Multisector prostate dosimetric quality: analysis of a large community database.

PURPOSE: To evaluate multi-institutional prostate brachytherapy dosimetric quality using multisector analysis. METHODS AND MATERIALS: In the database, 4547 patients underwent brachytherapy (3094 for (125)I, 1437 for (103)Pd, and 16 for (131)Cs). The original prostate postimplant dosimetry was reported using the maximum dose covering 90% of the prostate volume (D90) and the percentage of the prostate volume covered by the prescription dose (V100). Retrospectively, the dosimetry of all implants was recalculated after segmenting the prostate into 12 sectors (anterior, left and right lateral and posterior, about the center of gravity, and subdivided lengthwise into three-base, midgland, and apex). The dosimetric quality of each sector and combinations of sectors was compared across radionuclides. RESULTS: For each radionuclide, there was no significant difference between monotherapy and boost in terms of V100 or D90. When classified as excellent (V100 ≥ 90%), standard (V100 ≥ 80%), or minimal (V100 < 80%), 33.0%, 4.6%, and 10.5% of all base, midgland, and apical sectors, respectively, were of minimal quality. Specifically, 59.2% of the anterior base and 30.3% of the posterior base sectors were minimal. At the anterior midgland and apex, 22% and 19% of sectors were minimal. Excellent quality was observed in more than 90% of lateral and posterior midgland sectors and in >70% of lateral and posterior sectors. When stratified by (103)Pd vs. (125)I, sector analysis did not result in clinically significant dosimetric differences. CONCLUSIONS: Coverage of base sectors was inferior to midgland and apical sectors, and coverage of anterior sectors was notably inferior to lateral and posterior sectors. Further critique of brachytherapy planning and intraoperative technique is necessary for brachytherapists to minimize these dosimetric differences.

Permanent prostate brachytherapy extracapsular radiation dose distributions: analysis of a multi-institutional database.

PURPOSE: Periprostatic brachytherapy doses impact biochemical control. In this study, we evaluate extracapsular volumetric dosimetry following permanent prostate brachytherapy in patients entered in a multi-institutional community database. MATERIAL AND METHODS: In the database, 4547 patients underwent brachytherapy (3094 - (125)I, 1437 - (103)Pd and 16 - (131)Cs). Using the originally determined prostate volume, a 5 mm, 3-dimensional peri-prostatic anulus was constructed around the prostate (except for a 2 mm posterior margin), and evaluated in its entirety and in 90° segments. Prostate dosimetric parameters consisted of a V100 and D90 while the annular dosimetry was reported as a V100. RESULTS: The intraprostatic V100 and D90 for (103)Pd, and (125)I were statistically comparable when stratified by isotope and/or monotherapy vs. boost. The overall mean V100 for the periprostatic annulus was 62.8%. The mean V100 at the base (51.6%) was substantially less than the apex (73.5%) and midgland (65.9%). In addition, for all patients, the anterior V100 (45.7%) was less than the lateral (68.8%) and the posterior (75.0%). The geometric V100 annular differences were consistent when evaluated by isotope. Overall, the V100 was higher in the (125)I cohort. CONCLUSIONS: The optimal extracapsular brachytherapy dose and radial extent remains unknown, but will prove increasingly important with reductions and/or elimination of supplemental external beam radiation therapy. The large multi-institutional community database demonstrates periprostatic annular doses that are not as robust as those in selected high volume brachytherapy centers, and may be inadequate for optimal biochemical control following monotherapeutic brachytherapy, especially in higher risk patients.

Impact of small prostate size on postimplant prostate dosimetry: analysis of a large community database.

PURPOSE: Achieving high-quality permanent interstitial brachytherapy in smaller prostates is thought to be more difficult than in larger glands. This study evaluates 4547 implants in a large community database to test this hypothesis. METHODS AND MATERIALS: From January 2003 to October 2010, 4547 prostate brachytherapy implants from a large community database were analyzed. The cohort was divided into three groups based on size, namely smaller (<30cm(3), n=1301), medium (30-40cm(3), n=1861), and large (>40cm(3), n=1385). Postimplant dosimetry, including D90, V100, and V100 by prostate sector, was performed for each implant. Comparison of mean V100 among small, medium, and larger prostate volume cohorts was performed using a one-way analysis of variance test. RESULTS: For the overall cohort, the D90 was 105% and 104% for monotherapy and boost, respectively. Mean D90 for small prostates was 106% and 104% for monotherapy and boost, respectively. Mean V100 for small prostates was 91.1% and 90.0%, respectively. Coverage for small prostates was as good or slightly better than larger glands. V100 by prostate sector revealed that there were no sectors for which smaller glands had significantly inferior coverage compared with larger glands. CONCLUSION: Although smaller prostates may in some respects be more technically difficult to implant than larger glands, a review of community-based brachytherapists reveals that with current implant techniques, good quality implants are readily achievable in men with smaller glands.

Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy.

PURPOSE: Recent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT. METHODS AND MATERIALS: Between April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. RESULTS: At 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p=0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p=0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p=0.14). CONCLUSIONS: Men with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason pattern 5.

Prognostic importance of tobacco use in men receiving definitive prostate brachytherapy.

PURPOSE: Several prominent publications have identified an overall association between tobacco use and an increased risk of disease recurrence and disease-specific mortality in prostate cancer patients. The authors explored whether tobacco use adversely impacts treatment outcomes in men treated with permanent interstitial brachytherapy. METHODS AND MATERIALS: From April 1995 to August 2008, 2057 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.5 years. The role of tobacco use as a prognostic factor for biochemical progression-free survival, cause-specific survival, and overall survival was investigated. Differences in survival between smokers and nonsmokers were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Current smokers presented with a lower body mass index (p<0.001), smaller prostate size (p=0.003), younger age (p<0.001), higher prostate-specific antigen level (p=0.002), a trend toward higher percentage biopsy core involvement (p=0.08), higher incidence of perineural invasion (p=0.015), and higher risk disease (p<0.001) than former or nonsmokers. There was no difference in biochemical progression-free survival (p=0.30) or cause-specific survival (p=0.72) at 10 years for smokers compared with nonsmokers. On univariate and multivariate analysis, tobacco use was an adverse risk factor for overall survival (p<0.001). There was no association between smoking and any prostate cancer-specific outcome. CONCLUSIONS: Smokers treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men who are nonsmokers.

Serum testosterone kinetics after brachytherapy for clinically localized prostate cancer.

PURPOSE: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. METHODS AND MATERIALS: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. RESULTS: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase ≥ 25%, 23% of men experienced a decrease ≥ 25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). CONCLUSION: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response does not seem related to temporal testosterone changes.

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy.

OBJECTIVE: To evaluate the relationship between pre-treatment erectile function and all-cause mortality in patients with prostate cancer treated with brachytherapy. PATIENTS AND METHODS: In all, 1279 consecutive patients with clinically localized prostate cancer and pre-implant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) underwent brachytherapy. Potency was defined as an IIEF-6 score of ≥13 without pharmacological or mechanical support. Patients were stratified into IIEF-6-score cohorts (≤12, 13-23 and 24-30). The median follow-up was 5.0 years. RESULTS: The 8-year overall survival (OS) of the study population was 85.1%. The 8-year OS for IIEF-6scores ≤12, 13-23 and 24-30 were 78.0%, 92.8% and 91.4%, respectively (P < 0.001). Cardiovascular events accounted for a significant portion of deaths in each IIEF-6 group. When combined with other risk factors for cardiovascular disease, an IIEF-6 score of ≤12 had an additive effect on all-cause mortality (IIEF-6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%). CONCLUSIONS: A pre-implant IIEF-6score of ≤12 was associated with a higher incidence of all-cause mortality. Pre-treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients. Aggressive treatment of medical co-morbidity is warranted to impactOS.

The impact of diabetes mellitus on survival in men with clinically localized prostate cancer treated with permanent interstitial brachytherapy.

