Patients Undergoing Prostate Brachytherapy Research Articles

Anesthesia concerns in prostate brachytherapy: An institutional experience.

Prostate cancer is a common cancer found in men worldwide. Brachytherapy is an established modality used for the treatment of these patients. Although anesthetic management of such patients is challenging but the ideal anesthetic technique has not yet been established. Our study aims to identify the most efficacious anesthetic technique for perioperative management of prostate cancer patients undergoing brachytherapy. Retrospective analysis of ten patients who underwent 16 brachytherapy sessions under combined spinal epidural (CSE) anesthesia between April 2016 and December 2016 was done. The data were collected, tabulated using MS Excel, and statistically analyzed with EPI Info 6 and SPSS-16 statistical software (SPSS Inc. Chicago, USA) to draw relative conclusions. The median peak sensory dermatome level achieved was T6 and the median maximum motor block achieved was grade 2. The mean (± standard deviation (SD)) time to sensory regression to T10 (range T5-T8) dermatome was found to be 118.00 ± 47.110 (range = 0-238) minutes. Despite the presence of co-morbidities, minor intraoperative complications were observed only in two patients. The postoperative numerical rating scale (NRS) was less than 4 in all patients during the first 24 hours. None of our patients complained of nausea, vomiting, pruritus and respiratory depression. The mean (± SD) patient satisfaction score was 44.40 ± 0.871 (range : 1-5) at the end of 24 hours. CSE anesthesia is a safe and effective technique for anesthetic management of patients undergoing prostate brachytherapy.

Prostate brachytherapy under hypnosedation: A prospective evaluation

PurposeHypnosedation (HS) for brachytherapy has been proposed in patients with prostate cancer and has been evaluated. Materials and Methods79 patients were treated with brachytherapy under HS. The Visual Analog Scale questionnaire was used to assess comfort and anxiety and the lowest, mean, and highest level of pain. Data for 79 patients who underwent general anesthesia (GA) and 37 patients who underwent spinal anesthesia (SA) treated at the same period were compared with HS group in terms of medication and treatment duration. Results11 patients (13.9%) requested a GA, because they did not reach the hypnotic level. For the remaining 68 patients, the mean pain and comfort scores evaluated just after the intervention were 3.1 and 7.4, respectively. At 8 weeks, the scores were 2.8 and 7.5, respectively. 66 patients (97%) would choose this approach again and recommend it to other patients. The patients in the HS group received significant less medications than in the GA (remifentanil, propofol, kétamine, phenylephrine, ephedrine…) or SA (sufentanil, midazolam, morphine, bupivacaine…) groups with mean values of 3.1 vs. 7.9 vs. 5.6 (p < 0.0001), respectively. HS increased the mean time of surgery room occupation by 12 min vs. GA and by 20 min vs. SA. However, the recovery room occupation is avoided with HS (GA = 61 min and SA = 67 min) and a shorter duration of a need for a urinary catheter was noted. ConclusionsHS is a feasible and comfortable method of anesthesia and a good alternative to GA and SA for patients undergoing prostate brachytherapy, with reduced treatment duration and number of medications.

622 - Perioperative search for circulating tumor cells in patients undergoing prostate brachytherapy for clinically nonmetastatic prostate cancer

622 - Perioperative search for circulating tumor cells in patients undergoing prostate brachytherapy for clinically nonmetastatic prostate cancer

Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer.

Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT). Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative) and again immediately after the surgical manipulation (intraoperative). Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs) using the CellSearch System. While no preoperative samples showed CTCs (0%), they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012). Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA) at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

Impact of Gleason Pattern 5 on outcomes of patients with prostate cancer and iodine-125 prostate brachytherapy.

