3-D Conformal HDR Brachytherapy as Monotherapy for Localized Prostate Cancer

PURPOSE: Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning. PATIENTS AND METHODS: Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) < or = 10 ng/ml, Gleason score < or = 7 and clinical stage < or = T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT((R)) was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (D(ref)) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D(90), D(10) urethra, and D(10) rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales. RESULTS: Median D(90) was 106% of D(ref) (range: 93-115%), median D(10) urethra 159% of D(ref) (range: 127-192%), and median D(10) rectum 55% of D(ref) (range: 35-68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred. CONCLUSION: 3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.     

What is the optimal dose for 125I prostate implants? A dose-response analysis of biochemical control, posttreatment prostate biopsies, and long-term urinary symptoms

PURPOSE: To define the optimal dose for 125I prostate implants by correlating post implant CT dosimetry findings with urinary symptoms, biochemical failure, and posttreatment biopsies. METHODS AND MATERIALS: Patients with T1-T2, Gleason score 2-6 prostate cancer treated with I-125 brachytherapy were analyzed. Group 1 (276 patients) was observed from 18 to 108 months (median, 34 months) and had urinary symptoms prospectively assessed using the International Prostate Symptom Score (IPSS) system. Group 2 (181 patients) observed from 24 to 108 months (median, 44 months) and did not receive hormonal therapy. Implant dose was defined as the D90 (dose delivered to 90% of the prostate on a dose-volume histogram). Patients were analyzed by dose categories: <140 Gy, 140 to <160 Gy, 160 to <180 Gy, and > or =180 Gy. In Group 1, the mean pre- to postimplant IPSS scores were compared in different dose categories by using a matched paired t test. In Group 2, the effect of dose on biochemical control was tested with actuarial methods by using the American Society for Therapeutic Radiology and Oncology definition and on local control with posttreatment biopsies (113 patients). RESULTS: A comparison of pre- with postimplant IPSS revealed no significant changes in scores in the dose groups <180 Gy except for small changes in urgency and bladder emptying in the dose group <140 Gy. In dose group >180 Gy, mean scores changed from 0.5 to 1.0 (p=0.002) for emptying, 0.76 to 1.29 (p=0.004) for weak stream, 0.24 to 0.51 (p=0.009) for straining, 1.55 to 1.82 (p=0.05) for nocturia, and 6.3 to 8.45 (p=0.0009) for the total score. Freedom from biochemical failure (FFBF) at 5 years was 68% for doses <140 Gy, 97% for 140 to <160 Gy, 98% for 160 to <180 Gy, and 95% for > or =180 Gy (p=0.0025). Overall, patients with doses <140 Gy (median follow-up, 66 months) had an FFBF of 68%, compared with 96% for patients with doses > or =140 Gy (median follow-up, 35 months; p=0.0002). Multivariate analysis found dose to be the most significant factor affecting FFBF. Positive biopsies were found in 23% for doses <140 Gy, 21% for 140 to <160 Gy, 10% for 160 to <180 Gy, and 8% for > or =180 Gy. Overall, biopsies were positive in 22% for doses <160 Gy vs. 9% for > or =160 Gy (p=0.05). CONCLUSIONS: Optimal 125I prostate implants should deliver a D90 of 140-180 Gy, on the basis of postimplant dosimetry. Doses of <140 Gy are associated with increased biochemical failure, and doses >180 Gy with a small increase in long-term urinary symptoms.     

