Trimodality Therapy With Iodine-125 Brachytherapy, External Beam Radiation Therapy, and Short- or Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer: Results of a Multicenter, Randomized Phase 3 Trial (TRIP/TRIGU0907).

PURPOSE: This phase 3 randomized investigation was designed to determine whether 30 months of androgen deprivation therapy (ADT) was superior to 6 months of ADT when combined with brachytherapy and external beam radiation therapy (EBRT) for localized high-risk prostate cancer. METHODS AND MATERIALS: This study was conducted at 37 hospitals on men aged 40 to 79 years, with stage T2c-3a, prostate-specific antigen >20 ng/mL, or Gleason score >7, who received 6 months of ADT combined with iodine-125 brachytherapy followed by EBRT. After stratification, patients were randomly assigned to either no further treatment (short arm) or 24 months of adjuvant ADT (long arm). According to the Phoenix definition of failure, the primary endpoint was the cumulative incidence of biochemical progression. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific mortality, overall survival, and grade 3+ adverse events. An intention-to-treat analysis was conducted using survival estimates determined using competing risk analyses. RESULTS: Of 332 patients, 165 and 167 were randomly assigned to the short and long arms, respectively. The median follow-up period was 9.2 years. The cumulative incidence of biochemical progression at 7 years was 9.0% (95% CI, 5.5-14.5) and 8.0% (4.7-13.5) in the short and long arms, respectively (P = .65). The outcomes of secondary endpoints did not differ significantly between the arms. Incidence rates of endocrine- and radiation-related grade 3+ adverse events for the short versus long arms were 0.6 versus 1.8% (P = .62) and 1.2 versus 0.6% (P = .62), respectively. CONCLUSIONS: Both treatment arms showed similar efficacy among selected populations with high-risk features. The toxicity of the trimodal therapy was acceptable. The present investigation, designed as a superiority trial, failed to demonstrate that 30-month ADT yielded better biochemical control than 6-month ADT when combined with brachytherapy and EBRT. Therefore, a noninferiority study is warranted to obtain further evidence supporting these preliminary results.

Biochemical outcomes and toxicities in young men with prostate cancer after permanent iodine-125 seed implantation: Prospective cohort study in 6662 patients.

PURPOSE: We evaluated the effect of age, <60 and ≥60 years, on biochemical outcomes and toxicities in patients with prostate cancer who underwent permanent seed implantation (PI) ± external beam radiation therapy ± hormone therapy in a national Japanese prospective cohort study (J-POPS). METHODS AND MATERIALS: The safety and efficacy analyses included 6721 and 6662 patients, respectively. We categorized patients into two age groups: <60 (n = 716) and ≥60 (n = 6,005) years. We used propensity score matching (PSM) to estimate the marginal effect of age on biochemical freedom from failure (bFFF) using a Phoenix definition and Cox proportional hazard models. RESULTS: The median followup period was 60.0 months. Without PSM, men <60 years demonstrated similar 5-year bFFF (96.3%) compared with men ≥60 years (95.6%; p = 0.576); percent positive biopsies, biologically effective dose, Gleason score, risk classification, and supplemental external beam radiation therapy (p <0.001, <0.001, <0.001, 0.008, and <0.001) were significantly associated with bFFF while age was not (p = 0.576). With PSM, bFFF was not significantly different between age groups (p = 0.664); however, men <60 years showed a significantly lower incidence of declining erectile function, grade ≥2 all urinary toxicities, urinary frequency/urgency, and rectal bleeding (p <0.001, 0.024, 0.031, and 0.010) than men ≥60 years. CONCLUSIONS: After PI, men <60 years achieved a comparable 5-year biochemical control rate and showed a lower incidence of several toxicities compared to men ≥60 years. This suggests that PI should be an excellent treatment option for men <60 years with prostate cancer.

Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score-matched analysis.

PURPOSE: The purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer. METHODS AND MATERIALS: Overall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan-Meier curves, and predictors were identified using Cox proportional hazards regression models. RESULTS: After propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58-4.03) and ADT use (HR: 0.55, 95% CI: 0.34-0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16-0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08-1.16) and comorbidities (HR: 1.56, 95% CI: 1.04-2.34) were associated with all-cause mortality. CONCLUSIONS: A risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.