PURPOSE: Patients with cancer of any origin with preexisting diabetes mellitus (DM) are at increased risk for all-cause mortality compared with those without DM. However, the influence of DM on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) has not been clearly defined for men with clinically localized prostate cancer treated with brachytherapy. MATERIALS AND METHODS: From April 1995 to May 2006, 1624 consecutive patients underwent brachytherapy with or without supplemental therapies. A prebrachytherapy diagnosis of diabetes was present in 199 patients (12.3%). Median follow-up was 7.8 years. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate-resistant disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. RESULTS: In patients without (n=1425) and with (n=199) DM, CSS was 97.2% versus 100% (P=0.168), bPFS was 95.6% versus 95.7% (P=0.960), and OS was 77.3% versus 56.0% at 12 years (P=0.003). In Cox regression analysis, OS in nondiabetic patients was most closely related to patient age, coronary artery disease, tobacco consumption, and androgen deprivation. In patients with diabetes, OS was related to patient age and coronary artery disease. In patients without diabetes, CSS was associated with Gleason score and clinical stage. No patient with diabetes died of prostate cancer. Patients with DM were more likely to die of cardiovascular disease (17.8% vs. 12.4%, P=0.007). CONCLUSIONS: DM does not impact CSS or bPFS after brachytherapy. OS is significantly lower in patients with diabetes due to more deaths from cardiovascular disease.

The effect of pro-qura case volume on post-implant prostate dosimetry.

PURPOSE: To evaluate the effect of prostate brachytherapy case volume on postimplant dosimetric quality in Pro-Qura proctored programs. METHODS AND MATERIALS: From August 1999 to December 2008, the computed tomography datasets for 6,600 prostate implants performed by 129 brachytherapists were submitted to Pro-Qura for dosimetric analysis. Brachytherapists were divided into three roughly equal-sized terciles based on total case volume. Postimplant computed tomography scans were obtained at a median of 30 days. Excellent target coverage was defined by a V100≥90% and D90≥100% minimum prescribed peripheral dose. To determine if the number of excellent implants improved with increasing case numbers, each brachytherapist's series of implants was bisected into early and late experience by a moveable critical point. RESULTS: For the entire cohort, the mean V100 and D90 were 89.2% and 102.8%, respectively, with 47.7% of the implants scored as excellent. Brachytherapists in the highest-case tercile had a significantly greater fraction of excellent target coverage (57.9%) than did those in the two lower terciles (39.5% and 45.7%, p=0.015). Twenty-one (25.6%) of the 82 brachytherapists with sufficient case volume for dosimetric improvement analyses demonstrated quality improvement over time. Although there was no significant difference between prostate volume and seed strength, the number of seeds used was significantly greater in adequate implants. CONCLUSIONS: The highest-volume brachytherapists were most likely to obtain excellent target coverage. We are encouraged that in general practice, nearly 48% of all implants were scored excellent. It is conceivable that with greater expert third-party involvement, an even greater percentage of cases with excellent target coverage will become reality.

Relationship between prostate cancer mortality and number of unfavourable risk factors in men treated with definitive brachytherapy.

OBJECTIVE: To explore whether the number of unfavourable pretreatment risk factors predicts cause-specific mortality in men treated with prostate brachytherapy. PATIENTS AND METHODS: Between April 1995 and March 2006, 739 patients were treated who had at least one of the following adverse risk factors: pretreatment prostate-specific antigen (PSA) level of >10 ng/mL, a Gleason score of > or =7, clinical stage > or =T2b, or a PSA velocity (PSAV) of >2 ng/mL/year. Supplemental external beam radiotherapy (EBRT) was delivered to 464 (62.8%) men and 301 (40.7%) received androgen deprivation therapy (ADT). Of men with more than two risk factors, 87% received EBRT and 62% received ADT. RESULTS: The biochemical progression-free survival (bPFS), cause-specific survival (CSS) and overall survival for all patients were 95.0%, 97.9% and 70.0% at 12 years. Men with three or four risk factors had a prostate cancer-specific mortality (PCSM) at 12 years of 5.3%, vs 1.7% for men with one or two risk factors (P= 0.006). When 'percentage of positive biopsy cores >50%' replaced PSAV as a risk factor, men with two or more risk factors had a PCSM of 8.9%, vs 1.0% for men with one or two risk factors (P= 0.001). There was no difference in all-cause mortality between the groups in either analysis. CONCLUSION: Multimodal brachytherapy results in high rates of bPFS and CSS, even for men with several unfavourable risk factors. Men with two or more unfavourable risk factors had a slightly greater risk of PCSM and no difference in all-cause mortality. The presence of three or four unfavourable intermediate-risk factors does not appear to clearly identify a group that requires further treatment intensification, although the percentage of positive cores might be more predictive than PSAV.

Erectile function durability following permanent prostate brachytherapy.