The nature and extent of urinary morbidity in relation to prostate brachytherapy urethral dosimetry

PURPOSE: This study investigates whether the location and dose of urethral radiation received during transperineal interstitial permanent prostate brachytherapy determine the degree and type of urinary symptoms experienced subsequently. METHODS AND MATERIALS: Data from a prospectively acquired database of 219 men treated with transperineal interstitial permanent prostate brachytherapy using (125)I (prescribed dose 145Gy) between May 2001 and June 2003 were reviewed. To assess the effect of regional urethral dosimetry, the prostate was divided into equal thirds (proximal, mid, and apical) with doses beyond this considered distal. Mean and peak doses for each region were correlated with total International Prostate Symptom Score (IPSS) and the irritative and obstructive components of the score. IPSS values at 1 month postimplant, time to resolution of IPSS, and the need for catheterization were used as outcome variables and analyzed with respect to dose using logistic and linear regression. RESULTS: Peak and average doses with standard deviations to the proximal urethra were 168 (24) and 147 (24)Gy, mid prostatic urethra 192 (24) and 181 (21)Gy, and apical urethra 201 (28) and 192 (26)Gy. Catheterization was required for 28 men and was predicted by larger pretreatment transrectal ultrasound (TRUS) volume (OR 1.06 per unit change; 95% CI 1.03-1.10; p<0.001) and lower UV(150) (OR 0.30; 95% CI 0.13-0.68; p=0.004) in multivariate analysis. Greater IPSS at baseline (p<0.001) and preoperative TRUS volume (p=0.012) but conversely smaller D(30) doses (p=0.003) were predictive of IPSS outcomes at 1 month. IPSS returned to within two points of baseline for 72.2% of men by 1 year and 83.3% by 24 months. This was predicted by higher IPSS at baseline (OR 6.0; 95% CI 2.72-13.22; p<0.001), higher D(30) (OR 1.17; 95% CI 1.01-1.36; p=0.031), and lower V(100) (OR 0.39; 95% CI 0.22-0.70; p=0.002). Prostatic urethral segmental dosimetry failed to predict the need for catheterization, the nature of the urinary symptoms, or their time to resolution. CONCLUSIONS: Previously identified factors of importance for urinary morbidity such as pretreatment prostate volume and baseline urinary function were reemphasized in this study. Regional urethral dosimetry within contemporary practice does not seem to influence the nature or extent of urinary symptoms after prostate brachytherapy. Consequently, region sparing dosimetric modifications are not warranted to alter symptomatic outcomes.     

The effects of edema on urethral dose following palladium-103 prostate brachytherapy.

The effects of edema on urethral dose after interstitial prostate brachytherapy with palladium-103 (103Pd) were studied. Fifty patients underwent a 90-Gy 103Pd implant followed by dosimetric computed tomography (CT). Twenty-one days later, a Foley catheter was reinserted and a dosimetric CT was repeated. The mean reduction in prostate volume between day 0 and day 21 was 16%. Median prostate D90 on day 0 was 89.7 Gy (range 59.5 to 127) and 99.5 Gy (range 62.5 to 130) on day 21. Median prostate V100 was 90% (range 63 to 98%) on day 0 and 96% (range 66 to 99%) on day 21. Median V150 was 61% (range 31 to 85%) on day 0 and 75% (range 39 to 93%) on day 21. Median urethral D50 was 107 Gy (range 57 to 201) on day 0 and 126 Gy (range 64 to 193) on day 21. Regression analysis demonstrated a significant correlation between the decrease in the prostate volume and the increased urethral D50 (r 0.58, p < 0.05). Acute urinary toxicity was 32% grade 0, 38% grade 1, and 30% grade 2. The median urethral D50 increased by a mean of 18% with a correlation coefficient of 0.58 (p < 0.05). Catheterization of the urethra was well tolerated and was of value in better characterizing urethral dose after 103Pd brachytherapy.     

