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Background and Purpose: The effect of predominating Gleason grade (3+4 versus 4+3) in Gleason sum score (GS) 7 prostate cancer (PCa) on brachytherapy outcomes is unclear. The 10 year experience of permanent brachytherapy monotherapy at a single UK centre for GS 7, intermediate risk (Memorial Sloan-Kettering model), PSA < or = 10 ng/ml, localised PCa is reported., Materials and Methods: Between 1995 and 2004, the outcomes of 187 patients with GS 7 PCa (PSA < or = 10 ng/ml) were analysed from a cohort of 1298 men treated with permanent Iodine-125 prostate brachytherapy, including PSA relapse-free survival (PSA-RFS)., Results: Median follow-up was 5.0 years (range 2.0-10.1 years). One patient has died of PCa. At 10 years, PSA-RFS was 82.4%/78% (ASTRO consensus and nadir +2 definitions). For GS 3+4, 5 year PSA-RFS was 86.7%/87.9% and for GS 4+3: 85.2%/96.6% respectively, with no significant difference between groups. Five year PSA-RFS (ASTRO) of 92.6% was seen for D(90) > or = 140 Gy (50% total), compared with 77.0% below 140 Gy (p=0.08)., Conclusions: Iodine-125 brachytherapy monotherapy achieved good rates of medium term biochemical control in GS 7, intermediate risk localised PCa patients. There was a trend to improved outcomes in men with a D90 in excess of 140 Gy., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: This study reports the 10-year experience of permanent brachytherapy monotherapy at a single UK center., Methods and Materials: Between March 1995 and September 2004, 1,298 patients underwent trans-rectal ultrasound (TRUS) planned transperineal brachytherapy delivering 145 Gy using I-125. No patient received supplemental external beam; 44.2% received neoadjuvant hormones. In 688, CT postimplant dosimetry was available. Outcome data were analyzed in terms of overall survival (OS), disease specific survival (DSS), and PSA relapse-free survival (PSA-RFS)., Results: The mean age was 62.9 (range, 34-83) years. Median follow-up was 4.9 years (range, 2.03-11.7 years). OS and DSS were 85% and 95%, respectively, at 10 years. Twenty-one patients died from prostate cancer (1.6%) and 34 (2.5%) from unrelated causes. Seventy-four (5.7%) developed evidence of clinical failure. Overall PSA-RFS was 79.9% and 72.1% at 10 years (American Society for Therapeutic Radiology and Oncology [ASTRO] and Nadir+2 definitions, respectively). Higher presenting PSA or Gleason score and use of neoadjuvant hormones were associated with an increased risk of biochemical failure (p <0.01). Biochemical control was achieved in 86.4%, 76.7%, and 60.6% (ASTRO) and 72.3%, 73.5%, and 57.6% (Nadir+2) of patients in low-, intermediate-, and high-risk groups, respectively. Biochemical control was achieved in 88% of patients with D(90) > or =140 Gy and in 78% of patients with D(90) <140 Gy (p <0.01)., Conclusions: I-125 brachytherapy alone achieved excellent rates of medium-term biochemical control in both low- and selected intermediate-risk localized prostate cancer patients. Postimplant dosimetry improved with experience and longer follow-up, confirming the relationship of D(90) with biochemical control.