Selection of patients who would not require long-term prostate-specific antigen monitoring after low-dose-rate brachytherapy.

PURPOSE: To identify patients at extremely low risk of biochemical recurrence (BCR) of prostate cancer after low-dose-rate brachytherapy (LDR-BT) to determine when prostate-specific antigen (PSA) monitoring can be stopped. METHODS AND MATERIALS: We retrospectively reviewed clinicopathologic data of patients with prostate cancer who underwent LDR-BT between 2003 and 2011. Of 1569 patients reviewed, 689 (43.9%) received combination external beam radiotherapy, and 970 (61.8%) had neoadjuvant hormonal therapy. We stratified patients according to risk factors identified by multivariate analysis and assessed the factors for an association with BCR (defined as ≥2 ng/mL higher than the nadir). RESULTS: The median followup was 96 months. Of 1531 patients who were BCR-free at 3 years after treatment, 76 subsequently developed BCR; of 1500 who were BCR-free at 5 years, 45 eventually had BCR. On multivariate analysis, independent risk factors for BCR were the National Comprehensive Cancer Network risk group at diagnosis and PSA levels at 3 or 5 years after radiotherapy. In the low-risk group, no patient with a PSA level ≤0.2 ng/mL at 3 years after radiotherapy subsequently developed BCR. In the intermediate-risk group, no patients with a PSA level ≤0.2 ng/mL at 5 years subsequently developed BCR. CONCLUSIONS: The National Comprehensive Cancer Network risk group at diagnosis and PSA values at 3 and 5 years after LDR-BT are independently associated with a risk of later BCR. Using these two factors may help to select patients for whom PSA monitoring could be stopped because they have an extremely low risk of later BCR.

Predictive factors of long-term rectal toxicity following permanent iodine-125 prostate brachytherapy with or without supplemental external beam radiation therapy in 2216 patients.

PURPOSE: We analyzed factors associated with rectal toxicity after iodine-125 prostate brachytherapy (BT) with or without external beam radiation therapy (EBRT). METHODS AND MATERIALS: In total, 2216 prostate cancer patients underwent iodine-125 BT with or without EBRT between 2003 and 2013. The median followup was 6.9 years. Cox proportional hazards modeling was used for univariate and multivariate analyses to assess clinical and dosimetric factors associated with rectal toxicity. Dosimetric parameters from 1 day after implantation (Day 1) and 1 month after implantation (Day 30) were included in the analyses. RESULTS: The 7-year cumulative incidence of Grade 2 or higher rectal toxicity was 5.7% in all patients. The multivariate analysis revealed that antiplatelet or anticoagulant therapy, neoadjuvant androgen deprivation therapy, treatment modality, Day 1 rectal volume receiving 100% of the prescribed dose (RV100), and the Day 30 minimal percent of the prescribed dose delivered to 30% of the rectum (RD30) were associated with rectal toxicity. Day 1 RV100 was a common predictor in both BT-alone and the BT + EBRT groups. The 5-year cumulative incidence of Grade 2 or higher rectal toxicity was 12.6%, 5.9%, and 1.7% for BT + 3-dimensional conformal radiation therapy, BT + intensity-modulated radiation therapy, and the BT-alone groups, respectively (p < 0.001). CONCLUSIONS: Rectal dosimetric parameters in BT were associated with late rectal toxicity. Although the risk of rectal toxicity was higher when EBRT was combined with BT, with proper and achievable rectal dose constraints intensity-modulated radiation therapy yielded less toxicity than 3-dimensional conformal radiation therapy.

Predictive factors for urinary toxicity after iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy.