Relationship of the International Prostate Symptom score with urinary flow studies, and catheterization rates following 125I prostate brachytherapy

PURPOSE: Prostate cancer patients undergoing 125I brachytherapy were reviewed. A relationship between pretreatment risk factors including International Prostate Symptom (IPS) score, urinary flow studies, and posttreatment urinary morbidity was assessed. METHODS AND MATERIALS: Pretreatment IPS scores and urinary flow studies on 207 patients were reviewed. Relationship between scores and acute urinary morbidity was evaluated. RESULTS: Median age, 64 years; median baseline IPS score, 9; median prostate volume, 36 cc. Catheterization was required in 18% of patients. Baseline IPS score and peak flow rate (PFR) varied inversely, demonstrating that PFR for patients requiring a catheter was lower than that for those not requiring catheterization. Univariate regression showed that prostate volume, prior hormone therapy, and PFR were statistically predictive of postimplant urinary retention. For every one-unit increase in PFR, the odds of catheterization decreased by 6%. Multivariate analysis demonstrated that only PFR and prostate volume were predictive of postimplant urinary retention. CONCLUSIONS: Pretreatment IPS questionnaire and urinary flow studies assist in predicting risk of urinary morbidity and retention post-125I brachytherapy for prostate cancer.     

Health-Related Quality of Life after Permanent Interstitial Brachytherapy for Prostate Cancer

PURPOSE: To determine dosimetric risk factors for increased toxicity after permanent interstitial brachytherapy for prostate cancer. PATIENTS AND METHODS: Quality of life questionnaires (Expanded Prostate Cancer Index Composite) of 60 and 56 patients were analyzed after a median posttreatment time of 6 weeks (A-acute) and 16 months (L-late). The corresponding CT scans were performed 30 days after the implant. The prostate, rectal wall, and base of seminal vesicles were contoured. Prostate volume, number of seeds and needles as well as dosimetric parameters were correlated with the morbidity scores. RESULTS: For a prostate volume of 38 +/- 12 cm(3) (mean +/- standard deviation), 54 +/- 7 (125)I sources (Rapid Strands), activity of 22.6 +/- 3.0 MBq [0.61 +/- 0.08 mCi]) were implanted using 20 +/- 6 needles. Improved late urinary function scores resulted from a higher number of sources per cm(3) (> or = 1.35). A prostate D(90) < 170 Gy (A)/< 185 Gy (L) and base of seminal vesicle D(10) < 190 Gy (A and L) were associated with higher urinary function scores. Late rectal function scores were significantly higher for patients with a prostate V(200) < 50% and V(150) < 75%. Patients with a prostate volume < 40 cm(3) reached better sexual function scores (A and L). A higher number of needles per cm(3) (> or = 0.5) resulted in improved late urinary, bowel and sexual function scores. CONCLUSION: Quality of life after a permanent implant can be improved by using an adequate amount of sources and needles. With an increasing number of seeds per cm(3), dose homogeneity is improving. A prostate D(90) < 170 Gy and a base of seminal vesicle D(10) < 190 Gy (as an indicator of the dose to the bladder neck and urethral sphincter) can be recommended to maintain a satisfactory urinary function.     

3D interstitial HDR brachytherapy combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Preliminary results.

BACKGROUND: Evaluation of feasibility, tolerance and efficiency for a new 3D interstitial HDR brachytherapy technique combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. PATIENTS AND METHODS: Between January 1997 and August 1998 we treated 35 patients with stage cT1-3 N0 M0 prostate cancer. Thirty-two patients with a follow-up of 12 to 28 months (median: 18 months) were evaluated. After ultrasound-guided transrectal implantation of 4 non-parallel needles, CT based 3D brachytherapy treatment planning ("Offenbach system") was performed. All patients received 4 fractions brachytherapy using a fractional dose of 5 or 7 Gy. Time between each fraction was 14 days. After brachytherapy 3D external irradiation followed up to 39.6 or 45.0 Gy. All patients received androgen deprivation, starting 2 to 19 months before brachytherapy, ending 3 months after 3D external radiotherapy. RESULTS: Posttreatment PSA levels dropped to < 1.5 ng/ml in 29/32 patients (91%). In 25 patients PSA levels were < 0.5 ng/ml, in 4 patients 0.5 to 1.5 ng/ml. In 2 patients we noted biochemical relapse. Transrectal implantation was very well tolerated. Grade 3 acute urinary toxicity occurred in 1 patient. We noted no Grade 2 or higher acute gastrointestinal toxicity. One patient developed a Grade 3 late urinary toxicity. No patient showed late gastrointestinal side effects. All 140 dose-volume histograms for 3D HDR brachytherapy were analyzed. CONCLUSIONS: The new 3D HDR brachytherapy technique, combined with 3D external irradiation and androgen deprivation, is a feasible, so far well-tolerated and effective treatment in the short-time follow-up of median 18 months.     

