Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder.

AIM: To characterize purinergic signaling in overactive bladder (OAB). METHODS: Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. RESULTS: P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). CONCLUSIONS: The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.

Low-dose-rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse.

OBJECTIVES: To report clinical outcomes of 125 I low-dose-rate prostate brachytherapy (LDR-PB) as monotherapy or combined with androgen-deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high-risk localised prostate cancer. PATIENTS AND METHODS: Analysis of clinical outcomes from a prospective cohort of patients treated with LDR-PB alone or combined treatment in a single institution. Men with a high risk of disease relapse were identified by the National Institute for Health and Care Excellence (NICE) criteria or by the National Comprehensive Cancer Network (NCCN) criteria. Relapse-free survival (RFS), overall survival (OS), prostate cancer-specific survival (PCSS), and metastases-free survival (MFS), were analysed together with patient-reported symptom scores and physician-reported adverse events. RESULTS: The NICE and NCCN criteria identified 267 and 202 high-risk patients, respectively. NICE-defined patients had significantly lower pre-treatment PSA levels, Gleason scores <7, and a greater proportion of patients who received LDR-PB monotherapy. At 9 years after implantation RFS was 89% and 87% in the NICE and NCCN groups, respectively (log-rank P = 0.637), and OS 93% and 94%, respectively (log-rank P = 0.481). All of the survival estimates were similar between LDR-PB monotherapy and combined therapies. Cox proportional hazards regression confirmed RFS was similar between the treatment types. Treatment-related toxicity was also similar between the treatment methods. CONCLUSION: LDR-PB is effective at controlling localised prostate cancer in patients with a high risk of disease relapse. As the present study was not randomised, it is not possible to define those patients who need the addition of ADT and/or EBRT. However, the NICE criteria appear suitable to define treatment options where patients could benefit from LDR-PB as monotherapy or combined treatment. This choice should be discussed with the patient taking into account comorbidities and presence of multiple high-risk factors.

Long-term oncological outcomes and toxicity in 597 men aged ≤60 years at time of low-dose-rate brachytherapy for localised prostate cancer.

OBJECTIVES: To report oncological and functional outcomes of men treated with low-dose-rate (LDR) prostate brachytherapy aged ≤60 years at time of treatment. PATIENTS AND METHODS: Of 3262 patients treated with LDR brachytherapy at our centre up to June 2016, we retrospectively identified 597 patients aged ≤60 years at treatment with ≥3-years post-implantation follow-up and four prostate-specific antigen (PSA) measurements, of which one was at baseline. Overall survival (OS), prostate cancer-specific survival (PCSS) and relapse free survival (RFS) were analysed together with prospectively collected physician-reported adverse events and patient-reported symptom scores. RESULTS: The median (range) age was 57 (44-60) years, follow-up was 8.9 (1.5-17.2) years, and PSA follow-up 5.9 (0.8-15) years. Low-, intermediate- and high-risk disease represented 53%, 37% and 10% of the patients, respectively. At 10 years after implantation OS and PCSS were 98% and 99% for low-risk, 99% and 100% for intermediate-risk, and 93% and 95% for high-risk disease, respectively. At 10 years after implantation RFS, using the PSA level nadir plus 2 ng/mL definition, was 95%, 90% and 87% for low-, intermediate-, and high-risk disease, respectively. Urinary stricture was the most common genitourinary adverse event occurring in 19 patients (3.2%). At 5 years after implantation erectile function was preserved in 75% of the patients who were potent before treatment. CONCLUSION: LDR brachytherapy is an effective treatment with long-term control of prostate cancer in men aged ≤60 years at time of treatment. It was associated with low rates of treatment-related toxicity and can be considered a first-line treatment for prostate cancer in this patient group.

Modified transurethral resection of the prostate (TURP) for men with moderate lower urinary tract symptoms (LUTS) before brachytherapy is safe and feasible.