PURPOSE: We examined the factors associated with urinary toxicities because of brachytherapy with iodine-125 with or without supplemental external beam radiotherapy (EBRT) for prostate cancer. METHODS AND MATERIALS: We investigated 1313 patients with localized prostate cancer treated with iodine-125 brachytherapy with or without supplemental EBRT between 2003 and 2009. The International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events data were prospectively determined. Patients, treatment, and implant factors were investigated for their association with urinary toxicity or symptoms. RESULTS: IPSS resolution was not associated with biologically effective dose (BED). Baseline IPSS, total needles, and the minimal dose received by 30% of the urethra had the greatest effect according to multivariate analysis (MVA). Urinary symptom flare was associated with baseline IPSS, age, BED, and EBRT on MVA. Urinary symptom flare and urinary Grade 2 or higher (G2+) toxicity occurred in 51%, 58%, and 67% (p = 0.025) and 16%, 22%, and 20% (p = 0.497) of the <180, 180-220, and >220 Gy BED groups, respectively. Urinary G2+ toxicity was associated with baseline IPSS, neoadjuvant androgen deprivation therapy (NADT), and seed density on MVA. When we divided patients into four groups according to prostate volume (<30 cc or ≥30 cc) and NADT use, urinary G2+ toxicity was most commonly observed in those patients with larger prostates who received NADT, and least in the patients with smaller prostates and no NADT. CONCLUSIONS: NADT was associated with urinary G2+ toxicity. Higher dose and supplemental EBRT did not appear to increase moderate to severe urinary toxicities or time to IPSS resolution; however, it influenced urinary symptom flare.

Permanent prostate brachytherapy with or without supplemental external beam radiotherapy as practiced in Japan: outcomes of 1300 patients.

PURPOSE: To report outcomes for men treated with iodine-125 ((125)I) prostate brachytherapy (BT) at a single institution in Japan. METHODS AND MATERIALS: Between 2003 and 2009, 1313 patients (median age, 68 years) with clinically localized prostate cancer were treated with (125)I BT. Median prostate-specific antigen level was 7.6 ng/mL (range, 1.1-43.3). T-stage was T1c in 60%, T2 in 39%, and T3 in 1% of patients. The Gleason score was <7, 7, and >7 in 49%, 45%, and 6% of patients, respectively. Neoadjuvant androgen deprivation therapy was used in 40% of patients and combined external beam radiotherapy of 45 Gy in 48% of patients. Postimplant dosimetry was performed after 30 days after implantation, with total doses converted to the biologically effective dose. Survival functions were calculated by the Kaplan-Meier method and Cox hazard model. RESULTS: Median followup was 67 months (range, 6-126). The 7-year biochemical freedom from failure for low-, intermediate-, and selected high-risk prostate cancers were 98%, 93%, and 81%, respectively (p < 0.001). Multivariate analysis identified the Gleason score, initial prostate-specific antigen level, positive biopsy rate, dose, and neoadjuvant androgen deprivation therapy as predictors for biochemical freedom from failure. The 7-year actuarial developing Grade 3+ genitourinary and gastrointestinal toxicity was 2% and 0.3%, respectively. Forty-four percent patients with normal baseline potency retained normal erectile function at 5 years. CONCLUSIONS: (125)I prostate BT is a highly effective treatment option for low-, intermediate-, and selected high-risk prostate cancers. Side effects were tolerable. An adequate dose may be required to achieve successful biochemical control.

A dose-response analysis of biochemical control outcomes after (125)I monotherapy for patients with favorable-risk prostate cancer.

PURPOSE: To define the optimal dose for (125)I prostate implants by correlating postimplantation dosimetry findings with biochemical failure and toxicity. METHODS AND MATERIALS: Between 2003 and 2009, 683 patients with prostate cancer were treated with (125)I prostate brachytherapy without supplemental external beam radiation therapy and were followed up for a median time of 80 months. Implant dose was defined as the D90 (the minimal dose received by 90% of the prostate) on postoperative day 1 and 1 month after implantation. Therefore, 2 dosimetric variables (day 1 D90 and day 30 D90) were analyzed for each patient. We investigated the dose effects on biochemical control and toxicity. RESULTS: The 7-year biochemical failure-free survival (BFFS) rate for the group overall was 96.4% according to the Phoenix definition. A multivariate analysis found day 1 D90 and day 30 D90 to be the most significant factors affecting BFFS. The cutoff points for day 1 D90 and day 30 D90, calculated from ROC curves, were 163 Gy and 175 Gy, respectively. By use of univariate analysis, various dosimetric cutoff points for day 30 D90 were tested. We found that day 30 D90 cutoff points from 130 to 180 Gy appeared to be good for the entire cohort. Greater D90s were associated with an increase in late genitourinary or gastrointestinal toxicity ≥ grade 2, but the increase was not statistically significant. CONCLUSIONS: Improvements in BFFS rates were seen with increasing D90 levels. Day 30 D90 doses of 130 to 180 Gy were found to serve as cutoff levels. For low-risk and low-tier intermediate-risk prostate cancer patients, high prostate D90s, even with doses exceeding 180 Gy, achieve better treatment results and are feasible.