Initial comparison of inverse optimization, modified peripheral technique, and geometric optimization as real-time intraoperative computer planning options for permanent seed implantation of the prostate

PURPOSE: Comparison of inverse optimization (IO) to modified peripheral (MP) and geometric optimization (GO) intraoperative computer planning options for permanent seed implantation (PSI) of the prostate. METHODS AND MATERIALS: One hundred ten patients underwent PSI with iodine-125. Three computer planning options were compared including MP loading, GO, and IO. Preimplant dose goals (prescribed dose [PD] of 144 Gy) and normal tissue constraints were determined at the outset by the participating physicians before intraoperative computer planning. A single computer planning system was used for this comparison. Postimplant dosimetry was performed at 4-5 weeks and compared for V(100) and D(90), urethral V(150), and rectal V(110) of the PD. Acute urinary morbidity was evaluated and compared. RESULTS: All three options achieved a similar preimplant median V(100) (97%). The median number of needles and seeds implanted was greater with GO (29, 75) compared to MP (16, 66) and IO (17, 66) (p<0.0001 and p=0.0024, respectively). Postimplant dosimetry showed that IO achieved a higher percentage with V(100) >95% of the PD in multivariate analysis (p=0.04) and a lower percentage postimplant D(90) <140 Gy (7%) than for MP/GO (26%) (p = 0.01). IO predicted for lower urethral dose (p=0.0169), despite a higher median D(90) (169 Gy) than either MP (159 Gy) or GO (151 Gy) (p = 0.0025). The median percentage V(150) urethra for IO was 8% vs. 16% for MP and 23% for GO (p = 0.0005). With a median followup time of 6 months, acute Grade 2 urinary symptoms were higher with GO (81%) vs. MP (36%) and IO (53%) (p = 0.0019). CONCLUSIONS: Dosimetric outcomes for IO compare favorably to either MP or GO when performed in real time for PSI. In contrast to GO, IO and MP demonstrated excellent correlation between the intraoperative and postoperative plans while using fewer total and interior placed needles and seeds. IO appears feasible as an alternative intraoperative planning solution for PSI.     

Equivalent uniform dose, D(90), and V(100) correlation with biochemical control after low-dose-rate prostate brachytherapy for clinically low-risk prostate cancer

PURPOSE: To assess the correlation of postimplant dosimetric quantifiers with biochemical control of prostate cancer after low-dose-rate brachytherapy. MATERIALS AND METHODS: Generalized equivalent uniform dose (EUD), dose in Gy to 90% of the prostate gland (D(90)), and percentage of the prostate receiving 100% of the prescribed dose (V(100)) were calculated from the postimplant dose-volume histogram (DVH) for 140 patients undergoing low-dose-rate prostate brachytherapy (LDRPB) monotherapy from 1997 to 2003 at Duke University and the Durham VA Medical Center. Biochemical recurrence was defined according to the American Society for Therapeutic Radiology and Oncology consensus definition. RESULTS: Median followup after LDRPB was 50 months. There was a 7% biochemical recurrence rate (10/140) at last clinical followup. The median EUD was 167 Gy (range, 41-245). The median D(90) was 139 Gy (range, 45-203). The median V(100) was 88% (range, 44-100). The overall 5-year biochemical recurrence-free survival (bRFS) was 94.2%. The 5-year bRFS was 100% for EUD> or =167 Gy and 89.4% for EUD <167 Gy (p=0.008); 100% for D(90) > or =140 Gy and 90.4% for D(90) <140 Gy (p=0.020); 100% for V(100) > or =88%; and 90.3% for V(100) <88% (p=0.017). There was no statistically significant correlation between any of these factors and overall survival. CONCLUSIONS: In our series of 140 patients with low-risk prostate cancer treated with LDRPB alone, we observed a statistically significant correlation between EUD, D(90), and V(100) and bRFS. The generalized EUD, a calculated value that incorporates the entire prostate DVH, appears to be at least as well correlated with bRFS as D(90) or V(100), and may more completely represent the totality of the dose distribution.     

