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© 2000 American Society for Clinical Oncology Matched-Pair Analysis of Conformal High–Dose-Rate Brachytherapy Boost Versus External-Beam Radiation Therapy Alone for Locally Advanced Prostate CancerFrom the Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI. Address reprint requests to Alvaro A. Martinez, MD, FACR, Department of Radiation Oncology, William Beaumont Hospital, 3601 W Thirteen Mile Rd, Royal Oak, MI 48073; email amartinez{at}beaumont .edu.
PURPOSE: We performed a matched-pair analysis to compare our institution’s experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high–dose-rate (HDR) brachytherapy boosts (EBRT + HDR).
MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P < .001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P < .001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.
THE OPTIMAL TREATMENT for locally advanced prostate cancer remains undefined.1 External-beam radiation therapy (EBRT) has been considered the standard curative treatment, but long-term cure rates have been suboptimal. Recent studies have indicated potential improvement in treatment outcome using either high-dose three-dimensional conformal EBRT,2-7 neutrons,8 EBRT in combination with androgen deprivation,9-12 or EBRT in combination with ultrasound-guided transperineal interstitial brachytherapy with either permanent seeds13-15 or temporary high–dose-rate (HDR) implants.16-22 Due to multiple factors, the interpretation of the published results of these various newer treatment techniques has been complicated. The gradual natural history of prostate cancer requires lengthy follow-up for adequate determination of clinical outcome and survival. Therefore, studies must often focus on earlier end points, such as the prostate-specific antigen (PSA) nadir level and biochemical control. Although these end points have been significantly associated with clinical outcome and survival,23-25 the wide variety of biochemical failure definitions further confuses the issue.25-28 Also, because feasibility and toxicity must first be addressed with any new treatment, the majority of studies have been published as retrospective or prospective single-arm studies with potential selection bias. In addition, there are multiple critical prognostic factors in prostate cancer that must be controlled for to allow adequate comparison between institutions and treatment approaches.
In an attempt to improve treatment outcome in patients with locally advanced prostate cancer, a prospective dose-escalating trial using EBRT with conformal interstitial HDR brachytherapy boosts (EBRT + HDR) was initiated for patients with clinical stage T2b to T3c, N0M0 prostate cancer29 in 1991. Later, this protocol was modified to also include stage T1c to T2a patients with a pretreatment PSA level
From November 1991 through May 1998, 168 patients with locally advanced prostate adenocarcinoma were prospectively treated in a dose-escalating clinical trial with EBRT in combination with HDR brachytherapy at William Beaumont Hospital, Royal Oak, Michigan. All patients gave informed consent before protocol entry. Patients with any of the following characteristics were eligible for study entry: pretreatment PSA level  10.0 ng/mL, Gleason score 7, or clinical stage T2b to T3c.
From January 1987 through December 1997, 1,109 patients with prostate adenocarcinoma were treated with definitive EBRT alone at our institution. Each of the EBRT + HDR patients was randomly matched with a single unique EBRT-alone patient. The RANDOMIZE statement was used with the RND function within Microsoft Visual Basic (Microsoft Corporation, Redmond, WA) to generate random numbers between 1 and 1,109. Patients were matched according to the following criteria: (1) same pretreatment PSA subgroup ( The initial evaluation for all patients included a history and physical examination including a digital rectal examination, a chest x-ray, and routine serum laboratory studies (complete blood cell count and biochemistry panel including an alkaline phosphatase level). Pretreatment PSA levels were recorded for all patients. The Tandem-R monoclonal method (Hybridtech, Inc, San Diego, CA) or the Abbott microparticle immunoassay (IMX, Abbott Laboratories, Chicago, IL) was used to measure pretreatment serum PSA. Pathologic analyses of biopsy tissue as well as assignment of Gleason scores were performed within our institution. Radioisotope bone scans and computed tomography (CT) scans of the pelvis were performed to rule out metastatic disease. Those patients with abnormalities on bone scan underwent follow-up plain radiographs for further evaluation. All patients had American Joint Committee on Cancer (AJCC) clinical stage I to III (T1 to T3, N0M0) adenocarcinoma of the prostate at presentation.29