Combined brachytherapy and external beam radiotherapy without adjuvant androgen deprivation therapy for high-risk prostate cancer.

BACKGROUND: To report the outcomes of patients treated with combined iodine-125 (I-125) brachytherapy and external beam radiotherapy (EBRT) for high-risk prostate cancer. METHODS: Between 2003 and 2009, I-125 permanent prostate brachytherapy plus EBRT was performed for 206 patients with high-risk prostate cancer. High-risk patients had prostate-specific antigen ≥ 20 ng/mL, and/or Gleason score ≥ 8, and/or Stage ≥ T3. One hundred and one patients (49.0%) received neoadjuvant androgen deprivation therapy (ADT) but none were given adjuvant ADT. Biochemical failure-free survival (BFFS) was determined using the Phoenix definition. RESULTS: The 5-year actuarial BFFS rate was 84.8%. The 5-year cause-specific survival and overall survival rates were 98.7% and 97.6%, respectively. There were 8 deaths (3.9%), of which 2 were due to prostate cancer. On multivariate analysis, positive biopsy core rates and the number of high-risk factors were independent predictors of BFFS. The 5-year BFFS rates for patients in the positive biopsy core rate <50% and ≥ 50% groups were 89.3% and 78.2%, respectively (p = 0.03). The 5-year BFFS rate for patients with the any single high-risk factor was 86.1%, compared with 73.6% for those with any 2 or all 3 high-risk factors (p = 0.03). Neoadjuvant ADT did not impact the 5-year BFFS. CONCLUSIONS: At a median follow-up of 60 months, high-risk prostate cancer patients undergoing combined I-125 brachytherapy and EBRT without adjuvant ADT have a high probability of achieving 5-year BFFS.

Five-year potency preservation after iodine-125 prostate brachytherapy.

BACKGROUND: We aimed to evaluate long-term erectile function following prostate brachytherapy, based on patient characteristics and treatment factors. METHODS: Between 2003 and 2006, 665 men with localized prostate cancer were treated with (125)I permanent seed implantation. None was given adjuvant hormone therapy. Erectile function was assessed before treatment, and at 6 months, 1, 2, 3, 4 and 5 years after implantation using the Mount Sinai Erectile Function Score (MSEFS) of 0-3 (0 = no erections, 1 = erections insufficient for intercourse, 2 = suboptimal erections but sufficient for intercourse, 3 = normal erectile function). Potency was defined as score 2 or 3, and 382 men were potent before treatment. Univariate and multivariate analyses were performed on the data from these 382 patients to identify variables associated with potency preservation. RESULTS: In patients who were potent before treatment, the actuarial potency preservation rate fell to 46.2 % at 6 months after brachytherapy, and then slowly recovered reaching 52.0 % at 5 years after brachytherapy. In multivariate logistic regression analysis, patient age (p = 0.04) and pre-treatment MSEFS (p < 0.001) were predictors of 5-year potency preservation. Neoadjuvant hormone therapy affected potency preservation only at 6 months after brachytherapy. CONCLUSIONS: Patient age at implantation and pre-treatment erectile function are predictive factors for the development of erectile dysfunction following prostate brachytherapy.

Outcomes following iodine-125 prostate brachytherapy with or without neoadjuvant androgen deprivation.