PURPOSE: To evaluate long-term changes in erectile function following prostate brachytherapy. METHODS AND MATERIALS: This study included 226 patients with prostate cancer and preimplant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) who underwent brachytherapy in two prospective randomized trials between February 2001 and January 2003. Median follow-up was 6.4 years. Pre- and postbrachytherapy potency was defined as IIEF-6 > or = 13 without pharmacologic or mechanical support. The relationship among clinical, treatment, and dosimetric parameters and erectile function was examined. RESULTS: The 7-year actuarial rate of potency preservation was 55.6% with median postimplant IIEF of 22 in potent patients. Potent patients were statistically younger (p = 0.014), had a higher preimplant IIEF (p < 0.001), were less likely to be diabetic (p = 0.002), and were more likely to report nocturnal erections (p = 0.008). Potency preservation in men with baseline IIEF scores of 29-30, 24-28, 18-23, and 13-17 were 75.5% vs. 73.6%, 51.7% vs. 44.8%, 48.0% vs. 40.0%, and 23.5% vs. 23.5% in 2004 vs. 2008. In multivariate Cox regression analysis, preimplant IIEF, hypertension, diabetes, prostate size, and brachytherapy dose to proximal penis strongly predicted for potency preservation. Impact of proximal penile dose was most pronounced for men with IIEF of 18-23 and aged 60-69. A significant minority of men who developed postimplant impotence ultimately regained erectile function. CONCLUSION: Potency preservation and median IIEF scores following brachytherapy are durable. Thoughtful dose sparing of proximal penile structures and early penile rehabilitation may further improve these results.

Pretreatment serum testosterone and androgen deprivation: effect on disease recurrence and overall survival in prostate cancer patients treated with brachytherapy.

PURPOSE: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. METHODS AND MATERIALS: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined for each deceased patient. RESULTS: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). CONCLUSIONS: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.

Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange.

BACKGROUND: In this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy. METHODS AND MATERIAL: From May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen (PSA)< or =0.40ng/mL after nadir. Patients with metastatic prostate cancer or hormone refractory disease without obvious metastases who died of any cause were classified as died of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple parameters were evaluated for impact on survival. RESULTS: At 9 years, Agent Orange-exposed men were least likely to remain biochemically controlled (89.5%, 100%, and 97.2% in Agent Orange-exposed, nonexposed veterans, and nonveterans, respectively, p=0.012). No significant differences in cause-specific (CSS) (p=0.832) or overall survival (OS) (p=0.363) were discerned. In multivariate analysis, CSS was best predicted by Gleason Score and day 0 D(90), whereas Gleason Score, % positive biopsies, and D(90) predicted for bPFS. None of the evaluated parameters predicted for OS, however, a trend was identified for better OS in younger patients and those with a higher D(90). In addition, Agent Orange exposure did not predict for any of the survival parameters. To date, 22 patients have died (metastatic prostate cancer two, second malignancies nine, cardiovascular disease eight, trauma two, and pulmonary one). CONCLUSIONS: In this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis.

Biochemical and functional outcomes following brachytherapy with or without supplemental therapies in men < or = 50 years of age with clinically organ-confined prostate cancer.

OBJECTIVES: Despite favorable long-term prostate brachytherapy outcomes, there remains a bias to recommend radical prostatectomy for young patients. Herein, we report cause-specific survival, biochemical progression-free survival (bPFS), overall survival and functional outcomes in men < or =50 years of age who underwent brachytherapy with or without supplemental therapies. METHODS: From October 1995 to November 2004, 42 consecutive patients < or =50 years of age underwent permanent interstitial brachytherapy. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The mean and median follow-up was 5.6 and 5.1 year. bPFS was defined as a prostate-specific antigen < or =0.40 ng/mL after nadir. Functional outcome determinations included urinary, bowel and erectile function evaluations. Multiple clinical, treatment and dosimetric parameters were evaluated for impact on survival. RESULTS: Cause-specific survival, bPFS, and overall survival for the entire cohort were 100%, 97.7%, and 100%, respectively. To date, only one patient has failed biochemically. Median time to International Prostate Symptom Score resolution was 3 months. No patient required a postimplant transurethral resection of the prostate or developed urinary incontinence. Two patients developed bulbomembtranous urethral strictures. The overall potency preservation rate was 75.6% (International Index of Erectile Function-6 >13 without mechanical or pharmacologic support). Bowel habits were reported to be the same or better than prior to treatment in 92.5% patients. No severe rectal complications requiring therapeutic intervention occurred. CONCLUSIONS: Men < or =50 years of age have favorable biochemical and functional outcomes following brachytherapy. Depending on risk group assignment, brachytherapy with or without supplemental therapies should be considered a viable option for all healthy men regardless of age.