Our EBRT + HDR treatment technique has been previously described.22,30,31 Briefly, the pelvis was irradiated with 10-MV or 18-MV photons to a median dose of 46.0 Gy in 1.8- to 2.0-Gy fractions using a four-field technique. The prostate was outlined using a urethrogram, bladder contrast, and a rectal marker. All patients had pretreatment pelvic CT scans to assist in defining prostate and normal tissue volumes. Pelvic EBRT was supplemented with ultrasound-guided transperineal interstitial iridium-192 (192Ir) HDR implants. From 1991 to 1995, all patients underwent three interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. Pelvic EBRT was not given on the days of HDR brachytherapy treatment. After October 1995, all patients underwent two interstitial implants during the first and third weeks of pelvic EBRT. The implant procedure was performed under spinal anesthesia with the patient in the lithotomy position. A 7.5-MHz biplanar transrectal ultrasound (TRUS) probe was carefully positioned parallel to the prostatic urethra. The apex and base of the prostate were identified using transverse and sagittal TRUS images. The length of the prostate and corresponding treatment length was considered the distance from the base to the apex. The prostate was contoured at 5 mm intervals from base to apex on transverse TRUS images. The urethra was mapped on each 5 mm transverse image as well. The transverse image with the largest cross-sectional prostate area was considered the reference plane. The planning target volume (PTV) was "cylindrically-shaped" with transverse cross-sections of the treatment volume corresponding to the shape and size of the reference plane. The "cylindrically-shaped" treatment volume extended from the base to the apex. Desired needle positions within the reference plane were determined intraoperatively using interactive in-house software.32-34 Needles were placed parallel to the TRUS probe and urethra via a template mounted to the TRUS probe. After placement of all needles, cystoscopy was performed to verify that no needles penetrated the urethral or bladder mucosa. After instilling bladder contrast, C-arm fluoroscopy was also performed to verify appropriate needle position in reference to the bladder mucosa. Before final dosimetric calculation, all needle and urethral positions were recaptured. Treatment was delivered via the Nucletron microSelectron-HDR 192Ir remote afterloading system (Nucletron, BV, Veenendaal, the Netherlands). All dosimetric calculations were performed intraoperatively, and the final treatment plan was generated with the Nucletron Planning System (Nucletron, BV). Treatment was optimized using standard geometric optimization.32,35 On each transverse TRUS image, the 100% isodose line encompassed the contoured PTV without margins. For those patients who underwent three interstitial implants, the dose to this treatment volume was escalated from 5.50 Gy for each implant initially, to 6.00 Gy subsequently, and finally to 6.50 Gy. Subsequently, patients who underwent two implants received 8.25 Gy in each implant initially, then 8.75 Gy, 9.50 Gy, and finally 10.50 Gy. The breakdown of implant dose for the 161 patients was as follows: 5.50 Gy x 3, 26 patients (16%); 6.00 Gy x 3, 19 patients (12%); 6.50 Gy x 3, 27 patients (17%); 8.25 Gy x 2, 28 patients (17%); 8.75 Gy x 2, 24 patients (15%); 9.50 Gy x 2, 33 patients (20%); and 10.50 Gy x 2, four patients (2%). The urethral dose was calculated on each 5-mm transverse image and was generally limited to For the EBRT-alone patients, our standard EBRT technique has been previously described.23,28,37,38 Briefly, the prostate was irradiated with 6- to 18-MV photons to a median dose of 50.4 Gy (range, 45.0 to 50.4 Gy) in 1.8 to 2.0 Gy fractions using a four-field or arc technique. This was followed by a supplemental bilateral-arc or four-field boost (range, 16.0 to 25.4 Gy) for a median total dose of 66.6 Gy (range, 59.4 to 70.4 Gy). The prostate field was outlined using a urethrogram, bladder contrast, and a rectal marker. One hundred twenty-nine patients (80%) had pretreatment pelvic CT scans to assist in defining prostate and normal tissue volumes. Since 1992, patients with locally advanced disease were offered participation in the EBRT + HDR dose-escalation study. Those patients who refused, did not qualify, or were not appropriate candidates according to the treating physician’s judgment were treated according to our standard EBRT-alone policy. No patient in either treatment group received hormonal therapy either before, during, or after RT unless local or distant failure was documented or the post–radiation therapy (RT) PSA profile was indicative of biochemical failure on the basis of the physician’s judgment. Patients who required hormonal therapy to reduce the prostatic volume were not included in this analysis. Patients were seen in follow-up 1 month after completion of RT and were evaluated every 3 to 6 months thereafter; serum PSA level was measured with each evaluation. Patients frequently alternated follow-up visits between their urologist and radiation oncologist. For all patients, routine serial posttreatment PSA levels were obtained. Before May 1996, the Tandem-R monoclonal method was used to measure serum PSA levels. Normal values with this method ranged from less than 0.4 to 4.0 ng/mL, with the lower limit of detection at 0.4 ng/mL. In May 1996, the Tandem-R monoclonal method was replaced with the Abbott microparticle immunoassay. This assay demonstrated an improved detection sensitivity of 0.1 ng/mL, with a resultant normal range from less than 0.1 to 4.0 ng/mL. Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel statement.27 Three consecutive increases in PSA after reaching the PSA nadir constituted biochemical failure. The date of failure was the midpoint between the nadir and the first of the three increases in PSA. If PSA values were repeated in the midst of three PSA increases (eg, 0.4, 0.5, 0.5, 0.6, 0.6, 0.7), patients were still considered to have experienced biochemical failure. However, if a decrease in PSA occurred, a patient must have then had three subsequent PSA increases before he was judged to have experienced biochemical failure. If hormonal therapy was administered to patients before meeting criteria for failure, then patients were considered to have experienced biochemical failure at the time of initiation of hormonal therapy. Abnormalities identified on follow-up evaluation (eg, CT scan, bone scan with x-ray correlation, chest x-ray) that were clearly consistent with local failure or distant metastasis constituted clinical failure. Pathologic tissue diagnosis was not required. Overall survival reflected all deaths, cancer-related or otherwise. Disease-free survival incorporated either biochemical failure, clinical failure, or death resulting from any cause. Cause-specific survival was based on deaths that could be attributed to prostate cancer. In those cases for which the cause of death was unclear, death was considered to have resulted from prostate cancer if clinically evident prostate cancer (with a detectable PSA level) was present at the time of death. PSA follow-up was defined as the interval from completion of RT to the date of the most recent serum PSA level. Clinical follow-up was defined as the interval from completion of RT to the date of last known patient contact.
Actuarial results were calculated by the Kaplan-Meier method.39 When calculating biochemical control, controlled patients were censored at the date of their last known PSA value. The association of clinical, pathologic, and treatment-related variables with any given event was analyzed using Cox regression or Fisher’s exact test (two-tailed) for categorical variables and Cox regression for continuous variables.40 The student’s unpaired t test was used to determine the significance of the difference between two sample means. The statistical significance of differences between actuarial curves was calculated with the log-rank test.41 Multivariate analysis was performed using the Cox proportional hazards model.40 A P value of The median PSA follow-up was 2.5 years (range, 0.3 to 7.2 years) for EBRT + HDR patients and 2.5 years (range, 0.3 to 7.4 years) for EBRT-alone patients. The median clinical follow-up was 2.8 years (range, 0.4 to 7.2 years) for EBRT + HDR patients and 3.1 years (range, 0.4 to 7.7 years) for EBRT-alone patients. A total of 83 patients (26%) have been followed-up for a minimum of 5 years, whereas 44 patients (14%) have been followed-up for more than 6 years.
Patient Characteristics Table 1 lists median values for various clinical, pathologic, and treatment-related characteristics in each treatment group. The median pretreatment PSA level was 9.9 ng/mL, and the median biopsy Gleason score was 7 in each treatment group. Although patients receiving EBRT + HDR had a trend toward higher clinical T stage (P = .07), the median T stage was T2b in each treatment group. The breakdown of EBRT + HDR patients by T-stage subcategory was as follows: T1c, 11%; T2a, 11%; T2b, 29%; T2c, 35%; T3a, 7%; T3b, 1%; and T3c, 5%. For EBRT alone, the breakdown was as follows: T1c, 11%; T2a, 29%; T2b, 21%; T2c, 25%; T3a, 7%; T3b, 1%; and T3c, 5%. The median age at diagnosis was 74 years for EBRT-alone patients and 69 years for EBRT + HDR patients (P < .001; t test). In the 182 patients (57%) with available information on the number of biopsy cores sampled and the number found to be positive, a median of 50% of cores contained malignancy for EBRT + HDR patients versus 29% for EBRT-alone patients (P = .001). Assuming a tumor alpha/beta ratio of 1.5 Gy,42 the median BED1.5 (equivalent in 2.0-Gy fractions) was 92.0 Gy (range, 78.0 to 118.0 Gy) for EBRT + HDR versus 63.5 Gy (range, 56.6 to 76.9 Gy) for EBRT alone.
