62_05
Brachytherapy For Early-Stage Disease: Treatment Techniques
Preplanned Transperineal Implantation Techniques
With the advent of transperineal CT and ultrasound-guided permanent prostatic implantation, the accuracy of isotope source placement has dramatically improved compared with older retropubic methods. The ultrasound-guided transperineal technique was initially described by Holm et al. (179) in 1983, and a large clinical experience was subsequently accumulated. This implantation technique evolved over the years into what is now known as the “Seattle Method,” which uses a computer-generated preplanned approach. The technique can be described as follows: TRUS imaging is obtained before the planned procedure to assess the prostate volume. A computerized plan is generated from the transverse ultrasound images, producing isodose distributions and the ideal location of seeds within the gland to deliver the prescription dose to the prostate. Several days to weeks later, the implantation procedure is performed. Needles are then placed under ultrasonographic guidance through a perineal template according to the coordinates determined by the preplan. Radioactive seeds are individually deposited in the needle with the aid of an applicator or with preloaded seeds on a semirigid strand containing the preplanned number of seeds. In the latter case, this is accomplished by stabilizing the needle obturator that holds the seed column in a fixed position while the needle is withdrawn slowly, depositing a row or series of seeds within the gland. One of the inherent advantages of a stranded seed approach is the reduction of seed migration and embolization to the lung compared with the use of free seeds. While the embolization rate for stranded seeds is generally reported at <1%, the rate ranges from 5% to 72% in patients implanted with loose seeds. Among patients implanted with loose seeds, usually fewer than 2% of the implanted seeds are likely to migrate. There is no evidence of any adverse effect caused by seed embolization (308).
In general most brachytherapists use a modified peripheral loading technique for permanent interstitial implantation. This approach has been advocated by the Seattle group after observing a high rate of urethral complications during the early years of their experience with a homogenous loading pattern, which resulted in high urethral doses. Careful evaluation of the preplan with attention to dose-volume histogram analyses of both the target and normal tissues is essential to ensure that the dose to the urethra and rectum are within tolerance ranges and the prescription dose is being delivered to the prostate target. In a recent multi-institutional analysis there remains a great deal of variability within preplans as to acceptable target volume, seed strength, dose homogeneity, treatment margins, and extracapsular seed placement, although prostate brachytherapy prescription doses are uniform (272).
Intraoperative Planning Techniques for Prostate Brachytherapy
With the current availability of sophisticated treatment planning programs that can rapidly generate highly conformal dose distributions in the operating room, intraoperative planning for prostate brachytherapy has emerged as an attractive method for prostate brachytherapy. Intraoperative planning takes advantage of the opportunity of using real-time measurements of the prostate during the procedure while preplanning is often performed several weeks before implantation, frequently under different conditions than the actual operative procedure. Subtle changes in the position of the ultrasound probe as well as the distortion of the prostate associated with needle placement and subsequent edema can result in profound changes in the shape of the gland compared with the preplanned prostatic contour. Consequently, intraoperative adjustments of seed and needle placements are frequently required and the postplan CT-based dosimetry does not always correspond to the idealized preplan. Commercially available systems can track the placement of deposited seeds within the gland, which can provide feedback to the operator for the need to make adjustments to ensure target coverage and maintain constrained doses to the urethra and rectum. Yet, limitations still exist with such programs in their inability to reliably track and capture the exact coordinates of all of the deposited seeds on ultrasound because of difficulties with individual seed recognition using current ultrasound imaging techniques.