PURPOSE: To report the biochemical failure-free survival (BFFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with iodine-125 (I-125) brachytherapy for clinically localized prostate cancer. METHODS AND MATERIALS: Between 2003 and 2009, I-125 permanent prostate brachytherapy without supplemental external-beam radiotherapy was performed for 663 patients with low-risk and low-tier intermediate-risk (defined as organ-confined disease, PSA <10ng/mL, and Gleason score 3+4 with biopsy positive core rate <33%) prostate cancer. Early in the study period, the preplanning method was used in the first 104 patients, and later the real-time planning method was used. Biochemical failure was determined using the American Society for Therapeutic Radiology Oncology (ASTRO) and Phoenix definitions. RESULTS: The 7-year BFFS rates for the ASTRO and Phoenix definitions were 96.1% and 95.9%, respectively. The corresponding BFFS rates by risk group were 97.6% and 96.7% for low-risk, and 91.8% and 93.6% for low-tier intermediate-risk disease (p=0.007 and 0.08, respectively). The median times to biochemical failure in those who failed were 29.5 and 43.9months according to the ASTRO and Phoenix definitions, respectively. The 7-year CSS and OS were 99.1% and 96.4%. There was no significant difference in CSS or OS between the low-risk and low-tier intermediate-risk groups. In multivariate Cox regression analysis, risk group and prostate D90 were independent predictors of BFFS for the ASTRO definition, while only the prostate D90 was significant for the Phoenix definition. CONCLUSION: I-125 prostate brachytherapy results in excellent 7-year BFFS, CSS, and OS for low-risk and low-tier intermediate-risk prostate cancer.

Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial.

BACKGROUND: Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required. METHODS/DESIGN: This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 ((125)I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with (125)I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during (125)I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events. DISCUSSION: To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa. TRIAL REGISTRATION: UMIN000003992.

Dose constraint for minimizing grade 2 rectal bleeding following brachytherapy combined with external beam radiotherapy for localized prostate cancer: rectal dose-volume histogram analysis of 457 patients.

PURPOSE: To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram. METHODS AND MATERIALS: A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and for rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation. RESULTS: Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 ≤35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 ≤0.5 ml and a V30 ≤35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%. CONCLUSION: The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of development of Grade 2 rectal bleeding.

[Continuous bladder irrigation following transurethral resection of the prostate (TURP)].

PURPOSE: We investigated whether continuous bladder irrigation after Transurethral Resection of the Prostate (TURP) would prevent catheter obstruction by the clot. MATERIALS AND METHODS: We analyzed data from 761 patients registered in "a multi-institutional study of TURP clinical pathway" sponsored by the Ministry of Health, Labor and Welfare between 2001 and 2003. The difference of clinical backgrounds of the cases, resected weight, operating time, risk of being feverish, risk of catheter obstruction and chance of postoperative Transurethral Fulguration (TUF) between each institution were investigated. The risk factor of catheter obstruction is characterized and the significance of continuous bladder irrigation is discussed. RESULTS: The incidence of catheter obstruction in the four institutions, in which 90% or more of patients underwent continuous bladder irrigation, was significantly lower than that in the three institutions, in which continuous bladder irrigation was performed in selected patients whose hematuria was severe (4.4% VS 12.9%, p<0.001). There was no difference in the frequency of either pyrexia or postoperative TUF. Logistic regression analysis showed that significant factors for catheter obstruction are continuous bladder irrigation, resected tissue weight and preoperative urinary infection. CONCLUSIONS: Routine continuous bladder irrigation achieved a lower incidence of catheter obstruction. However, we recommend that urologists should decide whether to perform routine continuous irrigation, considering the frequency of catheter obstruction, safety, labor and cost.

[Evolution of common clinical path for transurethral resection of prostate (TURP)].