Biochemical Outcome Patients treated with EBRT + HDR demonstrated a significantly lower PSA nadir (0.4 v 1.1 ng/mL; P = .009) and achieved nadir at a longer time interval after RT (1.5 v 1.0 years; P < .001) than patients treated with EBRT alone. Based on the American Society for Therapeutic Radiology and Oncology Consensus Panel definition of biochemical failure, the 5-year actuarial biochemical control rate was 67% for EBRT + HDR versus 44% for EBRT alone (P < .001; Table 2; Fig 1). A total of 31 EBRT + HDR patients experienced biochemical failure at a median interval of 1.7 years (range, 0.3 to 3.8 years) from completion of treatment. Sixty-one EBRT-alone patients experienced biochemical failure at a median interval of 1.4 years (range, 0.1 to 5.8 years).
Table 3 presents the 5-year actuarial rates of biochemical control for each treatment group separated by multiple characteristics. A higher Gleason score, higher clinical T stage, higher PSA nadir, shorter time interval from RT to nadir, malignancy in more than 50% of biopsy cores, and BED1.5 less than 85.0 Gy were significantly associated with biochemical failure on univariate analysis. On multivariate analysis of pretreatment factors, a higher pretreatment PSA, higher Gleason score, higher T stage, and EBRT alone were significantly associated with biochemical failure (Table 4). Although total dose did not demonstrate an association with biochemical failure, BED (as a continuous variable) did demonstrate a significant association on univariate analysis, whether using an alpha/beta of 1.5 Gy42 (P < .001) or an alpha/beta of 5.0 Gy (P < .001). A lower BED was also significantly associated with biochemical failure on multivariate analysis (P < .001) when BED was substituted for treatment modality.
Clinical Outcome In the EBRT + HDR group, 19 patients (12%) experienced clinical failure at a median interval of 1.6 years (range, 0.2 to 4.6 years) after completing RT. Twenty-five EBRT-alone patients (16%) experienced clinical failure at a median interval of 1.6 years (range, 0.1 to 5.8 years). The 5-year actuarial rates of clinical failure for EBRT + HDR and EBRT alone were 22% and 24%, respectively (P = .59; Table 2). On univariate analysis, a higher Gleason score, higher T stage, higher percentage of positive biopsy cores, perineural invasion, higher PSA nadir, and shorter time to nadir were significantly associated with clinical failure (Table 5). BED1.5 demonstrated borderline association (P = .09). On multivariate analysis of pretreatment factors, Gleason score and clinical T stage remained significant (Table 6).
Cause-Specific Survival The 5-year actuarial cause-specific survival rates were 95% and 92% for EBRT + HDR and EBRT alone, respectively (P = .33; Table 2). Cause-specific survival of various subgroups is listed in Table 7. On univariate analysis, a higher Gleason score, higher T stage, higher PSA nadir, and shorter time to nadir were associated with cause-specific survival. Only a higher Gleason score (P = .001) and T stage (P = .04) remained significant on multivariate analysis of pretreatment factors. The 5-year cause-specific survival rate for patients who experienced biochemical failure was 84% versus 100% for patients who did not experience biochemical failure (P < .001; Fig 2).
Complications For patients treated with EBRT + HDR, eight patients (5%) experienced Radiation Therapy Oncology Group grade 3 acute toxicity. No patient experienced grade 4 or 5 acute toxicity. Seven patients (4%) developed grade 3 late complications at a median interval of 2.4 years (range, 0.6 to 3.8 years). Grade 3 late toxicity consisted of urethral stricture in six patients (requiring dilation) and urinary incontinence in one patient after transurethral resection of the prostate performed 3.8 years after RT. No patient developed late grade 3 gastrointestinal morbidity. There have been no late grade 4 or 5 complications. The 5-year actuarial rate of grade 3 late complications was 9%. Forty-seven patients (29%) developed impotence at a median interval of 0.9 years (range, 0 to 6.0 years) after treatment.