At MSKCC, an intraoperative conformal optimization and planning for ultrasound-based transperineal implant (TPI) that obviates the need for preplanning has been used (459). This technique involves a sophisticated optimization system that incorporates acceptable dose ranges allowed within the target as well as dose constraints for the rectal wall and urethra. An ultrasound probe is positioned in the rectum, and the prostate and normal anatomies are identified. Needles are inserted through the perineal template at the periphery of the prostate. The prostate is subsequently scanned from apex to base, and these 0.5-cm images are transferred to the treatment planning system using a PC-based video capture system. On the computer monitor, the prostate contours and the urethra are digitized on each axial image. Needle positions are identified on each image, and their coordinates are incorporated into a genetic algorithm optimization program. After the optimization program identifies the optimal seed-loading pattern and the dose calculations are completed, isodose displays are superimposed on each transverse ultrasound image and carefully evaluated. Dose-volume histograms for the target volume, rectum, and urethra are also carefully assessed. If portions of the target volume are found to be underdosed or higher urethral doses on selected images are observed, appropriate adjustments are made with the deletion of a seed or insertion of a new needle positions, and revised isodose distributions are immediately generated. The entire planning process from the contouring of images to the generation of the seed-loading pattern requires approximately 10 minutes. Seeds are then loaded with a standard applicator. Figure 62.15 shows a postimplantation CT image used for dosimetric evaluation.
P.1464
Dose, Isotope, and Activity Considerations for Prostate Brachytherapy
In the retropubic implant era, 160 Gy was prescribed to a median peripheral dose, which assumed the prostate gland was in the configuration of a perfect ellipsoid. A reanalysis of the dosimetry of 125I performed by Task Group 43 revealed that the actual dose delivered for a 160-Gy implant was approximately 10% lower (291). At present, the commonly used dose for interstitial implantation is 144 Gy, prescribed to the isodose surface that completely encompasses the prostate as contoured from imaging studies. When 103Pd became available, a lower prescription dose was recommended for this isotope (115 Gy). However, based on a consensus (National Institutes of Standards and Technology 1999), the recommended prescription dose is approximately 10% higher or 125 Gy when 103Pd is used (36).
There are clear physical differences between these two isotopes. The half-life of 125I is 60 days, with a mean photon energy of 27 KeV and an initial dose rate of 7 cGy/hr. In contrast, the half-life of 103Pd is 17 days, with a mean photon energy of 21 KeV and an initial dose rate of 19 cGy/hr. Dosimetric analyses of treatment plans performed with either isotope have not revealed significant differences between them (109). Most retrospective reports (67,266) have failed to demonstrate any benefit in terms of local tumor control or long-term complications for either isotope. A randomized trial has been conducted comparing 125I with palladium-103 for the treatment of early-stage prostate cancer. To date, no difference in tumor control outcomes have been noted between the two arms of the study. Preliminary findings from this study have noted that patients treated with 103Pd had more intense radiation prostatitis in the first month after implantation, but recovered from their radiation-related symptoms sooner than 125I patients, consistent with palladium's shorter half-life (175).
Postimplantation Dosimetric Evaluation
Postimplantation dosimetric evaluation after prostate brachy-therapy is recommended as the standard assessment of the quality of permanent interstitial implantation used for the treatment of prostate cancer (286). The adequacy of the target coverage with the intended prescription doses is evaluated with surrogate parameters such as volume of the prostate treated to 100% of the prescription dose (V100) and the dose delivered to 90% of the prostate target (D90). These parameters have been shown by several investigators to be associated with biochemical relapse and posttreatment biopsy outcomes (19,325,391). Equally important, other parameters of implant quality measure the dose exposure to the urethra and rectum. These measurements have been correlated with postimplantation urinary and rectal-related toxicities (167,270,375,460). Commercial software is routinely available to determine the coverage of the prostate and dose to critical normal tissue structures. Isodose curves and dose-volume histograms produce a detailed analysis of the radiation dose distribution relative to the prostate and surrounding normal tissues. Postimplantation evaluation is performed on the day of the procedure or 30 days after the procedure. The latter time point may be preferable when prostate edema is less significant after the implant and would less likely underestimate the prostate coverage with the prescription dose.
Bice et al. (38) examined multiple dosimetric parameters obtained from 50 prostate implants performed in 5 institutions using preplanning techniques. In that analysis, the average V100 (percentage volume of the prostate exposed to the prescription dose) for the respective five centers in ascending order was 77.5%, 84.3%, 87%, 88.4%, and 94.5%. Average maximal rectal doses calculated for each of the centers were 195, 263, 271, 292, and 354 Gy. No data were reported regarding urethral doses, although it was suggested that implants performed at centers that achieved higher percentages of target coverage with the prescription dose noted a concomitant increase in the central urethral dose (reflected in a greater percentage of the target volume receiving >150% of the prescription dose).