Aims: To report the results of I(125) prostate brachytherapy from a central, prospectively collected database of three UK institutions., Materials and Methods: All patients treated with I(125) permanent prostate brachytherapy at the Christie Hospital, Manchester (CHM), Cookridge Hospital, Leeds (CKL) and Mount Vernon Hospital, Northwood, London (MVL) since 2003 have been prospectively registered on a detailed central database. Patient, tumour, pre- and post-implant dosimetry data have been recorded. Urinary toxicity as assessed by the International Prostate Symptom Score, catheterisation and urinary stricture rates after implant have been documented and biochemical failure determined, using both the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and the Phoenix (nadir + 2 ng/ml) definition., Results: In total, 1535 patients were registered on the database between January 2003 and October 2006, including 432 from CHM, 926 from CKL and 177 from MVL, with a median follow-up of 21 months (range 1-56). Patient and tumour characteristics were similar at all centres. Pre-implant dose indices were comparable between centres, except for the V150, with median values of 51.9, 64.3 and 69.8% at CHM, CKL and MVL, respectively. Median post-implant dose parameters were lower than pre-planned constraints by up to 33.0% at each centre for all values, except at CKL where the V200 was 23.9% higher. The International Prostate Symptom Score increased from a median of 5 at baseline to 18, 6 weeks after implant, but was not significantly different to baseline values by 12 months. Nine per cent of men required catheterisation after implant for a median duration of 53 days, but urinary stricture rates remained low at 1%. Neoadjuvant hormonal manipulation was used in 228 men (15%) for downsizing and 159 (10%) for intermediate/high-risk disease. Collated biochemical failure rates were low at this point of follow-up, with actuarial 2-year ASTRO and Phoenix biochemical failure-free survival rates of 94.4 and 94.5%, respectively, consistent with other large single centre reports. When post-implant dosimetric factors were assessed for a relationship to biochemical failure, no indices consistently predicted for improved ASTRO and Phoenix biochemical failure-free survival rates., Conclusions: This ongoing collaboration shows that with limited infrastructure (a single industry-sponsored data manager), a large multi-institutional database estimated to represent one-third of implants carried out in the UK during this time can be developed. Patient selection was similar across all centres and adhered to published guidelines. Early biochemical and toxicity outcomes confirm the efficacy and tolerability of I(125) prostate brachytherapy in a large cohort of patients. A further analysis is planned.

Background and Purpose: To prospectively evaluate long-term urinary, bowel and sexual function after I-125 brachytherapy for localised prostate cancer using patient administered validated Quality of Life (QoL) instruments., Materials and Methods: Between March 1995 and March 2004, 673 men underwent brachytherapy and recorded urinary symptoms prospectively using the International Prostate Symptom Score (IPSS). In addition, in a subgroup of 116 patients, the Expanded Prostate Cancer Index Composite (EPIC) was used to record QoL information on urinary, bowel and sexual function before treatment and at regular time intervals for at least two years., Results: Initially, there was a sharp rise in urinary symptoms which was most marked within the first three months. Scores then resolved slowly and returned to within one or two units of pre-treatment level at one year. Subsequently, there was no significant deterioration in urinary symptoms up to nine years following brachytherapy. Few had significant bowel symptoms. Sexual function deteriorated initially and then improved but failed to return to pre-treatment levels by two years. Patients requiring neo-adjuvant hormones experienced significantly more dysfunction., Conclusions: After an initial period of mild to moderate urinary symptoms prostate brachytherapy is well tolerated with relatively little deterioration in long-term quality of life. Long-term reduction in sexual function may be seen particularly in those requiring hormones.

Objective: The use of prostate brachytherapy (BT) in the management of prostate cancer is increasing. BT is often chosen because of its perceived lower toxicity when compared with other radical therapy options. Rarely however serious complications can occur. One such complication is recto-urethral fistula (RUF). We report the incidence of RUF following BT at our centre and review the potential factors in fistula development., Method: A prospectively collected database was used to identify cases of RUF among 1455 patients treated with prostate BT at a single UK centre with at least 2 years of follow up. This included patients treated with BT monotherapy, as well as those treated with BT combined with external beam radiotherapy and BT used as salvage as all these groups have a higher incidence of RUF. Implant dose and volume characteristics for those patients, their co-morbidities and history of endoscopic procedures were recorded., Results: Recto-urethral fistula was identified in three (0.2%) patients, occurring at 19-27 months following BT. All these patients had BT monotherapy. All three patients had rectal symptoms after their BT and had been investigated with endoscopy and low rectal biopsy. Subsequent surgical management with faecal and/or urinary diversion was required. On review of patients' BT details, radiation dose and volume parameters were higher on the postprocedure CT calculations than had been suggested by the preimplant plan. No other predisposing risk factors for RUF were identified., Conclusion: The incidence of RUF in our population is low. RUF following BT has been associated with rectal biopsy in previous series and this is confirmed in our report. Gastrointestinal specialists should not perform biopsy of the anterior rectum in patients who have had BT unless there is a very high clinical suspicion of malignancy.

