac-based stereotactic irradiation or robotic image-guided stereotatic irradiation using a CyberKnife unit.
We fully agree with Franco et al. that the choice of the re-irradiation modality should be based on the clinical and radiobiological context. In the case of our patient, the choice of HDR brachytherapy was based on the absence of radiotherapy late toxicity and the emerging data on the low α/β of the prostate cancer3-4. According to the linear quadratic model, the equivalent biological dose EQD given at 2 Gy per fraction (EQD2 = D[α/β+d]/ [α/β+2], where D is the total dose given at the dose per fraction d) of our HDR schedule, is 64.3 Gy, 61.2 Gy or 53.5 Gy, assuming the α/β value of 1.5 Gy, 1.85 Gy or 3.1 Gy, respectively. Obviously, the entire knowledge on the α/β of prostate cancer comes from the primary tumor, whereas the radiobiology of recurrent prostate cancer (different α/β ratio?) still has to be investigated.
Low dose rate brachytherapy might be a better choice in a patient who has experienced late injury or severe acute toxicity during the first radiotherapy course that might evolve in the clinically evident late events due to consequential effects.
Reports on the low α/β of prostate cancer have stimulated the introduction of hypofractionated radiotherapy for the malignancy5. Actually, HDR brachytherapy is a form of extreme hypofractionation when the whole therapy is given in a very short overall time. HDR schedules have been transferred to high precision external beam radiotherapy using the CyberKnife. Indeed, the recent planning study from San Diego, CA (USA), showed that it is possible to construct CyberKnife plans that closely recapitulate HDR dosimetry and deliver the plans noninvasively6. In 2007, we started using CyberKnife re-irradiation for prostate cancer patients with isolated local recurrence after external beam radiotherapy. Our preliminary report on 6 cases showed excellent local tumor control and toxicity profile7. However, half of the patients experienced distant disease progression, even though androgen deprivation was employed in 4 of the 6 patients. Such patterns of failure call for better definition of selection criteria and optimization of systemic treatment in patients undergoing salvage re-irradiation for prostate cancer.

Barbara Alicja Jereczek-Fossa, Andrea Vavassori, Roberto Orecchia
1Dept of Radiotherapy, European Institute of Oncology, Milan; 2University of Milan, Milan, Italy

References
1. Nguyen PL, D’Amico AV, Lee AK, Suh WW: Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature. Cancer, 110: 1417-1428, 2007.
2. Ahmed HU, Ishaq A, Zacharakis E, Shaw G, Illing R, Allen C, Kirkham A, Emberton M: Rectal fistulae after salvage high-intensity focused ultrasound for recurrent prostate cancer after combined brachytherapy and external beam radiotherapy. BJU Int. 2009 103: 321-323, 2009.
3. Fowler J, Chappell R, Ritter M: Is alpha/beta for prostate tumors really low? Int J Radiat Oncol Biol Phys, 50: 1021-1031, 2001.
4. Dasu A: Is the α/β value for prostate tumours low enough to be safely used in clinical trials? Clin Oncol (R Coll Radiol), 19: 289-301, 2007.
5. Fowler JF, Nahum AE, Orton CG: Point/Counterpoint. The best radiotherapy for the treatment of prostate cancer involves hypofractionation. Med Phys, 33: 3081-3084, 2006.
6. Fuller DB, Naitoh J, Lee C, Hardy S, Jin H: Virtual HDR CyberKnife treatment for localized prostatic carcinoma: dosimetry comparison with HDR brachytherapy and preliminary clinical observations. Int J Radiat Oncol Biol Phys, 70(5): 1588-1597, 2008.
7. Vavassori A. Jereczek-Fossa BA, Beltramo G, De Cicco L, Fariselli L, Bianchi LC, Possanzini M, Bergantin A, DeCobelli O, Orecchia R: Image-guided robotic radiosurgery as salvage therapy for locally recurrent prostate cancer after external beam irradiation: retrospective feasibility study on six cases. Tumori, 96: 71-75, 2010.



 
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