The impact of acute urinary morbidity on late urinary function after permanent prostate brachytherapy.

PURPOSE: Acute prostate brachytherapy-related morbidity is dominated by urinary symptomatology. In this study, we evaluated the effect of severe early brachytherapy-related urinary morbidity on late urinary function. METHODS AND MATERIALS: From January 1998 to September 2003, 1029 patients were implanted for clinical stage T1b-T3a (2002 American Joint Committee on Cancer [AJCC] criteria) prostate cancer. Five hundred sixteen (50.1%) received supplemental external beam radiation therapy and 440 (42.8%) received androgen deprivation therapy. Severe acute urinary morbidity (SAUM) was defined as a dysuria frequency score of at least 4 (of 5), a dysuria severity score of at least 8 (of 10), an internation prostate symptom score (IPSS) elevated to at least 30 or 15 above preimplant value for 4 weeks, and/or requirement of a urinary catheter for at least 5 days. Dysuria severity and frequency resolution were defined as a return to within one point of baseline. IPSS resolution was defined as a return to within two points of baseline. RESULTS: Of the 1029 patients, 175 met at least one of the criteria for inclusion. Dysuria frequency resolved in 5.0 vs. 1.3 weeks and dysuria severity in 5.7 vs. 1.4 weeks, for patients with and without SAUM. The mean time for IPSS resolution was 13.8 vs. 6.6 weeks, for patients with and without SAUM. The incidence of transurethral resection (2.3% [4/173] vs. 1.5% [13/841]) and bulbomembranous urethral strictures (2.2% [4/175] vs. 1.8% [15/854]) were comparable among patients with and without SAUM. CONCLUSIONS: Patients experiencing brachytherapy-related SAUM have long-term urinary function and complications comparable to patients who did not develop SAUM.

Variability of prostate brachytherapy pre-implant dosimetry: a multi-institutional analysis.

PURPOSE: To conduct a multi-institutional comparison of prostate brachytherapy pre-implant dosimetry of Pd-103 and I-125. METHODS AND MATERIALS: Eight experienced brachytherapists submitted Pd-103 and I-125 monotherapeutic and boost pre-implant dosimetry plans for central review. All 32 plans were calculated using the same transrectal ultrasound volumetric study. Seeds of any strength were acceptable, but were restricted to Theraseed Model 200 (Theragenics Inc., Buford, GA) and Oncura Oncoseed Model 6711 (Oncura, Plymouth Meeting, PA). The dosimetric analysis included evaluation of target volume, target to prostate ratio, target length, number of needles, seed activity, number of seeds, total activity, total activity divided by treatment planning volume, the use of extracapsular seeds, and average treatment margins (defined as the perpendicular distance between the prostate capsule and the 100% isodose line). Prostate coverage was defined in terms of V(100)/V(150)/V(200)/V(300) and D(100)/D(90)/D(50), whereas urethral dosimetry consisted of UV(100)/UV(150)/UV(200) and UD(90)/UD(50). RESULTS: The mean planning target volume to prostate volume ratio varied dramatically (mean 1.29, range 0.99-1.76) with the target length ranging from 3.5 to 4.5 cm. Although the prostate V(100) was >95% in all cases, the V(150) ranged from 29.9% to 92.1% and the V(200) from 6.72% to 52.5%. The urethral V(100) was 100% in all cases with six of the eight brachytherapists limiting the UV(150) to <3%. However, the median urethral dose varied by up to 50%. Treatment margins also varied significantly (average 3.98 mm, range 0.32-7.68 mm). All brachytherapists used extracapsular seeds with five implanting >25% of the seeds in extracapsular locations (range 6.4-58.2%). In addition, significant variability existed in the number of needles, number of seeds, and seed strength. CONCLUSIONS: This study highlights the substantial variability that exists regarding target volume, seed strength, dose homogeneity, treatment margins, and extracapsular seed placement, although prostate brachytherapy prescription doses are uniform. The standardization of pre-implant dosimetry is essential for meaningful multi-institutional comparisons of biochemical outcomes and morbidity.