Purpose: To report the side effects and complications after I-125 seeds prostate implant after 8.5 years experience., Methods and Materials: Six hundred and sixty seven (667) patients were treated between March 1995 and December 2001. The median follow up is 31 months with a maximum of 98.2 months. Morbidity data were collected from a review of patient case-notes. Patients also provided prospective data on urinary symptoms using the International Prostate Symptom Score (IPSS) scoring chart before treatment and at regular follow up. Patients were also sent a questionnaire detailing symptoms and side effects following their brachytherapy. This enabled them to record urinary, bowel and sexual function side effects independently. Logistic regression analysis was carried out to identify the risk of catheterisation in relation to the pre-implant prostate volume and potential implant factors such as the number of seeds and needles and implant dose., Result: The urinary symptom score rises in the first few months after implantation and returns to within one or two points of the pre-treatment score within one year. Nine patients reported incontinence prior to treatment and 15, 12 and 10 patients reported incontinence 6, 12 and 24 months after treatment, respectively. Catheterisation was reported in 97 (14.5%) patients. At six months 84.9% of patients reported no change in bowel function and 78.9% at 12 months. 6.4% of patients complained of some increased bowel frequency at 6 months and 5.7% at 12 months. 402 (77.2%) patients reported being fully potent before treatment and that this fell to 32.4% after treatment. Logistic regression showed that the most significant factors which correlate with the probability of catheterisation are the pre-treatment prostate volume and the number of seeds and needles implanted., Conclusion: The side effects and complications after prostate brachytherapy as reported here and elsewhere confirm that the treatment is not only convenient but also has a low risk of serious long term side effects.

Background and Purpose: In 1998 Stock and Stone demonstrated a dose response relationship correlating D90 with probability of biochemical control and showed that a D90 of 140 Gy is a highly significant factor in predicting PSA relapse free survival (PSA-RFS). Although, a mean D90 of over 140 Gy was achieved in our series, there is nevertheless a normal distribution with 20% of patients achieving a D90 of less than 120 Gy. We have analysed the possible causes for the low D90 and the impact on outcome., Patients and Methods: Prospective data from 667 patients treated between 1995 and 2001 by I-125 seeds prostate implant as monotherapy were analysed. Post-implant dosimetry was performed on 413 patients. D90 and other indices were calculated for each patient. Statistical analysis was performed on D90 dose to identify the correlation that would predict the 8.2 years PSA relapse free survival as defined by the American Society for Therapeutic Radiology and Oncology (ASTRO)., Results: Correlation between D90 and outcome shows no significant difference for the whole population between those who receive greater or less than 140 Gy (P=0.43) and there was also no difference for those receiving more or less than 130 Gy (P=0.14). Subgroup analysis by risk group, however, showed that for low risk patients there was a significant correlation between D90 and PSA control (P<0.01). Although, post-implant dosimetry was performed 6-8 weeks after brachytherapy, post-implant CT still showed variable levels of oedema compared with the pre-implant ultrasound. A statistically significant relationship was shown between D90 and the ratio between CT and ultrasound volume (P<0.01) which suggests that some low D90s may be related to persistent oedema at the time of calculation. Segmental analysis of a subgroup of 32 patients showed that the dose was most often deficient in the anterior basal segment of the gland., Conclusions: D90 was found to be a good discriminator for those with low risk where failure to achieve local control is likely to be the dominant cause of PSA failure. No significant dose response relationship between D90 and PSA was found in the intermediate and high-risk population of patients. This could be due to (1) the presence of oedema or discrepancy between pre- and post-implant volumes causing a low D90, (2) the possibility that the underdosed area could be situated where there is unlikely to be tumour, (3) the fact that biochemical control does not equate to local control because some patients fail outside the prostate, particularly in the high and intermediate risk patients, (4) if D90 is a good discriminator only for low risk patients, the absence of a dose response correlation in this series which contained 53.8% intermediate and high risk patients could be related to case mix.

