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Salvage Brachytherapy After External-Beam Irradiation for Prostate Cancer

Salvage Brachytherapy After External-Beam Irradiation for Prostate Cancer

Dr. Beyer has done a good job of summarizing the issues concerning the use of brachytherapy as a salvage modality to treat radiation therapy failures. This will become an issue of greater importance as we continue to diagnose and treat younger and younger patients with prostate cancer. This trend can be primarily attributed to the success of prostate-specific antigen (PSA) screening. With younger patients opting for radiation treatment, the number of patients at potential risk for failure and hence potential candidates for salvage brachytherapy will increase. This, coupled with the stage migration toward early-stage, lower- PSA disease, may result in an increasing population of patients with perhaps more curable recurrent disease. Patient Selection
Although a greater number of patients may be considering this procedure, physicians must pay great attention to patient selection when evaluating a potential candidate. As Dr. Beyer rightly points out, not all patients with a rising PSA following definitive external- beam irradiation are good candidates for local salvage therapy. The dilemma that still exists is the selection of patients with truly localized disease without the presence of microscopic disseminated disease. More aggressive work-ups are needed for these patients. Newer modalities with which to detect extraprostatic disease will probably play a more important role in this subset of patients. Ultrasound-guided seminal vesicle imaging is a good way to detect patients with seminal vesicle recurrences.[1] These patients are also at a very high risk for extracapsular disease and/or nodal metastases and are not ideal candidates for salvage brachytherapy. In addition, newer methods of examining lymph node metastases will become increasingly important. Patients may fail radiation therapy, in part, because they harbor more aggressive prostate cancer than what was predicted based on pretreatment disease parameters. These patients are also at greater risk of having lymph node metastases. Lymph node-positive patients are not ideal candidates for salvage brachytherapy. The use of highly lymphotropic superparamagnetic nanoparticles in conjunction with high-resolution magnetic resonance imaging has been shown to be highly predictive for lymph node metastases.[ 2] In addition, laparoscopic procedures can make lymph node sampling a less invasive procedure than open surgery.[1] Research is also being conducted to assess the role of reverse-transcriptase-polymerase chain reaction assays for PSA in detecting micrometastases in these nodes.[3] All of these newer procedures can be potentially useful in the selection of node-negative patients for salvage brachytherapy. Treatment Considerations
Once a patient has been properly selected for this approach, the treatment itself becomes the next critical issue. Because patients are receiving radiation from their implant in the setting of a previously irradiated prostate and normal tissues, technique and dose become critical in reducing the risk of treatment-related morbidity. As Dr. Beyer points out, morbidity has decreased with greater experience in salvage brachytherapy. Although refinements in technique have lead to a reduction in morbidity, most retrospective series contain a small number of patients with serious complications, including radiation proctitis, incontinence, and fistulas. In order to reduce these complications, several important issues must be examined. The first is radiation dose. The delivery of a full dose that is normally given for a de novo implant is probably too risky, given the prior dose of external-beam irradiation that the patient has received. Lower doses such as those mentioned by Dr. Beyer make more sense in this setting. Because less than full doses are to be delivered, the risk of delivering inadequate doses of radiation exists. One method of potentially compensating for these lower doses is to administer both neoadjuvant and concomitant hormonal therapy. Hormonal therapy has shown beneficial effects when combined with external-beam irradiation in the setting of newly diagnosed locally advanced prostate cancer.[4-8] Certainly, recurrent prostate cancer represents another variant of aggressive prostate cancer. Based on randomized trials of external- beam radiotherapy, it makes sense to use hormonal therapy with its potential additive or synergistic effects with radiation in this setting. We have found that with proper patient selection and the use of hormonal therapy combined with salvage brachytherapy, the best PSA control rates can be obtained. In our series of 24 patients treated with salvage brachytherapy, all patients not receiving hormonal therapy as part of their treatment developed a recurrence, compared to only 26% of those receiving hormonal therapy (P = .01).[9] Therapeutic Technique
Other critical therapeutic issues concern technique and experience. Salvage brachytherapy should not be undertaken by practitioners who are relatively inexperienced with the procedure; only physicians who have mastered primary cases should attempt salvage procedures. As to technique, seeds placed too close to the rectal wall or too close to the urethra can lead to serious complications. Our analysis of rectal bleeding in patients receiving iodine-125 prostate implants found a close relationship between the amount of rectal tissue receiving the prescription dose and the development of grade 2 proctitis.[10] The threshold for developing brachytherapy- induced proctitis and the more serious rectal ulcer or fistula is probably much lower in a patient who has received prior external-beam irradiation than in a patient receiving an implant de novo. One method of minimizing these problems is to use an intraoperative dosimetry and planning system.[11] This enables the physician to view the procedure live and monitor seed deposition with the aid of ultrasound and a computer-generated dosimetry program. Using such a system may allow for more precise seed placement and better control of the delivered dose to the rectum and urethra. In conclusion, by focusing on proper selection and therapeutic approach, we can hopefully improve treatment outcomes for this growing population of patients with recurrent prostate cancer.

Disclosures

The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References

1. Stock RG, Stone NN, Iannuzzi C, et al: Seminal vesicle biopsy and laparoscopic pelvic lymph node dissection: Implications for patient selection in the radiotherapeutic management of prostate cancer. Int J Radiat Oncol Biol Phys 33:815-821, 1995.
2. Harisinghani MG, Barentsz J, Hahn PF, et al: Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491-2499, 2003.
3. Ferrari AC, Stone NN, Eyler JN, et al: Molecular staging of pelvic lymph nodes increases the detection of micrometastases in high-risk localized prostate cancer patients. J Natl Cancer Inst 89:1498-1504, 1997.
4. Bolla M, Gonzalez D, Warde P, et al: Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 337:295- 300, 1997.
5. Hanks GE, Pajak TF, Porter A, et al: Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: The Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol 21:3972-3978, 2003.
6. Pilepilch MV, Krall JM, Al-Sarraf, et al: Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: A randomized comparative trial of the Radiation Therapy Oncology Group. Urology 45:616- 623, 1995.
7. Pilepilch MV, Kaplan R, Byhardt RW, et al: Phase III trial of androgen suppression using goserelin in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy: Report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol 15:1013-1021, 1997.
8. Laverdiere J, Gomez JL, Cusan L, et al: Beneficial effect of combination therapy administered prior and following external beam radiation therapy in localized prostate cancer. Int J Radiat Oncol Biol Phys 37:247-252, 1997.
9. Obedian E, Stone NN, Hong SM, et al: Salvage brachytherapy for locally recurrent prostate carcinoma after definitive radiation therpy: Which patients benefit the most. Int J Radiat Oncol Biol Phys 51:319, 2001.
10. Snyder KM, Stock RG, Hong SM, et al: Defining the risk of developing grade 2 proctitis following I-125 prostate brachytherapy using a rectal dose volume histogram analysis. Int J Radiat Oncol Biol Phys 50:335- 341, 2001.
11. Stock RG, Stone NN, Lo YC: Intraoperative dosimetric representation of the realtime ultrasound guided prostate implant. Tech Urol 6:95-98, 2000.
 
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