Zelefsky et al. (459) reported dosimetric outcome for intraoperative planning. The median V100, V90, and D90 (dose delivered to 90% of the prostate target) values for the intraoperative 3D technique were 96%, 98%, and 116%, respectively. In contrast, the V100, V90, and D90 values for a CT preplan and an ultrasound manual approach were 86%, 89%, and 88%, respectively, and 88%, 92%, and 94%, respectively (intraoperative optimization vs. other techniques; p <.001). A multivariate analysis determined that the intraoperative 3D technique (compared with other techniques) was an independent predictor of improved target coverage for each dosimetric parameter analyzed (p <.001). The maximum and average urethral doses were significantly lower with the intraoperative 3D technique compared with the other techniques, whereas a modest increase in the average rectal dose was also observed with the intraoperative 3D approach. Others have also demonstrated improved dosimetric outcomes with intraoperative planning techniques (209,253,274,388). A summary of published dosimetric outcomes after brachytherapy based on postimplantation CT-based dosimetric outcomes is shown in Table 62.9.
Investigators from the Joint Center for Radiation Therapy have reported the feasibility and early outcomes of TPI using intraoperative MRI instead of ultrasonography to guide seed placement (191,405). The CTV was defined as the peripheral zones identified on MRI; thus, seed placement was limited to the peripheral zones of the prostate, while the central and transitional zones were not implanted. Initial dosimetric analyses indicated that the median percentage of the CTV receiving the prescription dose was 94%. The median urethral D10 (dose to 10% of the urethral volume) was 210 Gy (range, 124 to 280 Gy) or 131% of the prescription dose.
Postimplantation evaluation is considered an important quality assurance procedure for prostate brachytherapy and provides important feedback to the brachytherapist concerning the quality of the implant performed and what corrections need
P.1465
to be made to optimize target coverage to reduce normal tissue dosing. Postimplantation dosimetric parameters also reflect the dose delivered to the prostate and may predict the likelihood of long-term tumor control outcomes. Stock et al. (386) reported that, among patients with low-risk disease who had an optimal dose based on retrospective postimplantation dosimetry evaluation (D90 >140 Gy; n = 49), the PSA relapse-free survival at 8 years was 94%, compared to 75% for those who received lower dose levels (p = 0.02).
Combination External-Beam Radiation Therapy and Brachytherapy
Although monotherapy approaches (EBRT alone or seed implantation alone) are appropriate treatment options for favorable-risk patients, combination of these treatment modalities is generally considered a more suitable treatment option patients with higher-risk disease. When a combined-modality approach is chosen for a patient, various treatment schemes have been used to integrate the brachytherapy with the EBRT. In general, 45 to 50 Gy of EBRT is delivered using conventional or conformal-based techniques to the prostate and periprostatic tissues. If a low–dose-rate boost is used, the brachytherapy prescription dose has been 90 Gy for 103Pd implants and 110 Gy for 125I implants. In the absence of clinical trials comparing HDR brachytherapy boosts versus low–dose-rate boosts, or the optimal sequence of therapy (brachytherapy boost preceding EBRT or vice versa), or the optimal isotope to be used for combined-modality therapy, there is no definitive evidence demonstrating the superiority of a particular treatment strategy over another.
A phase III trial, Radiation Therapy Oncology Group (RTOG) 0232, has recently been activated that compares permanent source brachytherapy as monotherapy to the combination of external-beam treatment followed by brachytherapy for patients with intermediate-risk prostate cancer. The primary end point of this study is survival outcome, and secondary end points include PSA relapse-free survival, distant metastases-free survival, and quality of life end points. Eligibility criteria for this study include clinical stage T1c-T2b, Gleason <7 with PSA 10 to 20 ng/mL or Gleason 7 with a PSA <10 ng/mL. The American Urological Association voiding symptom score should be ≤15 and prostate volume <60 g.