Background and Purpose: Many patients with localised prostate cancer present with symptoms of benign prostatic hypertrophy (BPH) and require neoadjuvant hormone therapy to shrink the gland before brachytherapy. The impact of this hormone therapy has been evaluated in 667 patients treated with Iodine seed monotherapy., Patients and Methods: Prospective data from 667 patients treated between 1995 and 2001 by I-125 seeds prostate implant as monotherapy were analysed. The mean age was 63 years (42--77 years). Three hundred and forty-six (51.9%) patients had a short course of neo adjuvant hormone therapy and 321 (49.1%) did not. The prescribed minimum peripheral dose was 145 Gy (TG 43). Patients were followed up to a maximum of 8.2 years and a minimum of 18 months. Statistical analysis was performed to identify factors that would predict PSA relapse-free survival (PSA-RFS) defined by the American Society for Therapeutic Radiology and Oncology (ASTRO)., Results: Overall the PSA relapse-free survival is 76.1 and 72.6% for patient cohorts being on pre-treatment hormones and not, respectively (P=0.107). Subdivided into risk groups the low risk group showed 92.5% PSA-RFS with hormones and 75.1% without (P=0.327). The intermediate group 75.7% with hormones and 72.9% without (P=0.148) and for the high-risk group 51.1% with and 51.1% without hormones (P=0.942). Evaluation of post-implant dosimetry in patients with and without hormone therapy showed that the D90 for those who received hormone therapy was 130.8 Gy compared with 145.1 Gy for those who did not (P<0.001). This may be related to the degree of oedema at the time of post-implant dosimetry. The CT to ultrasound prostate volume ratio was 1.17 for patients who received hormone therapy and 0.98 for those who did not (P<0.001). It is suggested that in the interval between stopping hormone therapy and doing post-implant dosimetry there was an increase in prostate volume, which results in a lower D90. Significant correlation was found between D90 and prostate volume on post-implant CT dosimetry with higher D90s for small volume prostates (P<0.001)., Conclusions: Overall hormone therapy had no significant effect on outcome. The apparent lower D90 in hormone treated patients may be related to a change in volume between pre-implant and post-implant dosimetry.

Purpose: To investigate the variability of prostate implant quality indices between three different methods of calculating the post-implant dose distribution., Methods and Materials: In a study of 9 permanent prostate implant patients, post-implant dosimetry was carried out using three methods of identifying seed positions within the prostate volume: (1) prostate volumes defined by transrectal ultrasound (TRUS) immediately following implant were registered with shift-film defined seed positions, (2) seeds were identified directly from the post-implant TRUS images, and (3) CT was used to define seed positions and prostate volumes from images acquired at 41-65 days post-implant. For each method, the volume of prostate receiving 90%, 100%, and 150% of the prescribed dose (V90, V100, V150) and the dose delivered to 90% of the prostate volume (D90) were calculated., Results: Post-implant TRUS volumes were within 15% of the preimplant TRUS volumes in 8 of the 9 patients investigated. The post-implant CT volume was within 15% of the preimplant (TRUS) volume in only 3 of the 9 cases. The value of the dosimetry parameters was dependent on the method used and varied by 5-25% for V90, 5-30% for V100, 42-134% for V150, and 9-60% for D90. No simple relationship was found between change in volume and the resultant change in dosimetry parameter. Differences in dosimetry parameters due to source localization uncertainties was found to be small (< or = 10% for V100) when comparing methods (1) and (2)., Conclusions: There are many uncertainties in the calculation of parameters that are commonly used to describe the quality of a permanent prostate implant. Differences in the parameters calculated were most likely a result of a combination of factors including uncertainties in delineating the prostate with different imaging modalities, differences in source identification techniques, and intraobserver variability.

Objective: To report the clinical outcome after permanent implantation of (125)iodine seeds (brachytherapy) for early prostate cancer, after 8.2 years of follow-up., Patients and Methods: Between March 1995 and December 2001, 667 men (mean age 63 years, range 42-77) were treated with brachytherapy at the one cancer centre; 346 (51.9%) had a short course of neoadjuvant hormone therapy. The prescribed minimum peripheral dose was 145 Gy. No patient received external beam radiation., Results: The median (range) follow-up was 31 (18-98.2) months; 41 patients were lost to follow-up. The actuarial biochemical relapse-free survival was 74.9%; 100 patients had biochemical relapse (international definition). In all, 20 patients had clinical relapse, and 24 died (10 from prostate cancer). The prostate-specific antigen (PSA) relapse-free survival was 78.3%, 66.5% and 56.4% for patients with Gleason scores of <7, 7 and > 7, respectively, and was 81.4%, 69.8% and 36.3% for those with PSA levels of <10, 10-20 and > 20 ng/mL, respectively (both P < 0.001). There was a strong cohort effect depending on year of implant, with progressive annual improvements in relapse-free survival (P < 0.001). Hormone therapy, tumour stage, prostate volume before implantation, age and D90 dose had no significant effect on the outcome., Conclusion: The overall relapse-free survival for all patients was 75%; the initial PSA, Gleason score and risk group were significant factors predicting the outcome. Increasing clinical experience was associated with a better outcome but neoadjuvant hormone therapy had no effect.

