Salvage Brachytherapy After External-Beam Irradiation for Prostate Cancer

Dr. Beyer provides an insight ful and balanced approach to the indications for salvage prostate brachytherapy after externalbeam radiotherapy failure. As he points out, the challenge for the clinician contemplating local salvage therapy to address biochemical failure is to determine whether the biochemical relapse represents local relapse only or systemic disease. Local salvage treatment in a patient with micrometastatic disease would have no appreciable impact on disease-free survival and is more likely to be associated with significant potential morbidity. Unfortunately, with the current lack of reliable molecular markers or sensitive imaging modalities, it is impossible to determine with certainty the source of a biochemical relapse in most settings. Identifying Patients With Isolated Local Relapsing Disease
Patients with tumor characteristics such as initial Gleason scores 8 to 10 or initially high prostate-specific antigen levels-consistent with an increased likelihood of extraprostatic disease-are not the optimal candidates for salvage brachytherapy due to expected poor outcomes in these patients. In addition to the fact that these patients have a greater risk of extracapsular disease, they are also as likely to have a larger volume of disease, and brachytherapy alone is often insufficient treatment. It is well known that higher radiation doses are critical in the treatment of patients with intermediate- and unfavorable- risk disease, so one would expect that high radiation doses are as important for eradicating locally recurrent disease. I have often wondered, therefore, why we should realistically expect local tumor control with a salvage low-dose-rate implant delivering a dose of only 120 Gy or 144 Gy. On the other hand, higher doses in the salvage setting cannot be given without impunity when radiotherapy has been previously given to the same region. It may be conceptually appealing to deliver an escalated radiation dose with a combination interstitial implant and a more modest dose of external-beam radiotherapy in the recurrent setting, yet there is minimal information to support the safety of such a salvage approach. The combination of both therapies in the setting of prior treatment could be a prescription for disaster and should only be done in the hands of experienced practitioners. Even in experienced hands, this form of dose escalation is essentially unproven as far as toxicity is concerned and should only be conducted in the context of a clinical trial. It is important to exercise caution when considering salvage brachytherapy, because dose escalation with external-beam radiotherapy has become common. The 1999 Patterns of Care survey showed a significant increase among radiation oncologists who deliver doses > 72 Gy, compared to the prior survey conducted in 1993.[1] The published literature includes a report on a small cohort of patients with salvage brachytherapy who previously had been irradiated to dose levels of 70 Gy or less. If previous dose levels ≥ 75 Gy were used for the patient being considered for salvage therapy, the expected morbidity of salvage brachytherapy after external-beam radiotherapy failure remains to be determined. We don't know how well-tolerated a salvage implant will be for these patients. The Potential of Functional Imaging
Enhanced imaging techniques to localize intraprostatic recurrent disease hold great promise for improving the therapeutic ratio of salvage brachytherapy. Magnetic resonance (MR) spectroscopy can localize disease within the prostate after failed external-beam radiotherapy and may allow clinicians to dose-paint abnormal regions within the clinical target volume and escalate the radiation doses to these areas, while potentially minimizing the dose to normal tissues previously irradiated. We and others have reported on using information from MR imaging and MR spectroscopy with intraoperatively planned conformal brachytherapy to dose-escalate intraprostatic tumor deposits to 150% of prescription dose (and higher) for patients with nonrecurrent prostate cancer as their primary therapy.[2,3] Ellis and coinvestigators[ 4] recently reported excellent results in 80 patients treated with brachytherapy, where radioimmunoscintigraphy with indium-111 was used to dose-escalate abnormal regions within the gland to 150% of the prescription dose. These approaches adapted in the salvage setting may represent an attractive approach in the future to effectively minimize dose to the rectum and the urethra. Although relapsing disease is likely be multifocal in nature and such patients may not be ideal candidates for such approaches, other scenarios can be envisioned in which a dominant abnormality in the prostate could receive higher doses, allowing for the opportunity to spare the previously irradiated rectum and urethra and to reduce the potential morbidity of therapy. Conclusions
Emerging technologies and improvements in brachytherapy treatment planning will pave the way for salvage brachytherapy to be delivered with potentially less toxicity and improved tumor- control rates. Selection of patients with isolated local relapse disease will remain critical, and improved imaging modalities and more precise molecular markers will be required to more accurately determine the source of a biochemical relapse. In the meantime, it may be prudent to offer salvage brachytherapy to highly selected patients with biopsy-proven local recurrence, a low likelihood of micrometastatic disease, and no significant proctitis or urethritis after initial radiotherapy. I wouldn't be surprised if hundreds of patients actually have been treated with salvage radiotherapy by practitioners around the country, but we can only make statements about the efficacy and safety of salvage therapy based on the published results in fewer than 100 patients. We need prospective clinical trials to clarify the efficacy and morbidity of this approach, so we may better advise our patients about the best intervention to treat their relapsing disease and how it would impact upon their quality of life.