High-Dose-Rate Brachytherapy Techniques
HDR brachytherapy has been used as the brachytherapy component in combination with EBRT for the treatment of prostate cancer (208,214,249,252). In general, for this approach patients undergo transperineal placement of afterloading catheters in the prostate under ultrasonographic guidance. After CT-based treatment planning, several high-dose fractions, ranging from 4 to 6 Gy each, are administered during an interval of 24 to 36 hours using 192Ir. This treatment is followed by supplemental EBRT directed to the prostate and periprostatic tissues to a dose of 45 to 50.4 Gy using conventional fractionation. The Beaumont group has used fractionated outpatient HDR brachytherapy boosts interdigitated throughout the course of EBRT (208,249). Real-time intraoperative planning from the intraoperative ultrasonographic image was performed and each of three HDR boost treatments was delivered in the operating room under anesthesia. A dose-escalation study was implemented to increase gradually the dose per fraction delivered with the HDR boost from 5.5 Gy for three fractions to 10.5 Gy for three fractions. Improved outcomes with higher HDR boost doses were observed compared with outcomes achieved using lower dose levels. More recently, these investigators have used HDR brachytherapy as monotherapy without the addition of EBRT. The fractionation regimen was 38 Gy delivered in four fractions, two times daily during 2 days, and early tolerance and tumor control outcomes have been promising (159).
HDR brachytherapy offers several potential advantages over other techniques. Taking advantage of an afterloading approach, the radiation oncologist and physicist can more easily optimize the delivery of radiation therapy to the prostate and compensate for potential regions of underdosage (“cold spots”) that may be present with permanent interstitial implantation. Further, this technique reduces radiation exposure to the radiation oncologist and others involved in the procedure compared with permanent interstitial implantation. Finally, HDR brachytherapy boosts may be radiobiologically more efficacious in terms of tumor cell kill for patients with increased tumor bulk or adverse prognostic features compared with low–dose-rate boosts such as 125I or 103Pd.
Preplanned Transperineal Implantation Techniques
With the advent of transperineal CT and ultrasound-guided permanent prostatic implantation, the accuracy of isotope source placement has dramatically improved compared with older retropubic methods. The ultrasound-guided transperineal technique was initially described by Holm et al. (179) in 1983, and a large clinical experience was subsequently accumulated. This implantation technique evolved over the years into what is now known as the “Seattle Method,” which uses a computer-generated preplanned approach. The technique can be described as follows: TRUS imaging is obtained before the planned procedure to assess the prostate volume. A computerized plan is generated from the transverse ultrasound images, producing isodose distributions and the ideal location of seeds within the gland to deliver the prescription dose to the prostate. Several days to weeks later, the implantation procedure is performed. Needles are then placed under ultrasonographic guidance through a perineal template according to the coordinates determined by the preplan. Radioactive seeds are individually deposited in the needle with the aid of an applicator or with preloaded seeds on a semirigid strand containing the preplanned number of seeds. In the latter case, this is accomplished by stabilizing the needle obturator that holds the seed column in a fixed position while the needle is withdrawn slowly, depositing a row or series of seeds within the gland. One of the inherent advantages of a stranded seed approach is the reduction of seed migration and embolization to the lung compared with the use of free seeds. While the embolization rate for stranded seeds is generally reported at <1%, the rate ranges from 5% to 72% in patients implanted with loose seeds. Among patients implanted with loose seeds, usually fewer than 2% of the implanted seeds are likely to migrate. There is no evidence of any adverse effect caused by seed embolization (308).
In general most brachytherapists use a modified peripheral loading technique for permanent interstitial implantation. This approach has been advocated by the Seattle group after observing a high rate of urethral complications during the early years of their experience with a homogenous loading pattern, which resulted in high urethral doses. Careful evaluation of the preplan with attention to dose-volume histogram analyses of both the target and normal tissues is essential to ensure that the dose to the urethra and rectum are within tolerance ranges and the prescription dose is being delivered to the prostate target. In a recent multi-institutional analysis there remains a great deal of variability within preplans as to acceptable target volume, seed strength, dose homogeneity, treatment margins, and extracapsular seed placement, although prostate brachytherapy prescription doses are uniform (272).