OBJECTIVES: Improvement of perioperative management for transurethral resection of the prostate (TURP) by revising the common clinical path was investigated in multiple hospitals. METHODS: We discussed perioperative outcomes using the common path in 2002 and revised it for 2003. Changes in perioperative outcomes between 2002 and 2003 and differences among hospitals were compared. RESULTS: There were no statistically significant differences in age, proportion of patients with mildly impaired activity of daily living and/or impaired cognition, general anesthesia, operating duration, resected weight, incidence of intraoperative complications and blood transfusion between 2002 and 2003. Although there were no differences in preoperative hospital stay, re-hospitalization rate and charges for surgery and anesthesia, Foley catheter was removed significantly earlier from postoperative day 2.9 to 2.3 and total medical charge significantly decreased from 43,703 to 39,661 units (1 unit = 10 yen). The incidence of postoperative pyrexia increased from 2.4% to 11.2% in 2003, however, the incidences of epididymitis, postoperative bleeding and postoperative difficulty on micturition remained stable. The average and standard deviation of postoperative hospital stay and total medical charge at each hospital decreased, however, differences among hospitals found in 2002 remained in 2003. CONCLUSION: We found that standardization can be accomplished by discussing perioperative management using a common path in multiple hospitals and revising the path as needed. Common clinical path should be a valid method of advancing standardization in Japan.

Rectal morbidity following I-125 prostate brachytherapy in relation to dosimetry.

BACKGROUND: To investigate rectal morbidity after I-125 prostate brachytherapy and to analyze predictive factors of rectal morbidity. METHODS: A group of 227 consecutive patients with localized prostate cancer were treated with I-125 prostate brachytherapy with or without external beam radiotherapy (EBRT) between September 2003 and January 2005. Rectal morbidity (diarrhea, bleeding and pain) was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Dosimetry was based on computerized tomography (CT) scan 1 month post-implant. The clinical, treatment-related and dosimetric factors were evaluated for the risk of grade 2 rectal morbidity. Rectal dosimetric factors included the rectal volume that received >100% and 150% of the prescribed dose, and the maximal rectal dose which was defined as the sum of the minimal dose received by 1% of the rectum volume and the prescribed dose of EBRT. RESULTS: Grade 2 rectal bleeding occurred in 10 (4.4%): for nine patients within the first year and for one patient between the first and second year. Grade 2 diarrhea occurred in one patient (0.4%) within the first year. No patient reported grade 2 pain. In the univariate analysis with grade 2 rectal bleeding, there were significant correlations with number of seeds, supplemental EBRT, and all of the rectal dosimetric parameters. On subsequent multivariate analysis, the only significant factor was the maximal rectal dose (P < 0.001). Rectal dose > 160 Gy was correlated to grade 2 rectal morbidity. All the patients with rectal dose > 160 Gy received EBRT. CONCLUSIONS: Manifestations of rectal morbidity are acceptable events after I-125 prostate brachytherapy. Rectal dose-volume histogram for the brachytherapy is a predictive method for assessing the risk of developing grade 2 rectal bleeding. Delivery of the rectal dose should not exceed 160 Gy in order to avoid rectal complications.

[Questionnaire survey of peri-operative management of transurethral prostate resection in Japan].

OBJECTIVES: We investigated perioperative management for transurethral resection of the prostate (TURP) in Japan. METHODS: The questionnaire survey was conducted in 1,213 educational institutions for urology. RESULTS: The questionnaires were returned from 722 (60%) institutions. Admission to hospital was most frequently scheduled on preoperative day 1; termination of continuous drip infusion, starting meal intake and walking on postoperative day 1; intravenous antibiotics for three days; removal of Foley catheter on postoperative day 4; oral antibiotics for 7 days; and discharge from hospital on postoperative day 7. CONCLUSION: Although hospitalization was 14 days or less at most institutions, several procedures, especially the administration of prophylactic antibiotics, were fairly varied. Discussions from various perspectives might be needed to standardize the perioperative management of TURP in Japan.

Serial changes of international prostate symptom score following I-125 prostate brachytherapy.