In the current study, we performed a matched-pair analysis to compare our institution’s experience treating locally advanced prostate cancer with EBRT in combination with interstitial conformal HDR brachytherapy boosts to conventional EBRT alone. For 322 patients matched according to pretreatment PSA, Gleason score, clinical T stage, and PSA follow-up, the 5-year biochemical control rate for EBRT + HDR was significantly higher than for EBRT alone (67% v 44%; P < .001). Patients with similar pretreatment prognostic factors demonstrated significantly lower PSA nadir values (0.4 v 1.1 ng/mL) and achieved nadir at a longer time interval after RT (1.5 v 1.0 years) when treated with EBRT + HDR. Although EBRT + HDR has not yet demonstrated significantly improved clinical failure and cause-specific survival rates, patients from both treatment groups who failed biochemically were more likely to die as a result of prostate cancer. In addition, a shorter time to nadir demonstrated the closest correlation with cause-specific death of any factor analyzed (on univariate and multivariate analysis.) These findings indicate that EBRT + HDR may be superior to conventional EBRT alone for the treatment of locally advanced prostate cancer.
Several institutions have published encouraging results using EBRT in combination with a brachytherapy boost for locally advanced prostate cancer (Table 8). Table 9 also lists selected series using other treatment techniques for locally advanced prostate cancer. Five-year biochemical control rates vary markedly between series and decrease considerably for patients with pretreatment PSA levels
Similar to other dose-escalation studies, during the formative years of our study, implant doses were limited to establish feasibility and assess toxicity. These patients who received lower doses (5.50 to 6.50 Gy x 3, BED1.5 of 78.6 to 90.2 Gy) comprise the vast majority of patients who have been receiving follow-up for 5 years or more, indicating the potential for even greater improvement in treatment outcome with further dose escalation. Indeed, those 43 EBRT + HDR patients who received a BED1.5 of less than 85.0 Gy demonstrated a lower 5-year biochemical control rate (52%) and higher 5-year clinical failure rate (29%) than the 118 EBRT + HDR patients who received 85.0 Gy (88% biochemical control and 9% clinical failure; Tables 3 and 5). HDR brachytherapy offers some enticing radiobiologic and technical advantages. Several recent studies have indicated an alpha/beta ratio of 1.2 to 3.5 Gy in cases of prostate cancer for which hypofractionated HDR brachytherapy would seem ideal.42,47-49 In our dose-escalation series, HDR implants allowed a median BED (equivalent in 2.0-Gy fractions) of 92.0 Gy (range, 73.6 to 118.0 Gy), when applying an alpha/beta ratio of 1.5 Gy.42 Since February 1998, we have been delivering 10.5 Gy x 2 via HDR brachytherapy in combination with 46.0 Gy of EBRT to the pelvis for a BED1.5 of 118.0 Gy. Even with the relatively low statistical power of our series, BED demonstrated significant association with biochemical control as a continuous variable on univariate analysis, whether using an alpha/beta ratio of 1.5 Gy or an alpha/beta ratio of 5.0 Gy. In addition, BED was significant on multivariate analysis including all pretreatment factors. A second advantage of HDR brachytherapy is the use of intraoperative real-time dosimetric calculation, eliminating the effect of organ motion and daily setup variation encountered with EBRT and postimplant edema encountered with permanent seed brachytherapy. Also, the median rectal dose of 63% (calculated at the anterior edge of the TRUS probe in the reference plane) for the 161 EBRT + HDR patients included in this analysis can only be achieved with the rapid dose gradient of brachytherapy. When using HDR, geometric optimization also alleviates the dose heterogeneity and operator dependency encountered with permanent seed placement. The online interactive software further reduces operator dependency and enhances conformality by determining desired needle positions. In light of all of these potential advantages, conformal HDR brachytherapy may provide the optimal mechanism for delivery of a high radiobiologically effective dose to the prostate while avoiding normal tissue toxicity. Because longer follow-up is required for accurate clinical failure and survival analyses, we have focused primarily on early end points such as PSA nadir, time to nadir, and biochemical control. Also, due to the long natural history of prostate cancer and the significant comorbidities of many elderly patients, survival comparisons in nonrandomized studies may be rendered suspect. To provide clinicians with an early surrogate of treatment efficacy, a standard definition of biochemical control after RT has been adopted.27 Several recent studies have demonstrated a statistically significant association of biochemical control with clinical recurrence and cause-specific survival (including this analysis).23-26 In addition, multiple studies indicate that a lower PSA nadir and shorter time to nadir are associated with biochemical and clinical failure.25,27,37,50-59 In fact, some previous analyses indicate that time to PSA nadir may demonstrate a stronger correlation with clinical outcome than any other pretreatment or treatment-related factor.37,38 On the basis of these early end points, EBRT and conformal HDR brachytherapy is clearly superior to EBRT alone in this data set.
