Original ArticleEfficacy of High-dose Palliative Radiotherapy for Localised, Castration-resistant Prostate Cancer
Introduction
In men with prostate cancer, the development of castration resistance heralds the emergence of clonogens that have circumvented primary means of androgen deprivation [1]. This phase of the disease is considered end stage in patients with established metastatic disease, with a median survival of about 15 months treated with newer chemotherapy or androgen pathway modulators [1], [2]. A proportion of men, typically those treated with primary androgen deprivation therapy (ADT), develop evidence of castration-resistant prostate cancer (CRPC) without evidence of regional or distant metastatic disease. If no definitive local treatment has previously been delivered, these men represent a management conundrum. The only medical body that currently provides recommendations specifically for asymptomatic or minimally symptomatic non-metastatic CRPC is the American Urological Association. They currently suggest observation with continuation of ADT based on level C evidence [3].
External beam radiotherapy (EBRT) is the obvious modality to control local disease in this highly selected group if symptoms arise, but outcomes of this approach are not well documented. A recent systematic review highlighted the inadequacy of the existing literature in both non-metastatic and metastatic CRPC after pelvic radiotherapy and was unable to make any formal recommendations regarding the optimal dose and fractionation [4].
A high-dose palliative radiotherapy (HDPRT) regimen has been used at our institution for localised CRPC, either when local symptoms become evident or when a patient is considered at imminent risk of their development. The latter is based on clinical evidence of local progression, for example, new palpable tumour progression and/or surrounding tissue invasion. The HDPRT regimens aim to give a total dose of ≥40 Gy with the most common schedule being 50 Gy in 20 daily fractions over 4 weeks. The rationale for HDPRT is that a curative intent dose will probably introduce unnecessary cost, toxicity and time commitment in a group with likely micrometastases and, hence, ultimately, incurable disease, whereas low-dose palliative regimens risk inadequate durability of local control in a cohort that may exhibit extended survival.
The primary aim of this study was to report on clinical local failure in patients who have received HDPRT for localised CRPC. The secondary aims were to report on morbidity inclusive of invasive procedures, tolerability of HDPRT, patterns of disease failure, cause-specific and overall survival. Predictive factors for local failure and overall survival were also explored.
Section snippets
Materials and Methods
Approval for this study was granted from our institutional Human Ethics Committee.
Patient and Treatment Characteristics
In total, 162 patients received a HDPRT regimen in the specified time period. Of these, only 51 patients met the study criteria, with most exclusions being due to the absence of CRPC or the identification of metastases (nodal or distant) before HDPRT. Eighty per cent were deemed node and distant metastasis negative based on imaging within 3 months of radiotherapy, with the remainder based on the absence of suspicion on clinical examination.
Demographic data and disease characteristics for the
Discussion
Localised CRPC is not uncommon when a newly diagnosed patient with N0M0 prostate cancer is treated with ADT alone. In the ADT-only arm of a large randomised trial for newly diagnosed, high-risk prostate cancer, one third of recurrences were identified as local as the first site. The median time to failure from the initiation of primary ADT was 6.8 years [8]. Despite landmark trials showing combined therapy to be more efficacious than ADT alone for high-risk N0M0 disease, primary ADT alone will
Conclusion
HDPRT for N0M0 CRPC showed impressive local control rates with acceptable toxicity. Although extended survival without clinical evidence of disease progression was possible, prostate cancer-specific mortality remained the most frequent cause of death.
References (19)
- et al.
Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial
Lancet
(2010) - et al.
Palliative pelvic radiotherapy of symptomatic incurable prostate cancer - a systematic review
Radiother Oncol
(2014) - et al.
CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment
Semin Radiat Oncol
(2003) - et al.
Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial
Lancet
(2011) - et al.
Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial
Lancet
(2009) - et al.
Need for hospital care and palliative treatment for prostate cancer treated with noncurative intent
J Urol
(1995) - et al.
Split-course, high-dose palliative pelvic radiotherapy for locally progressive hormone-refractory prostate cancer
Int J Radiat Oncol Biol Phys
(2012) - et al.
Radiotherapy for regionally localised hormone refractory prostate cancer
Int J Radiat Oncol Biol Phys
(1995) - et al.
External beam radiotherapy for clinically localized hormone-refractory prostate cancer: clinical significance of Nadir prostate-specific antigen value within 12 months
Int J Radiat Oncol Biol Phys
(2009)