Intraoperative Planning Techniques for Prostate Brachytherapy
With the current availability of sophisticated treatment planning programs that can rapidly generate highly conformal dose distributions in the operating room, intraoperative planning for prostate brachytherapy has emerged as an attractive method for prostate brachytherapy. Intraoperative planning takes advantage of the opportunity of using real-time measurements of the prostate during the procedure while preplanning is often performed several weeks before implantation, frequently under different conditions than the actual operative procedure. Subtle changes in the position of the ultrasound probe as well as the distortion of the prostate associated with needle placement and subsequent edema can result in profound changes in the shape of the gland compared with the preplanned prostatic contour. Consequently, intraoperative adjustments of seed and needle placements are frequently required and the postplan CT-based dosimetry does not always correspond to the idealized preplan. Commercially available systems can track the placement of deposited seeds within the gland, which can provide feedback to the operator for the need to make adjustments to ensure target coverage and maintain constrained doses to the urethra and rectum. Yet, limitations still exist with such programs in their inability to reliably track and capture the exact coordinates of all of the deposited seeds on ultrasound because of difficulties with individual seed recognition using current ultrasound imaging techniques.
At MSKCC, an intraoperative conformal optimization and planning for ultrasound-based transperineal implant (TPI) that obviates the need for preplanning has been used (459). This technique involves a sophisticated optimization system that incorporates acceptable dose ranges allowed within the target as well as dose constraints for the rectal wall and urethra. An ultrasound probe is positioned in the rectum, and the prostate and normal anatomies are identified. Needles are inserted through the perineal template at the periphery of the prostate. The prostate is subsequently scanned from apex to base, and these 0.5-cm images are transferred to the treatment planning system using a PC-based video capture system. On the computer monitor, the prostate contours and the urethra are digitized on each axial image. Needle positions are identified on each image, and their coordinates are incorporated into a genetic algorithm optimization program. After the optimization program identifies the optimal seed-loading pattern and the dose calculations are completed, isodose displays are superimposed on each transverse ultrasound image and carefully evaluated. Dose-volume histograms for the target volume, rectum, and urethra are also carefully assessed. If portions of the target volume are found to be underdosed or higher urethral doses on selected images are observed, appropriate adjustments are made with the deletion of a seed or insertion of a new needle positions, and revised isodose distributions are immediately generated. The entire planning process from the contouring of images to the generation of the seed-loading pattern requires approximately 10 minutes. Seeds are then loaded with a standard applicator. Figure 62.15 shows a postimplantation CT image used for dosimetric evaluation.
P.1464
Dose, Isotope, and Activity Considerations for Prostate Brachytherapy
In the retropubic implant era, 160 Gy was prescribed to a median peripheral dose, which assumed the prostate gland was in the configuration of a perfect ellipsoid. A reanalysis of the dosimetry of 125I performed by Task Group 43 revealed that the actual dose delivered for a 160-Gy implant was approximately 10% lower (291). At present, the commonly used dose for interstitial implantation is 144 Gy, prescribed to the isodose surface that completely encompasses the prostate as contoured from imaging studies. When 103Pd became available, a lower prescription dose was recommended for this isotope (115 Gy). However, based on a consensus (National Institutes of Standards and Technology 1999), the recommended prescription dose is approximately 10% higher or 125 Gy when 103Pd is used (36).
There are clear physical differences between these two isotopes. The half-life of 125I is 60 days, with a mean photon energy of 27 KeV and an initial dose rate of 7 cGy/hr. In contrast, the half-life of 103Pd is 17 days, with a mean photon energy of 21 KeV and an initial dose rate of 19 cGy/hr. Dosimetric analyses of treatment plans performed with either isotope have not revealed significant differences between them (109). Most retrospective reports (67,266) have failed to demonstrate any benefit in terms of local tumor control or long-term complications for either isotope. A randomized trial has been conducted comparing 125I with palladium-103 for the treatment of early-stage prostate cancer. To date, no difference in tumor control outcomes have been noted between the two arms of the study. Preliminary findings from this study have noted that patients treated with 103Pd had more intense radiation prostatitis in the first month after implantation, but recovered from their radiation-related symptoms sooner than 125I patients, consistent with palladium's shorter half-life (175).