OBJECTIVE: To report the urinary toxicity outcomes for patients at greater risk of voiding symptoms and retention who received a modified limited transurethral resection of the prostate (TURP) before low-dose rate (LDR) brachytherapy. PATIENTS AND METHOD: Data were analysed from patients receiving the above procedures between 2006 to present, taken from the prospective brachytherapy database of 2000 patients at the St. Luke's Cancer Centre. The limited TURP (TURP(BXT) ) was performed at a median (range) of 64 (25-205) days before seed implantation with a median resection weight of 1.15 g. Selection criteria were based on patients with moderate lower urinary tract symptoms, poor flow or post-void residual urine volume (PVR), or a prominent middle lobe or high bladder neck on transrectal ultrasonography. Baseline prostate cancer characteristics, uroflowmetry, International Prostate Symptom Score (IPSS) and quality-of-life QoL scores were collected and compared with follow-up IPSS and QoL scores. RESULTS: Data for 112 patients was gathered from the database. The TURP(BXT) resulted in statistically significant improvements before LDR brachytherapy in maximum urinary flow rate (Qmax ) and PVR, IPSS and QoL scores (the mean Qmax before vs after the TURP(BXT) was 11.3 vs 16.7 mL/s). The IPSS and QoL scores at 6 months after seed implantation were increased compared with baseline values before the TURP(BXT) (mean IPSS at 6 months 11.7 vs 9.2 before TURP(BXT) ), but no difference at 1 year (mean IPSS 9), and improved scores at 2, 3, 4 and 5 years follow-up (mean IPSS of 7.9, 5.6, 5.3 and 7.4, respectively). CONCLUSION: The present study suggests patients at increased risk of deteriorating voiding symptoms, including urinary retention, are no longer contraindicated against LDR brachytherapy if they receive a modified TURP before seed implantation. This procedure does not appear to carry the risk of urinary incontinence thought to be associated with a conventional TURP before LDR brachytherapy.

Importance of HOX genes in normal prostate gland formation, prostate cancer development and its early detection.

The aims of this paper were to review the published literature on the role of HOX genes in the development of the normal prostate gland and in prostate cancer and to discuss the potential role of the HOX family member, Engrailed-2 (EN2), as a diagnostic test of PCa. Hox genes were first described in the fruit fly Drosphila melanogaster, where they specify the body plan and control the formation of body segments. They belong to a family of homeodomain-containing transcription factors that determine cell and tissue identity during normal embryonic development. They have been shown to be re-expressed by several different types of cancers. Studies have shown that different Hox genes are responsible for the development of the separate lobes of the prostate gland, the seminal vesicles and the epididymis. All HOX13 paralogues are expressed in the adult human prostate, suggesting the possibility of similarities between the function and expression of HOX genes within urological structures at similar anterior-posterior positions. The oncogenic and tumour suppressor signalling pathways associated with PCa converge on the HOX gene network, which ultimately controls gene expression, affecting tumour formation and metastatic progression. The Engrailed genes (EN1 and EN2) from the HOX gene family show a very high degree of functional conservation during embryonic development. Urinary EN2 is being investigated as a potential diagnostic marker of early PCa. It is secreted into the urine by PCa cells but not by normal prostatic tissue. A recent study has shown an association between urinary EN2 levels and cancer volume in radical prostatectomy specimens. The ability to predict tumour volume could inform the treatment decision-making process for patients with localized PCa choosing between active surveillance and radical treatment options.

Correlation between prostate brachytherapy-related urethral stricture and peri-apical urethral dosimetry: a matched case-control study.

BACKGROUND AND PURPOSE: Radiation dose to the bulbomembranous urethra has been shown to correlate with urethral stricture formation. This retrospective case-control study was designed to explore the relationship between dose to the apical/peri-apical regions of the urethra and development of brachytherapy (BXT)-related urethral stricture. MATERIALS AND METHODS: Cases were patients who developed urethral stricture after treatment with BXT as monotherapy and who had urethral dosimetry post-implant. Each case was matched with a control that had not developed urethral stricture. Dosimetry was compared between cases and controls. RESULTS: Twenty-three cases were pair matched with 23 controls. There were no significant differences between the two groups in terms of age, presenting Prostate Specific Antigen (PSA), International Prostate Symptom Score (IPSS) or Gleason score. The dose delivered to the peri-apical and apical urethra was significantly higher for cases when compared with controls (peri-apical urethra: mean V(150) 1.1 Vs 0.8 cc [p=0.02]; apical urethra: mean dose 200 Vs 174 Gy [p=0.01]). The distance from the prostate apex to isodose lines was also found to be significant in predicting stricture formation. CONCLUSION: There was evidence to suggest that the development of BXT-related stricture was associated with radiation dose at the apical and peri-apical urethra. Attention to the dose delivered to those areas may minimise the risk of developing such morbidity.