Erectile function after prostate brachytherapy.

PURPOSE: To evaluate erectile function after permanent prostate brachytherapy using a validated patient-administered questionnaire and to determine the effect of multiple clinical, treatment, and dosimetric parameters on penile erectile function. METHODS AND MATERIALS: A total of 226 patients with preimplant erectile function determined by the International Index of Erectile Function (IIEF) questionnaire underwent permanent prostate brachytherapy in two prospective randomized trials between February 2001 and January 2003 for clinical Stage T1c-T2c (2002 American Joint Committee on Cancer) prostate cancer. Of the 226 patients, 132 were potent before treatment and, of those, 128 (97%) completed and returned the IIEF questionnaire after brachytherapy. The median follow-up was 29.1 months. Potency was defined as an IIEF score of > or =13. The clinical, treatment, and dosimetric parameters evaluated included patient age; preimplant IIEF score; clinical T stage; pretreatment prostate-specific antigen level; Gleason score; elapsed time after implantation; preimplant nocturnal erections; body mass index; presence of hypertension or diabetes mellitus; tobacco consumption; the volume of the prostate gland receiving 100%, 150%, and 200% of the prescribed dose (V(100/150/200)); the dose delivered to 90% of the prostate gland (D(90)); androgen deprivation therapy; supplemental external beam radiotherapy (EBRT); isotope; prostate volume; planning volume; and radiation dose to the proximal penis. RESULTS: The 3-year actuarial rate of potency preservation was 50.5%. For patients who maintained adequate posttreatment erectile function, the preimplant IIEF score was 29, and in patients with brachytherapy-related ED, the preimplant IIEF score was 25. The median time to the onset of ED was 5.4 months. After brachytherapy, the median IIEF score was 20 in potent patients and 3 in impotent patients. On univariate analysis, the preimplant IIEF score, patient age, presence of nocturnal erections, and dose to the proximal penis predicted for postimplant erectile function. However, in multivariate analysis, only the preimplant IIEF score and the D(50) to the proximal crura were statistically significant predictors of brachytherapy-related erectile function. CONCLUSIONS: Using a patient-administered validated quality-of-life instrument, brachytherapy-induced ED occurred in 50% of patients at 3 years. On multivariate analysis, preimplant erectile function and the D(50) to the proximal crura were the best predictors of brachytherapy-related erectile function. Because the proximal penis is the most significant treatment-related predictor of brachytherapy-related ED, techniques to minimize the radiation dose to the proximal penis may result in improved rates of potency preservation.

The impact of radiation dose to the urethra on brachytherapy-related dysuria.

PURPOSE: To determine the effect of urethral dose on dysuria after permanent prostate brachytherapy. METHODS AND MATERIALS: One hundred eight patients without a preimplant history of a transurethral resection underwent brachytherapy on one of two prospective randomized trials for clinical T1c-T2c (2002 AJCC) prostate cancer. Urethral dose was stratified into cohorts of <150% and 150% minimum peripheral dose (mPD) respectively. No patient received prophylactic alpha blockers. The median follow-up was 27.4 months. Dysuria was defined as pain and/or burning on urination and was evaluated on a 0-10 scale. Normalization of dysuria was defined as a return to within 1 point of baseline. Dysuria surveys were obtained before brachytherapy and at 1, 3, 6, and 12 months after implantation. Clinical, treatment, and dosimetric parameters evaluated included urethral dose, age, preimplant International Prostate Symptom Score (I-PSS), ultrasound volume, hormonal status, supplemental XRT, isotope, V(100/200), D(90), the maximum post-implant I-PSS, and the time to I-PSS resolution. RESULTS: The incidence of dysuria peaked at 85% one month after brachytherapy with subsequent resolution over time. Radiation dose to the urethra (stratified into cohorts of <150%, and 150% mPD) was not a significant predictor of prevalence, severity, or resolution of dysuria. In a multivariate analysis, isotope predicted for dysuria normalization while preimplant I-PSS and D(90) predicted for maximum dysuria; however, the area under the ROC curve and the Pearson correlation coefficient revealed weak correlations. CONCLUSIONS: Dysuria is common after brachytherapy, but typically minimal in severity. Urethral doses did not predict for either dysuria severity or normalization. Although preimplant I-PSS was the strongest predictor of maximum dysuria and isotope the best predictor for dysuria normalization, robust predictors for brachytherapy-related dysuria were not identified.