Purpose: A number of reports of (125)I seed migration to the lungs after prostate brachytherapy have been published. There are, however, very limited data available on how to reduce the risk of this event. The purpose of the present report is to determine whether seed embolization to the lungs can be minimized by using stranded seeds alone for brachytherapy., Methods and Materials: Between December 2001 and December 2002, 238 patients with early prostate cancer were treated with prostate brachytherapy as monotherapy using (125)I stranded seeds (RAPIDStrand) exclusively. All patients had fluoroscopy during the implant and immediate postimplant radiographs of the pelvis. A sample of 100 patients had chest radiographs performed, on average, 55 days after implant. To determine the ease, or lack of ease, with which these (125)I seeds could be visualized, 4 patients who did not have prostate cancer and who were having routine chest radiographs as part of their management for other cancers consented to have posteroanterior and lateral radiographs performed with inactive (125)I seeds taped to the skin of the thorax. All radiographs were reviewed by a single radiologist., Results: The number of seeds noted on the postimplant radiographs corresponded to the number of implanted seeds in all 238 cases: There was, therefore, no evidence of seed embolization immediately postimplant. On review of the 100 chest radiographs, no embolized seeds were found., Conclusion: No evidence of seed embolization was observed with the use of stranded (125)I seeds as used for prostate brachytherapy.

Purpose: An analysis of computed tomography (CT)-based dosimetry was performed to evaluate the variability of different observers' judgements in marking the prostate gland on CT films, and its effect on the parameters that characterise the prostate implantation quality. Accuracy of data entry by the first author in the process of dosimetry procedure has also been evaluated., Materials and Methods: Four observers were asked to evaluate the prostate volume on CT films for six different patients. Each observer repeated the evaluation six times. The sample of patients has a prostate volume in the range of 21.4-42.0 cc derived from transrectal ultrasound volume study. After an average period of 6 weeks of the I-125 implantation, all patients had CT scans. CT-based post-implant dosimetry was performed and the dose volume histograms DVHs were calculated to report the re-constructed prostate volume, Vp100, Vp150, Vp90 and D90. Comparison between the four observers' output was performed., Results: Comparison between the four observers shows that each observer has a different way of estimating the prostate on CT films. Observers' precision also varies according to the prostate volume and the image quality. This can cause a variation in the resulting D90 value by up to 50%. Analysis of data entry shows a high degree of accuracy. The error of digitizing the prostate is +/-0.19 cc. This is correlated to an error of +/-0.78 Gy of the D90., Conclusion: The evaluation of prostate gland volume on CT films varies between different observers. This has an effect on the dosimetric indices that characterise the implant quality in particular the D90.

Objective: To report the short-term morbidity and acceptability of the first 50 patients treated with the percutaneous implantation of radioactive iodine seeds for localized carcinoma of the prostate at the Cookridge Hospital., Patients and Methods: Fifty patients were treated with transrectal ultrasonography-guided percutaneous implants with radioactive (125I) iodine seeds for localized carcinoma of the prostate. The mean hospital stay was 36 h and most patients were able to return to work or normal activity within one week of implantation., Results: All patients developed urethritis which was most marked within the first 3 months of treatment; 8% of patients developed acute retention which resolved after temporary catheterization. At 3 months, 36% of patients still had moderate frequency and 18% moderate dysuria, but by 12 months these had resolved and only 5% of patients still complained of moderate nocturia. There were no cases of incontinence. The incidence of proctitis was very low, with only 2% still complaining of moderate symptoms at one year. Of those potent before implantation, 72% retained potency at one year., Conclusions: Although it is too early to comment either on late morbidity or on outcome, the results of this study show a side-effect profile similar to that reported by other centres using the same technique.