4D Brachytherapy, a novel real-time prostate brachytherapy technique using stranded and loose seeds.

What's known on the subject? and What does the study add? There are a number of techniques used successfully to perform brachytherapy, including 2-stage procedures and realtime techniques using loose seeds. This study demonstrates a one-stage realtime brachytherapy technique using stranded seeds with improved time efficiency and clinical outcome: 4D Brachytherapy. This paper reviews the development of a new one-stage prostate brachytherapy technique (4D Brachytherapy) using a combination of stranded and loose seeds. This novel technique utilizes a nomogram constructed from over 1000 procedures to calculate the seed requirement in advance of the implant. This allows stranded seeds to be pre-ordered and loaded prior to the procedure rather than per-operatively, resulting in a more efficient use of operating room time. The use of both stranded and loose seeds may reduce the risk of migration from peripherally placed seeds via the venous plexus, whilst maintaining the flexibility to optimize the dose within the prostate and especially at the apex of the gland. Prospectively collected data show significantly improved dosimetry: median D(90) 143 and 153 Gy (P < 0.005) and median V(100) 88% and 93% (P < 0.005) for the Seattle technique and 4D Brachytherapy implant technique, respectively. Also there was a reduced short-term urinary morbidity as assessed by the change in International Prostate Symptom Score (IPSS) at 3 months and 1 year compared with the Seattle technique. Mean (sd) change in IPSS from baseline at 1 year was 2.73 (5.92) and 0.97 (5.10) for the Seattle and 4D Brachytherapy series, respectively (P < 0.049).

A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy.

UNLABELLED: Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Men with prostate cancer have higher rates of non-cancer mortality and CV morbidity and some of that excess risk has been attributed to the treatment they receive. ADT is an established treatment option for men with locally-advanced and metastatic prostate cancer and, although it has been shown to confer a disease-free survival advantage, it has also been associated with an increased incidence of CV disease and the metabolic syndrome (characterized by a cluster of CV risk factors, including insulin resistance). The benefits of the insulin sensitizer metformin and lifestyle intervention for reducing the incidence of metabolic syndrome have been shown in patients with impaired glucose tolerance. At the time of writing, the present study is the first to use metformin and lifestyle intervention in men with prostate cancer with the aim of reducing the risk of developing ADT-related CV morbidity and the metabolic syndrome. The study shows that lifestyle changes and metformin may indeed reduce the complications of androgen suppression in these men. Although further investigations are needed to establish which of the two interventions may be most beneficial, the favourable effects of a combination of these interventions on patients' quality of life and the potential for improved overall survival are of clinical significance. OBJECTIVE: To investigate the effects of metformin and lifestyle changes on the development of androgen deprivation therapy (ADT)-related metabolic syndrome. PATIENTS AND METHODS: Men with prostate cancer due to receive ADT were recruited and randomized. Controls received ADT alone. Men in the intervention arm received ADT with 6 months of metformin, a low glycaemic index diet and an exercise programme. All patients were investigated pretreatment and at 6 months for the metabolic syndrome, as well as for related biochemical and physical parameters. RESULTS: In total, 40 men were recruited and randomized (20 to each arm). After 6 months, significant improvements in abdominal girth (P= 0.05), weight (P < 0.001), body mass index (P < 0.001) and systolic blood pressure (P= 0.01) were seen in the intervention arm compared to controls. Biochemical markers of insulin resistance did not differ significantly. CONCLUSIONS: The present study shows the potential benefits of metformin and lifestyle changes in ADT-treated men. Further studies will aim to determine which intervention is most important, and may show that overall survival can be improved.

Long-term toxicity and quality of life up to 10 years after low-dose rate brachytherapy for prostate cancer.