Brachytherapy-related dysuria.

OBJECTIVE: To evaluate the incidence and temporal resolution of dysuria after permanent prostate brachytherapy, and to identify predictors of brachytherapy-related dysuria. PATIENTS AND METHODS: The study included 130 patients with no history of transurethral resection of the prostate before treatment, who had brachytherapy on one of two prospective randomized trials, with explicitly planned and executed urethral-sparing techniques (100-150% minimum peripheral dose) using either 103Pd or 125I for clinical T1c-T2c prostate cancer. The median follow-up was 22.6 months. An alpha-blocker was initiated either prophylactically 2 weeks before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to normal, or withheld until the onset of significant brachytherapy-related urinary morbidity. Dysuria was evaluated on a 0-10 scale, before brachytherapy and then at 1, 3, 6 and 12 months afterward, with a median of four dysuria questionnaires per patient. Clinical, treatment and dosimetric variables evaluated included alpha-blocker, age, IPSS before and the maximum after treatment, prostate volume on ultrasonography, hormonal status, supplemental radiotherapy, isotope, urethral dose, V(100/200), D90, and time to obtaining a normal IPSS. RESULTS: The maximum incidence of dysuria was 85% at 1 month after brachytherapy, with subsequent resolution over time. The use of prophylactic tamsulosin resulted in a statistically lower dysuria severity score (difference of 2.7 vs 4.2, P < 0.005) at 1 month, with no discernible differences at 3, 6, 12 and 18 months. Patients with dysuria had a statistically higher IPSS. The dysuria resolved faster in patients implanted with 103Pd but was unaffected by the use of supplemental radiotherapy and/or androgen deprivation therapy. In multivariate analysis, prophylactic alpha-blockers resulted in statistically lower maximum dysuria scores, while the maximum IPSS after implantation and isotope type (but only at 6 months) were the best predictors of the resolution of dysuria. CONCLUSIONS: Dysuria is common after brachytherapy but is typically mild. Prophylactic alpha-blockers gave significantly lower maximum dysuria scores but did not affect the time to the resolution of dysuria. The maximum IPSS after the implant was the best predictor of the resolution of dysuria.

Influence of body mass index on biochemical outcome after permanent prostate brachytherapy.

OBJECTIVES: To evaluate the impact of body mass index (BMI) on the 8-year biochemical outcome after permanent prostate brachytherapy with or without the addition of supplemental external beam radiotherapy and/or androgen deprivation therapy (ADT). METHODS: From April 1995 through February 2001, 686 consecutive patients underwent brachytherapy using either palladium-103 or iodine-125 for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) prostate cancer. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 59.5 months. The evaluated BMI subgroups were less than 25, 25.0 to 29.9, 30.0 to 34.9, and 35 or more kg/m2. Biochemical progression-free survival was defined by a prostate-specific antigen (PSA) level of 0.4 ng/mL or less after a nadir. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included BMI, patient age, clinical T stage, Gleason score, preimplant PSA level, risk group, percentage of positive biopsies, isotope, use of supplemental external beam radiotherapy, use of ADT, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose, minimal percentage of dose covering 90% of the target volume, tobacco use, and the presence of hypertension and diabetes. RESULTS: For the entire group, the actuarial 8-year biochemical progression-free survival rate was 95.8%, 95.6%, 94.1%, and 100% for patients in BMI categories less than 25, 25.0 to 29.9, 30.0 to 34.9, and 35 or more kg/m2, respectively. In hormone-naive and hormone-manipulated patients free of biochemical progression, the median post-treatment PSA level was less than 0.1 ng/mL. When integrated across risk groups and ADT use, BMI had no statistically significant impact on biochemical progression-free survival. At last follow-up, 5 patients (0.7%) had died of metastatic prostate cancer. In multivariate Cox regression analysis, pretreatment PSA level, Gleason score, clinical stage, percentage of positive biopsies, ADT use, and tobacco status, but not BMI, were statistically significant predictors of 8-year biochemical progression-free survival. CONCLUSIONS: Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low, intermediate, and high-risk patients. When integrated across risk groups and hormonal status, BMI had no statistically significant influence on biochemical progression-free survival.