BACKGROUND: This study was conducted to assess serial changes in the International Prostate Symptom Score (IPSS) within the first 12 months after iodine-125 (I-125) prostate brachytherapy. METHODS: Between September 2003 and June 2004, a group of 103 patients with localized prostate cancer was treated with I-125 prostate brachytherapy, either alone (monotherapy; 60 patients) or in combination with external-beam radiotherapy (combined therapy; 43 patients). The IPSS was obtained at preimplant, and at 1, 6, and 12 months after treatment. The minimum IPSS follow-up for this study was 12 months. Dosimetry was based on computed tomography (CT) scan 1 month postimplant. Clinical, treatment-related, and dosimetric factors were assessed for correlations with the maximum IPSS increase (the peak IPSS minus the preimplant IPSS). RESULTS: The median preimplant IPSS was 7.0, with a median peak of 16 at 1 month. The IPSS returned to baseline in 42 patients (40.8%) and it returned to within 3 points of the baseline in 64 (62.1%) at 1-year follow-up. On univariate and multivariate analyses, the maximum IPSS increase was best predicted by lower preimplant IPSS, in both the monotherapy and combined therapy groups. CONCLUSION: In our series, IPSS after prostate brachytherapy peaked at 1 month and gradually returned to approximately baseline at 12 months.

[Brachytherapy for prostate cancer].

This review article aims to overview modern prostate brachytherapy in Japan. Permanent transperineal prostate brachytherapy with I-125 started in September, 2003 in Japan. Brachytherapy has several advantages: the dose is adapted precisely to the tumor shape and size, and the long-lived isotope gives a higher tumor dose with less damage to normal tissue; less-time consuming for patients and staff: long-term results comparable to surgery or external beam series in the USA; and quality of life after brachytherapy also appealing. These advantages have brought about increasing use in Japan as well. Patients with a high probability of organ-confined disease and a low-risk group are appropriately treated with brachytherapy. Brachytherapy candidates with a significant risk of extraprostatic extension should be treated with supplemental external beam radiation therapy. High-dose-rate (HDR) brachytherapy with Ir-192 has preceded seed implants in Japan. HDR has some theoretical advantages. Long-term results of brachytherapy in the USA are comparable with surgery or external beam irradiation so far. We should develop more sophisticated brachytherapy techniques in Japan.

[Implementation of a common clinical path for transurethral resection of prostate (TURP) in multiple hospitals].

PURPOSE: To investigate the length of hospitalization and medical charges when a common clinical path for TURP (transurethral resection of prostate) was implemented in multiple hospitals. PATIENTS AND METHODS: This study included 310 patients in 2001 and 298 in 2002, who were diagnosed with benign prostatic hyperplasia and who underwent TURP in seven hospitals in Japan. While the patients were treated according to the managing methods of each hospital in 2001, the patients were managed using a common clinical path in 2002, on which we conferred and established in 2001. We investigated the change of various outcome indicators before and after implementation of the common clinical path. RESULTS: The background of patients and surgical outcome in 2002 were equal to those in 2001, except in incidence of preoperative urinary tract infection, general anesthesia and blood transfusion, and number of surgeons. Implementation of a common clinical path shortened the pre- and postoperative hospital stay, duration of bed rest, administration of antibiotics and Foley catheter indwelling, and reduced the standard deviation of these indicators. The total medical charge decreased from 515,439 to 491,935 yen. However, outcomes were considerably different among the seven hospitals. Multivariate analyses identified the hospitals, cognitive impairment, preoperative indwelling catheter and preoperative variance as the factors affecting preoperative hospital stay, and the hospitals, co-existing disease, blood transfusion, postoperative urinary tract infection and postoperative variance as factors affecting postoperative stay. Based on these analyses, we determined four exclusion criteria against using a common clinical path: 1) patients requiring examination or surgery other than TURP simultaneously, 2) patients whose ADL disturbance, cognitive impairment, past history and/or coexisting disease are expected to affect postoperative convalescence, 3) patients with a preoperative indwelling catheter just before operation, and 4) patients with preoperative urinary tract infection. By excluding 122 (39.4%) and 129 (43.3%) patients fulfilling the above criteria in 2001 and 2002, respectively, there were reduction in the length of pre- and postoperative hospital stay, and the total admission fee. Furthermore, there were decrease in their standard deviations. CONCLUSIONS: A common clinical path was valid for reducing variance of the critical indicators affecting the clinical course of TURP and shortening the pre- and postoperative stay in the multiple hospitals. It is mandatory to establish the standard perioperative management for TURP from the viewpoint of urologists, under the circumstances of the impending introduction of the Diagnosis Procedure Combination (DPC).