OBJECTIVE: To report on the long-term toxicity outcome for patients with prostate cancer treated by low-dose rate (LDR) brachytherapy (BXT). PATIENTS AND METHODS: The study population comprised a cohort of men treated in our centre between March 1999 and April 2004 with LDR BXT for prostate cancer who had at least 5 years of follow-up post-implant. Patients who had died or experienced biochemical failure were excluded. We contacted eligible patients and asked them to complete a questionnaire to assess current urinary, erectile and bowel function. Urinary and erectile function was compared pre- and post-treatment and outcomes were assessed by treatment modality. RESULTS: Of the 226 LDR BXT-treated patients with >5 years of follow-up, 174 (77.0%) responded to the questionnaire. The mean International Prostate Symptom Score (IPSS) increased from 6.70 pre-BXT to 7.91 at follow-up (P = 0.003). Of the patients with mild symptoms pre-BXT (IPSS, 0-7), 64.2% retained mild symptoms at follow-up, 31.2% developed moderate symptoms (IPSS, 8-9) and 4.6% reported severe symptoms (IPSS, 20-35). A good or acceptable quality of life (QoL) secondary to urinary symptoms (IPSS QoL, 0-4) was reported by 98.0% of respondents. Of those patients potent (International Index of Erectile Function-5 ≥11) pre-BXT, 62.9% remained potent at follow-up. There were no differences in the proportion of patients who were potent when analyzed by the number of years post-implant. At follow-up, 51.7% and 45.4% of patients, respectively, had normal or mild bowel symptoms as indicated by the European Organisation for the Research and Treatment of Cancer questionnaire (QLQ-C30/PR25 scores, 4-8). Moderate bowel symptoms (QLQ-C30/PR25 scores, 9-12) were reported by 2.9% of respondents; none reported severe symptoms. CONCLUSION: The present study shows low morbidity after LDR BXT over the long-term for a large cohort of patients.

The role of transperineal template prostate biopsies in restaging men with prostate cancer managed by active surveillance.

OBJECTIVE: To evaluate the role of transperineal template prostate biopsies in men on active surveillance. PATIENTS AND METHODS: In all, 101 men on active surveillance for prostate cancer underwent restaging transperineal template prostate biopsies at a single centre. Criteria for active surveillance were ≤75 years, Gleason ≤3+3, prostate-specific antigen (PSA) ≤15 ng/mL, clinical stage T1-2a and ≤50% ultrasound-guided transrectal biopsy cores positive for cancer with ≤10 mm of disease in a single core. The number of men with an increase in disease volume or Gleason grade on transperineal template biopsy and the number of men who later underwent radical treatment were assessed. The role of PSA and PSA kinetics were studied. RESULTS: In all, 34% of men had more significant prostate cancer on restaging transperineal template biopsies compared with their transrectal biopsies. Of these men, 44% had disease predominantly in the anterior part of the gland, an area often under-sampled by transrectal biopsies. In the group of men who had their restaging transperineal template biopsies within 6 months of commencing active surveillance 38% had more significant disease. There was no correlation with PSA velocity or PSA doubling time. In total, 33% of men stopped active surveillance and had radical treatment. CONCLUSIONS: Around one-third of men had more significant prostate cancer on transperineal template biopsies. This probably reflects under-sampling by initial transrectal biopsies rather than disease progression.

A randomized controlled trial investigating the effects of celecoxib in patients with localized prostate cancer.

UNLABELLED: Cyclooxygenase-2 (COX-2) is associated with tumour promotion, inhibition of apoptosis, angiogenesis and metastasis. Celecoxib, a selective COX-2 inhibitor was investigated, in patients with clinically localized prostate cancer using immunohistochemistry. PATIENTS AND METHODS: Patients with cT1-2 prostate cancer (n=45) were randomized to celecoxib 400mg b.d. or no treatment for four weeks prior to radical prostatectomy. Histological sections of preoperative biopsy and matched radical prostatectomy specimens were stained for markers of cell proliferation (MIB-1/Ki-67), microvessel density (CD-31 with Weidner scoring), COX-2, apoptosis (TUNEL analysis), angiogenic factors (VEGF and KDR) and HIF-1. RESULTS: Celecoxib decreased tumour cell proliferation, microvessel density, angiogenesis and HIF-1 whilst enhancing apoptosis. These effects approached statistical significance in a multivariate model and the cell proliferation index approached statistical significance on univariate analysis. CONCLUSION: In this pilot study a 4 week regimen of celecoxib resulted in measurable biological effects in prostate cancer tissue. These findings warrant further investigation.

Novel prostate brachytherapy technique: improved dosimetric and clinical outcome.