Postimplantation Dosimetric Evaluation
Postimplantation dosimetric evaluation after prostate brachy-therapy is recommended as the standard assessment of the quality of permanent interstitial implantation used for the treatment of prostate cancer (286). The adequacy of the target coverage with the intended prescription doses is evaluated with surrogate parameters such as volume of the prostate treated to 100% of the prescription dose (V100) and the dose delivered to 90% of the prostate target (D90). These parameters have been shown by several investigators to be associated with biochemical relapse and posttreatment biopsy outcomes (19,325,391). Equally important, other parameters of implant quality measure the dose exposure to the urethra and rectum. These measurements have been correlated with postimplantation urinary and rectal-related toxicities (167,270,375,460). Commercial software is routinely available to determine the coverage of the prostate and dose to critical normal tissue structures. Isodose curves and dose-volume histograms produce a detailed analysis of the radiation dose distribution relative to the prostate and surrounding normal tissues. Postimplantation evaluation is performed on the day of the procedure or 30 days after the procedure. The latter time point may be preferable when prostate edema is less significant after the implant and would less likely underestimate the prostate coverage with the prescription dose.
Bice et al. (38) examined multiple dosimetric parameters obtained from 50 prostate implants performed in 5 institutions using preplanning techniques. In that analysis, the average V100 (percentage volume of the prostate exposed to the prescription dose) for the respective five centers in ascending order was 77.5%, 84.3%, 87%, 88.4%, and 94.5%. Average maximal rectal doses calculated for each of the centers were 195, 263, 271, 292, and 354 Gy. No data were reported regarding urethral doses, although it was suggested that implants performed at centers that achieved higher percentages of target coverage with the prescription dose noted a concomitant increase in the central urethral dose (reflected in a greater percentage of the target volume receiving >150% of the prescription dose).
Zelefsky et al. (459) reported dosimetric outcome for intraoperative planning. The median V100, V90, and D90 (dose delivered to 90% of the prostate target) values for the intraoperative 3D technique were 96%, 98%, and 116%, respectively. In contrast, the V100, V90, and D90 values for a CT preplan and an ultrasound manual approach were 86%, 89%, and 88%, respectively, and 88%, 92%, and 94%, respectively (intraoperative optimization vs. other techniques; p <.001). A multivariate analysis determined that the intraoperative 3D technique (compared with other techniques) was an independent predictor of improved target coverage for each dosimetric parameter analyzed (p <.001). The maximum and average urethral doses were significantly lower with the intraoperative 3D technique compared with the other techniques, whereas a modest increase in the average rectal dose was also observed with the intraoperative 3D approach. Others have also demonstrated improved dosimetric outcomes with intraoperative planning techniques (209,253,274,388). A summary of published dosimetric outcomes after brachytherapy based on postimplantation CT-based dosimetric outcomes is shown in Table 62.9.
Investigators from the Joint Center for Radiation Therapy have reported the feasibility and early outcomes of TPI using intraoperative MRI instead of ultrasonography to guide seed placement (191,405). The CTV was defined as the peripheral zones identified on MRI; thus, seed placement was limited to the peripheral zones of the prostate, while the central and transitional zones were not implanted. Initial dosimetric analyses indicated that the median percentage of the CTV receiving the prescription dose was 94%. The median urethral D10 (dose to 10% of the urethral volume) was 210 Gy (range, 124 to 280 Gy) or 131% of the prescription dose.