Androgen deprivation-mediated cytoreduction before interstitial brachytherapy for prostate cancer does not abrogate the elevated risk of urinary morbidity associated with larger initial prostate volume

PURPOSE: We examined whether prostate volume reduction after a short course of androgen deprivation (AD) lowered the risks of acute and chronic urinary morbidity related to radioactive seed implantation for low-risk prostate cancer. METHODS AND MATERIALS: Eighty-one patients received AD for cytoreduction before interstitial brachytherapy alone. Urinary morbidity was carefully assessed for all patients during a median followup of 53 (range, 23-78) months after treatment. Outcomes were then compared with those of a control group of 81 patients who were matched 1:1 based on identical prostate volume measured at the time of radioactive seed implant, but who had not received AD. RESULTS: Despite effective cytoreduction (median, 30% prostate volume reduction) with AD, prolonged catheterization was required significantly more often for patients who had received AD when compared with the control group of patients who were implanted at identical prostate volumes but who had not received AD (27% vs. 9%, p = 0.02). This finding remained statistically significant on multivariate analysis (p = 0.04). Surgical intervention (9% vs. 4%, p = 0.09) and subsequent urinary incontinence (4% vs. 1%, p = 0.16) were also more frequent among patients who had received AD when compared with implant volume-matched controls. CONCLUSIONS: Patients who achieved smaller prostate volumes through the use of AD maintained a significantly elevated risk (threefold) for urinary complications, commensurate with their initially large prostate volume, when compared with a control group of patients who were implanted at identical prostate volumes but who had not received AD. Therefore, patients presenting with larger prostate glands that would warrant a short course of AD before implant should be counseled accordingly when discussing options for local therapy.     

Salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy

PURPOSE: To determine the toxicity and clinical outcome of salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy. METHODS AND MATERIALS: Twenty-one patients underwent (103)Pd salvage brachytherapy (median minimum peripheral dose, 90Gy) after local failure after external beam radiation (median dose, 66.6Gy) from 1/21/1998 to 4/5/2005. The median age was 72 years. Six patients had prior transurethral resection of the prostate. The median Gleason score was 7 and the median preimplant prostate-specific antigen was 3.8. Twelve patients received concurrent androgen ablation with prostate brachytherapy. Biochemical failure was defined as three consecutive rises in prostate-specific antigen scored at the call date, initiation of hormone therapy, or clinical failure. Toxicity was defined according to the National Cancer Institute common toxicity criteria and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. RESULTS: With a median followup of 36 months, the actuarial 3-year and 5-year overall survival rates were 81% and 81%, and the biochemical failure-free survival rates were 94% and 38%, respectively. There was no significant difference in biochemical failure-free survival (p=0.98) and overall survival (p=0.13) for patients who had androgen ablation. Four patients developed biochemical failure and 1 patient developed distant metastasis at 59 months from treatment. Four patients had Grade 2 genitourinary adverse events, 2 patients had Grade 1 genitourinary adverse events, and 1 patient had a Grade 2 gastrointestinal adverse event. There were no Grade 3 or higher adverse events. All three deaths were secondary to other medical comorbidities. CONCLUSIONS: Salvage prostate brachytherapy after external beam radiation failure can be safely performed with acceptable biochemical control. This treatment option should be considered for patients who have prolonged life expectancy after localized external beam radiation failure.     