PURPOSE: Erectile dysfunction following prostate brachytherapy is reported to be related to dose received by the penile bulb. To minimise this, whilst preserving prostate dosimetry, we have developed a technique for I-125 seed brachytherapy using both stranded seeds and loose seeds delivered with a Mick applicator, and implanted via the sagittal plane on trans-rectal ultrasound. MATERIALS AND METHODS: Post-implant dosimetry and potency rates were compared in 120 potent patients. In Group 1, 60 patients were treated using a conventional technique of seeds implanted in a modified-uniform distribution. From January 2005, a novel technique was developed using stranded seeds peripherally and centrally distributed loose seeds implanted via a Mick applicator (Group 2). The latter technique allows greater flexibility when implanting the seeds at the apex. Each patient was prescribed a minimum peripheral dose of 145 Gy. No patients received external beam radiotherapy or hormone treatment. There was no significant difference in age or pre-implant potency score (mean IIEF-5 score 22.4 vs. 22.6, p=0.074) between the two groups. RESULTS: The new technique delivers lower penile bulb doses (D(25) as %mPD - Group 1: 61.2+/-35.7, Group 2: 29.7+/-16.0, p<0.0001; D(50) as %mPD - Group 1: 45.8+/-26.9, Group 2: 21.4+/-11.7, p<0.0001) whilst improving prostate dosimetry (D(90) - Group 1: 147 Gy+/-21.1, Group 2: 155 Gy+/-16.7, p=0.03). At 2 years, the potency rate was also improved: Group 1: 61.7%; Group 2: 83.3% (p=0.008). CONCLUSIONS: In this study, the novel brachytherapy technique using both peripheral stranded seeds and central loose seeds delivered via a Mick applicator results in a lower penile bulb dose whilst improving prostate dosimetry, and may achieve higher potency rates.

Venous thromboembolism and cyproterone acetate in men with prostate cancer: a study using the General Practice Research Database.

OBJECTIVE: To evaluate the risk of venous thromboembolism (VTE) associated with the use of cyproterone acetate (CPA) amongst men with prostate cancer. PATIENTS AND METHODS: Using data from the General Practice Research Database, cases of VTE were identified amongst men with prostate cancer. Four controls with no evidence of a VTE were selected for each case. The time from diagnosis of prostate cancer to first hormonal treatment, and from first hormonal treatment to VTE, was compared for different treatments. Adjusted risk estimates for VTE were derived from further analysis using a nested case-control study design amongst all men with advanced prostate cancer, qualified by evidence of hormonal treatment. RESULTS: The time between diagnosis and first treatment was significantly shorter for men first treated with CPA than for men first treated with a luteinizing hormone releasing hormone (LHRH) analogue (adjusted hazard ratio 1.33, 95% confidence interval, CI, 1.06-1.67). When the first treatment was CPA, the treatment-free period after diagnosis was significantly shorter for men who later had a VTE than for those who did not. The case-control study yielded an adjusted risk estimate for VTE amongst CPA users that was significantly higher than amongst men who were prescribed an LHRH analogue or who had had an orchidectomy (adjusted odds ratio 5.23, 95% CI 3.12-8.79). CONCLUSION: There was a greater risk of VTE associated with CPA, which might be due to differences in disease severity between users of different products. The clinical significance of this finding is unclear.

Are prostatic biopsies necessary in men aged > or =80 years?

OBJECTIVE: To examine whether prostatic biopsies are necessary in all men aged > or =80 years, as men found to have prostate cancer are frequently treated with a 'watch and wait' policy or with hormonal withdrawal alone, and biopsies are associated with a small but significant complication rate. PATIENTS AND METHODS: The findings on a digital rectal examination (DRE), the prostate-specific antigen (PSA) level, the biopsy and staging bone scan results for all men aged > or = 80 years who had prostatic biopsies over a 3-year period were reviewed, together with those in a group of men aged <80 years for comparison. All biopsy samples had been examined in one of three histopathology units, and 33 consultant urological surgeons contributed. RESULTS: In all, 210 biopsies from 205 men aged > or = 80 years were identified, of whom 163 (79%) had biopsy-confirmed prostate cancer. All 29 men with a PSA level of > or = 100 ng/mL, 98% of 47 with > or = 50 ng/mL, 97% of 76 with > or = 30 ng/mL and 92% of 101 with > or = 20 ng/mL had biopsy cores containing cancer; 63% of men with a PSA level of <20 ng/mL had cancer on biopsy. In men with cancer and a PSA level of > or = 30 ng/mL, 92% had Gleason grade > or = 7 and 93% were treated with hormonal withdrawal alone. In all men with cancer the DRE was abnormal in 91%, the mean number of positive cores was 59% and the bone scan was positive in 18%. The DRE was abnormal in 77% of men with benign biopsies. CONCLUSIONS: In men aged > or = 80 years with a PSA level of > or = 30 ng/mL, at least 97% had prostate cancer, >90% of whom had high-grade disease, and nearly all with cancer received active pharmacological treatment. In the vast majority of these men prostate biopsies did not alter their cancer management. The value of prostatic biopsy in this age group, with a PSA level of > or = 30 ng/mL, is questionable.