Postimplantation evaluation is considered an important quality assurance procedure for prostate brachytherapy and provides important feedback to the brachytherapist concerning the quality of the implant performed and what corrections need
P.1465
to be made to optimize target coverage to reduce normal tissue dosing. Postimplantation dosimetric parameters also reflect the dose delivered to the prostate and may predict the likelihood of long-term tumor control outcomes. Stock et al. (386) reported that, among patients with low-risk disease who had an optimal dose based on retrospective postimplantation dosimetry evaluation (D90 >140 Gy; n = 49), the PSA relapse-free survival at 8 years was 94%, compared to 75% for those who received lower dose levels (p = 0.02).
Combination External-Beam Radiation Therapy and Brachytherapy
Although monotherapy approaches (EBRT alone or seed implantation alone) are appropriate treatment options for favorable-risk patients, combination of these treatment modalities is generally considered a more suitable treatment option patients with higher-risk disease. When a combined-modality approach is chosen for a patient, various treatment schemes have been used to integrate the brachytherapy with the EBRT. In general, 45 to 50 Gy of EBRT is delivered using conventional or conformal-based techniques to the prostate and periprostatic tissues. If a low–dose-rate boost is used, the brachytherapy prescription dose has been 90 Gy for 103Pd implants and 110 Gy for 125I implants. In the absence of clinical trials comparing HDR brachytherapy boosts versus low–dose-rate boosts, or the optimal sequence of therapy (brachytherapy boost preceding EBRT or vice versa), or the optimal isotope to be used for combined-modality therapy, there is no definitive evidence demonstrating the superiority of a particular treatment strategy over another.
A phase III trial, Radiation Therapy Oncology Group (RTOG) 0232, has recently been activated that compares permanent source brachytherapy as monotherapy to the combination of external-beam treatment followed by brachytherapy for patients with intermediate-risk prostate cancer. The primary end point of this study is survival outcome, and secondary end points include PSA relapse-free survival, distant metastases-free survival, and quality of life end points. Eligibility criteria for this study include clinical stage T1c-T2b, Gleason <7 with PSA 10 to 20 ng/mL or Gleason 7 with a PSA <10 ng/mL. The American Urological Association voiding symptom score should be ≤15 and prostate volume <60 g.
High-Dose-Rate Brachytherapy Techniques
HDR brachytherapy has been used as the brachytherapy component in combination with EBRT for the treatment of prostate cancer (208,214,249,252). In general, for this approach patients undergo transperineal placement of afterloading catheters in the prostate under ultrasonographic guidance. After CT-based treatment planning, several high-dose fractions, ranging from 4 to 6 Gy each, are administered during an interval of 24 to 36 hours using 192Ir. This treatment is followed by supplemental EBRT directed to the prostate and periprostatic tissues to a dose of 45 to 50.4 Gy using conventional fractionation. The Beaumont group has used fractionated outpatient HDR brachytherapy boosts interdigitated throughout the course of EBRT (208,249). Real-time intraoperative planning from the intraoperative ultrasonographic image was performed and each of three HDR boost treatments was delivered in the operating room under anesthesia. A dose-escalation study was implemented to increase gradually the dose per fraction delivered with the HDR boost from 5.5 Gy for three fractions to 10.5 Gy for three fractions. Improved outcomes with higher HDR boost doses were observed compared with outcomes achieved using lower dose levels. More recently, these investigators have used HDR brachytherapy as monotherapy without the addition of EBRT. The fractionation regimen was 38 Gy delivered in four fractions, two times daily during 2 days, and early tolerance and tumor control outcomes have been promising (159).
HDR brachytherapy offers several potential advantages over other techniques. Taking advantage of an afterloading approach, the radiation oncologist and physicist can more easily optimize the delivery of radiation therapy to the prostate and compensate for potential regions of underdosage (“cold spots”) that may be present with permanent interstitial implantation. Further, this technique reduces radiation exposure to the radiation oncologist and others involved in the procedure compared with permanent interstitial implantation. Finally, HDR brachytherapy boosts may be radiobiologically more efficacious in terms of tumor cell kill for patients with increased tumor bulk or adverse prognostic features compared with low–dose-rate boosts such as 125I or 103Pd.
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