There are some potential criticisms of our current analysis. First, the EBRT-alone patients received a median dose of only 66.6 Gy, which is modest when compared with current standards. Multiple recent studies have indicated a dose-response relationship for prostate cancer treated with conformal EBRT,2-7,60-62 high-energy neutrons,8,63,64 hyperfractionated RT,65 particle-beam therapy,66,67 and interstitial implants.51,68,69 Second, the EBRT + HDR group received whole-pelvic RT, whereas the EBRT-alone group was treated to the prostate alone. Although the majority of studies have not demonstrated improved outcome with treating the whole pelvis,70-79 some studies have indicated a potential benefit in certain subgroups with high-risk prostate cancer.80-86 Third, none of these patients received hormonal therapy. Although this simplifies analysis in some respects, two randomized trials have indicated a 5-year overall survival advantage with the addition of goserelin to EBRT for clinical stage T3/T4 or high-grade prostate cancer.9,11 Although the EORTC study demonstrated high 5-year biochemical control rates similar to our study (Table 9), the patients received treatment for the majority of the 5-year period.9,87 Finally, although a matched-pair analysis stratifies patients according to the primary prognostic variables by including them as matching criteria (ie, PSA, Gleason score, T stage, and follow-up), there may be selection bias in lesser prognostic factors between the two treatment groups. Although age has demonstrated no association with biochemical failure in several studies,38,50,88,89 younger age has been associated with a higher rate of clinical failure in some reports.24,90-93 A recent analysis of 1,094 patients treated with EBRT alone at our institution indicated that younger age was associated with clinical failure on both univariate and multivariate analyses.25 The 8-year actuarial rate of distant metastasis increased from 14% for patients Whereas treatment outcome seems encouraging thus far, acute and chronic toxicity has also remained quite low. Patients who received two implants have yet to experience a grade 3/4 late complication. However, longer follow-up and further dose escalation are needed to shed more light on the impact of an HDR brachytherapy boost. In the future, we plan to compare EBRT + HDR with more modern EBRT-alone techniques currently performed at our institution, including adaptive RT (accounting for organ motion and daily setup variation) and dose-escalating intensity-modulated RT.96-98 Although the optimal treatment for locally advanced prostate cancer remains unresolved, techniques using conformal HDR brachytherapy continue to provide encouraging results. In conclusion, locally advanced prostate cancer patients treated with EBRT in combination with conformal HDR brachytherapy demonstrate lower PSA nadir levels, longer time intervals to PSA nadir, and improved biochemical control compared with treatment with conventional doses of EBRT alone. Although a difference in cause-specific survival was not demonstrated at 6 years between the two treatment groups, patients in both treatment groups who experienced biochemical failure had significantly lower cause-specific survival rates than biochemically controlled patients. These findings indicate that EBRT + HDR may be superior to conventional EBRT alone in the treatment of patients with locally advanced prostate cancer.
We thank Chris Mitchell, RN, Michelle Wallace, RN, OCN, and Maria Hardy, MSN, for their assistance in data management and Mamtha Balasubramaniam, MS, for her assistance with statistical analysis.
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Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
3.9, 4.0 to 9.9, 10.0 to 19.9, or 