Extensive transperineal template biopsies of prostate: modified technique and results.

OBJECTIVES: To describe the modified technique and results of extensive transperineal template prostate biopsies in men with a high risk of prostate cancer in whom repeated transrectal biopsies are not diagnostic. METHODS: Men who had a rising prostate-specific antigen (PSA) level and had at least two sets of benign octant biopsies or two or more prior biopsies containing high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation were included. A biplanar transrectal ultrasound probe was attached to a brachytherapy stepping unit and a standard 0.5-cm brachytherapy template was positioned over the perineum. In the transverse image, the prostate was divided into right and left and anterior, middle, and posterior regions, and three to five transperineal biopsy cores were taken in each of the six regions through the template. RESULTS: Sixty men underwent extensive transperineal template biopsies. Their mean age was 64 years (SD 6.4), the median PSA level was 12.9 ng/mL (range 4.6 to 35.7), and the median prostate volume was 54 cm3 (range 34 to 199). Cancer was detected in 23 men (38%), of whom 17 (74%) had Gleason grade 6, 5 (21%) Gleason grade 7, and 1 (4%) Gleason grade 9 disease. Cancer was identified in the anterior region of the prostate alone in 12 men (60%). One man required overnight admission for hematuria and two developed urinary retention; no cases of sepsis developed. CONCLUSIONS: In men with a clinical suspicion of prostate cancer, but benign or equivocal prostate biopsies, extensive transperineal template biopsy of the prostate is a useful diagnostic tool. It allows sampling of the whole prostate in a systematic and safe fashion.

Biochemical (prostate-specific antigen) relapse-free survival and toxicity after 125I low-dose-rate prostate brachytherapy.

OBJECTIVE: To report our clinical experience and 5-year prostate-specific antigen (PSA) relapse-free survival rate for early-stage prostate cancer after (125)I low-dose-rate prostate brachytherapy. PATIENTS AND METHODS: In all, 300 patients were treated between March 1999 and April 2003, and followed prospectively. Patients were stratified into low-, intermediate- and high-risk groups, and those receiving neoadjuvant androgen deprivation (NAAD) or not. Kaplan-Meier estimates of PSA relapse-free survival and PSA nadirs were obtained for all patients and for the risk groups. Toxicity, as urinary and erectile dysfunction (ED), were reported from a prospective database. RESULTS: The median (range) follow-up was 45 (33-82) months. The actuarial PSA relapse-free survival was 93% at 5 years; 21 (7%) of patients had evidence of biochemical failure as defined by the American Society of Therapeutic Radiation Oncology criteria. There was no significant difference in actuarial survival for patients in the different risk groups, or between those receiving NAAD or not (low-risk 96%, intermediate 89%, high 93%, P = 0.12; NAAD 92%, no NAAD 95%, P = 0.30). Overall the 3-year median PSA level was 0.3 ng/mL (192 men). There was no significant difference in median 3-year PSA levels for different risk groups, or for those treated with or with no NAAD. The 3- and 4-year PSA nadir of <0.5 ng/mL was achieved by 71% and 86% of men, respectively. The acute urinary retention rate was 7%; 5.6% of men developed urethral strictures requiring dilatation, while 2.7% required a transurethral resection of the prostate after implantation, for obstructive symptoms. Of patients with no ED before treatment, 62% had no ED at 2 years, and of these 60% used a phosphodiesterase inhibitor. CONCLUSION: This prospective series confirms the excellent overall biochemical survival after (125)I brachytherapy; the treatment was tolerated well, with early and late urinary toxicity and ED similar to other published results.