High-dose-rate interstitial brachytherapy for gynecologic malignancies

PURPOSE: The study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB). METHODS AND MATERIALS: Between 1998 and 2004, 16 previously unirradiated patients with locally advanced cervical and vaginal cancer not suitable for intracavitary brachytherapy because of distorted anatomy or extensive vaginal disease were treated with HDRB in combination with external beam radiotherapy. All patients received whole pelvis external beam radiation therapy (EBRT) followed by interstitial implantation. The median whole pelvis external beam dose was 45 Gy (range, 39.6-50.4 Gy) with 11 patients receiving parametrial boost to a median dose of 9 Gy. Twelve (75%) of these patients received chemotherapy concurrent with external beam. All patients received a single HDRB procedure using a modified Syed-Neblett template. A CT scan was performed postimplant for needle placement verification and treatment planning purpose. Dose was prescribed to the tumor volume based on the radiographic and clinical examination. All patients received 18.75 Gy in five fractions delivered twice daily. The median followup was 25 months (6-69 months). RESULTS: Median cumulative biologic effective dose (EBRT+HDRB) to tumor volume was 78.9 Gy10 with the range of 72.5-85.2Gy10. Median cumulative biologic effective dose for the rectum and bladder were 99.4 Gy3 (range, 79.6-107.8 Gy3) and 96.4 Gy3 (range, 78.3-105.3 Gy3), respectively. Complete response was achieved in 13 (81%) patients with 3 patients having persistent disease. Five of these 13 patients developed recurrence at a median time of 14 months (distant in 4 and local and distant in 1). The 5-year actuarial local control and cause-specific survival were 75% and 64%, respectively. In subset analysis, 5-year actuarial local control was 63% for cervical cancer patients and 100% for vaginal cancer patients. No patient had acute Grade 3 or 4 morbidity. Grade 3 or 4 delayed morbidity resulting from treatment occurred in 1 patient with 5-year actuarial rate of 7%. Three patients had late Grade 2 rectal morbidity and 1 patient had Grade 2 small bowel morbidity. CONCLUSIONS: Our series suggests that single interstitial implantation procedure with five fractions of 3.75 Gy each to target volume is an effective and safe fractionation schedule. The integration of imaging modality helps in decreasing dose to the critical organs. Additional patients and followup are ongoing to determine the long-term efficacy of this approach.     

Urinary morbidity in brachytherapy patients with median lobe hyperplasia

PURPOSE: To investigate clinical course of prostate brachytherapy patients with radiographic evidence of median lobe hyperplasia (MLH). METHODS AND MATERIALS: Fifteen patients with median lobe hyperplasia were identified during our routine brachytherapy practice and implanted between June 1998 and March 2000, representing approximately 6% of the 245 brachytherapy patients treated during that time. Each patient was contacted at the time of this report preparation to update postimplant morbidity information, with follow-up ranging from 6 to 30 months (median: 18 months). RESULTS: Three of the 15 patients developed acute, postimplant urinary retention. The preimplant prostate volume, dMLH, and preimplant AUA scores were similar between patients who did or did not develop prolonged urinary retention. Compared with a control group of 62 control patients treated during a similar time interval at the University of Washington, patients with MLH had significantly higher AUA scores at last follow-up. There was no correlation between the change in AUA scores at last follow-up. CONCLUSIONS: Based on the data reported here, we consider MLH to be a weak contraindication to prostate brachytherapy. Considering that even patients with prolonged retention have gradually improved spontaneously, we do not advocate prophylactic prebrachytherapy resection of hypertrophic tissue in MLH patients.     

The utility of transition zone index in predicting acute urinary morbidity after 125I prostate brachytherapy

PURPOSE: Acute urinary morbidity after prostate brachytherapy is common and, although usually self-limited, can be distressing to the patient, especially if acute urinary retention (AUR) develops. We undertook to determine whether prospective measurement of the transition zone index would be predictive of either urinary retention or the severity of urinary symptoms after brachytherapy. METHODS AND MATERIALS: One hundred men undergoing transperineal interstitial permanent prostate brachytherapy (TIPPB) with 125I underwent transrectal ultrasound before the procedure to measure prostate and transition zone (TZ) volumes. TZ index was calculated as TZ volume divided by total prostate volume. TIPPB was performed between July 2000 and January 2002. Patients were observed for 1, 3, or 6 months with an International Prostate Symptom Score (IPSS) at each visit. alpha-Blockers were prescribed prophylactically in all patients. Postimplant dosimetry was performed at 1 month by using CT/MRI fusion for all patients. RESULTS: The mean patient age was 65.1 years (range, 46-77 years). There were 59 T1c tumors and 41 T2a tumors. The Gleason score was 6 in 86% of patients, with 3% being Gleason 4 or 5 and 11% Gleason 7. The mean baseline IPSS was 7.4, with the mean at 1 month being 17.3; at 3 months, 14.4; and at 6 months, 11.3. Baseline IPSS was the only factor predictive of IPSS at 1 and 3 months after TIPPB. Neoadjuvant androgen deprivation was used for 26% of men for 2-6 months to reduce prostate size before the procedure. AUR developed in 17%. In univariate analysis, prior hormone therapy (p = 0.002), duration of hormone therapy (p = 0.005), TZ index (p = 0.014), number of seeds implanted (p = 0.016), T stage (p = 0.035), percentage of the prostate volume receiving at least the full prescribed dose (V100, p = 0.036), percentage of the prostate volume receiving > 200% of the prescribed dose (V200, p = 0.037), and prostate volume (p = 0.038) were all predictive of AUR. When the TZ index was divided into quartiles, the risk of AUR was 4%, 16%, 20%, and 28% (p = 0.032). However, in multivariate analysis, TZ index was no longer predictive of AUR. CONCLUSIONS: Baseline urinary function is the only factor predictive of symptom scores at 1 and 3 months after brachytherapy. TZ index, initial prostate volume, and use of neoadjuvant hormones are interrelated and are all predictive of AUR in univariate analysis, but in multivariate analysis, TZ index is not an independent prognostic factor.     

Two-step transurethral surgery of the prostate and permanent implant brachytherapy for patients with lower urinary tract symptoms and low- to intermediate-risk prostate cancer

PurposeProstate brachytherapy is an increasingly used treatment option for low- to intermediate-risk prostate cancer (PCa). However, patients with preexisting lower urinary tract symptoms (LUTS) and PCa, who would otherwise be good brachytherapy candidates, are often contraindicated because of the risk of postoperative urinary morbidity. We report our clinical experience with limited transurethral resection of the prostate (LTURP) and/or transurethral incision of the prostate (TUIP) months before brachytherapy to treat patients with LUTS and low- to intermediate-risk PCa.Methods and MaterialsOf 258 men undergoing prostate brachytherapy at our institution between 1998 and 2011, 42 were treated with planned LTURP and/or TUIP well before (mean, 5.7 months) seed implantation. Transurethral surgery was considered before brachytherapy for patients who at presentation required α-blocker therapy for LUTS, had an International Prostate Symptom Score greater than 14 off α-blockers, or had an elevated postvoid residual (>100 mL). Patients only proceeded to brachytherapy once LUTS resolved.ResultsAll 42 patients in our series underwent TUIP (25), LTURP (7), or TUIP/LTURP (10) with mean 5.7 months before prostate brachytherapy for low- or intermediate-risk PCa. Mean International Prostate Symptom Score, peak flow rate, and postvoid residual significantly improved after transurethral surgery, and improvement persisted at the latest followup. No patient developed retention, urethral necrosis, or urinary incontinence after transurethral surgery or brachytherapy (median followup, 39 months and range, 1–121).ConclusionsPlanned LTURP and/or TUIP more than 4 months before brachytherapy is a safe and effective treatment strategy for men with LUTS and low- to intermediate-risk PCa.     

High-dose-rate brachytherapy in combination with conformal external beam radiotherapy in the treatment of prostate cancer

PurposeTo report long-term outcomes for treatment of prostate cancer using dose escalation with high-dose-rate (HDR) brachytherapy and 3-dimensional conformal external beam radiotherapy (3DCRT), and compare them with outcomes for treatment of prostate cancer with 3DCRT alone at the same institution.Methods and MaterialsFrom 1998 to 2003, 587 patients were treated for clinically localized prostate cancer. Patients received either 3DCRT (median, 46 Gy) with a single HDR brachytherapy implant (196 patients) delivering a fractionated dose of 18 Gy (combined group) or 3DCRT (median, 70 Gy; 387 patients; “3DCRT alone”). There were 41.9% patients with intermediate-risk and 42.6% with high-risk disease. In all, 441 patients (75.1%) received neoadjuvant and 116 patients (19.8%) received adjuvant androgen deprivation therapy. The American Society of Therapeutic Radiology and Oncology Phoenix definition for biochemical failure was used.ResultsThe median followup was 5.5 years. The 5- and 7-year biochemical control (BC) rates were 82.5% and 80.3%, respectively, for the combined group and 81.3% and 71%, respectively, for 3DCRT alone; for overall survival, they were 91.9% and 89.5% vs. 88.7% and 86.2%, respectively, whereas for cause-specific survival, they were 96.9% and 96.1% vs. 97.6% and 96.2%, respectively. Cox proportional hazard regression analysis for BC revealed that low Gleason grade, HDR brachytherapy combined with 3DCRT, and adjuvant androgen deprivation therapy were significant in predicting BC. Radiation Therapy Oncology Group Grade 3 late urinary and rectal morbidity rates were 7.1% and 0%, respectively. No Grade ≥4 reactions were detected.ConclusionsHDR brachytherapy combined with 3DCRT was associated with improved BC and minimal toxicity in patients with unfavorable prostate cancer compared with conventional 3DCRT.     

Protocol-based image-guided salvage brachytherapy

Purpose

To assess the overall clinical outcome of protocol-based image-guided salvage pulsed-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy failure particularly regarding feasibility and side effects.

Patients and methods

Eighteen consecutive patients with locally recurrent prostate cancer (median age, 69 years) were treated during 2005–2011 with interstitial PDR brachytherapy (PDR-BT) as salvage brachytherapy after radiotherapy failure. The treatment schedule was PDR-BT two times with 30 Gy (pulse dose 0.6 Gy/h, 24 h per day) corresponding to a total dose of 60 Gy. Dose volume adaptation was performed with the aim of optimal coverage of the whole prostate (V₁₀₀ >?95?%) simultaneously respecting the protocol-based dose volume constraints for the urethra (D_0.1 cc <?130?%) and the rectum (D_2 cc <?50–60?%) taking into account the previous radiation therapy. Local relapse after radiotherapy (external beam irradiation, brachytherapy with J-125 seeds or combination) was confirmed mostly via choline-PET and increased PSA levels. The primary endpoint was treatment-related late toxicities—particularly proctitis, anal incontinence, cystitis, urinary incontinence, urinary frequency/urgency, and urinary retention according to the Common Toxicity Criteria. The secondary endpoint was PSA-recurrence-free survival.

Results

We registered urinary toxicities only. Grade 2 and grade 3 toxicities were observed in up to 11.1?% (2/18) and 16.7?% (3/18) of patients, respectively. The most frequent late-event grade 3 toxicity was urinary retention in 17?% (3/18) of patients. No late gastrointestinal side effects occurred. The biochemical PSA-recurrence-free survival probability at 3 years was 57.1?%. The overall survival at 3 years was 88.9?%; 22?% (4/18) of patients developed metastases. The median follow-up time for all patients after salvage BT was 21 months (range, 8–77 months).

Conclusion

Salvage PDR-brachytherapy of the prostate following local failure after radiation therapy is a treatment option with a low rate of genitourinary side effects and no late gastrointestinal side effects. The treatment efficacy in the first 3 years is promising.