BackgroundThe Gleason grading system is a powerful predictor of prostate cancer (PCa) prognosis. Gleason scores (GS) of 8–10 are considered as a single high-risk grade category, and Gleason Pattern 5 (GP5) predicts biochemical recurrence. We report the clinical outcomes of patients treated with 125I prostate brachytherapy for clinically localized PCa and prognosis in the presence or absence of GP5.MethodsWe enrolled 316 patients with T1c–T2N0M0 PCa and undergoing prostate brachytherapy treatment. All patients were followed up for ≥ 1 year. The primary endpoint was biochemical recurrence-free survival. Biochemical recurrence was defined by the Phoenix criteria. Survival curves were calculated by the Kaplan–Meier method, and the prognostic impact of biochemical recurrence was analyzed using a Cox proportional hazards model.ResultsThe 5-year biochemical recurrence-free survival rate for all patients was 95.2%, and according to the D’Amico risk classification criteria, the rates were 98.7% for patients in low-risk, 96.9% in intermediate-risk, and 81.1% in high-risk groups (P < 0.0001). The 5-year biochemical recurrence-free survival rates for patients with GS8 or GS9–10 were 87.7% and 61.5%, respectively (P = 0.0057). Multivariate analysis found that GS and clinical T stage were independent predictors of biochemical recurrence.ConclusionsThe presence of GP5 in GS9–10 prostate cancer has a worse prognosis than GS8 prostate cancer in the absence of GP5 for patients undergoing prostate brachytherapy.

Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer

Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer

Five Year Prostate-specific Antigen Outcomes after Caesium Prostate Brachytherapy

AimsTo report 5 year prostate-specific antigen outcomes in men undergoing prostate brachytherapy with caesium 131 at a single institution. Materials and methodsAll patients who underwent prostate brachytherapy with caesium 131 at our institution and had at least 24 months of follow-up were included in this study. The results are reported by risk group (low, intermediate and high) as well as by treatment received (monotherapy, combination therapy or trimodal therapy). The Phoenix definition (absolute nadir plus 2 ng/ml) was used to define biochemical freedom from disease (BFD). ResultsFour hundred and eighty-five patients underwent prostate brachytherapy with caesium 131 at our institution and 367 patients had at least 24 months of follow-up and were included in this analysis. Using the Phoenix criteria, 5 year actuarial BFD was 96.0% for patients in the low-risk category, 92.7% for patients in the intermediate-risk category and 82.9% for patients in the high-risk category. By treatment category, 95.7% of men treated with monotherapy had BFD, 84.9% of men treated with combination therapy had BFD and 92.0% of men treated with trimodal therapy had BFD. ConclusionsThe present study showed that prostate brachytherapy with caesium 131 achieves excellent oncological outcomes at 5 years.

A Prospective Quasi-Randomized Comparison of Intraoperatively Built Custom-Linked Seeds Versus Loose Seeds for Prostate Brachytherapy

To compare dosimetric parameters, seed migration rates, operation times, and acute toxicities of intraoperatively built custom-linked (IBCL) seeds with those of loose seeds for prostate brachytherapy. Participants were 140 patients with low or intermediate prostate cancer prospectively allocated to an IBCL seed group (n=74) or a loose seed group (n=66), using quasirandomization (allocated by week of the month). All patients underwent prostate brachytherapy using an interactive plan technique. Computed tomography and plain radiography were performed the next day and 1 month after brachytherapy. The primary endpoint was detection of a 5% difference in dose to 90% of prostate volume on postimplant computed tomography 1 month after treatment. Seed migration was defined as a seed position >1 cm from the cluster of other seeds on radiography. A seed dropped into the seminal vesicle was also defined as a migrated seed. Dosimetric parameters including the primary endpoint did not differ significantly between groups, but seed migration rate was significantly lower in the IBCL seed group (0%) than in the loose seed group (55%; P<.001). Mean operation time was slightly but significantly longer in the IBCL seed group (57 min) than in the loose seed group (50 min; P<.001). No significant differences in acute toxicities were seen between groups (median follow-up, 9 months). This prospective quasirandomized control trial showed no dosimetric differences between IBCL seed and loose seed groups. However, a strong trend toward decreased postimplant seed migration was shown in the IBCL seed group.

Long-term follow-up of International Prostate Symptom Score (IPSS) in men following prostate brachytherapy

To investigate variation in the International Prostate Symptom Score (IPSS) in men following prostate brachytherapy. From January 2004 to November 2009, 524 consecutive patients underwent prostate brachytherapy either alone or in combination with external beam radiation therapy for T1c-T3b prostate cancer. The IPSS was assessed preimplant and at 1, 6, 12, 24, 36, and 48 months after treatment. Clinical and treatment-related factors were assessed for correlations with the IPSS increase. The mean preimplant IPSS was 7.4, with the greatest mean score of 16.0 at 1 month. At 6 months, the mean total IPSS had decreased to 11.5, but it was still statistically significantly greater than that at baseline (<0.001). At 12 months, the IPSS was decreased to 8.6, slightly greater than baseline (p = 0.001). The IPSS of 45.4 % (69/152) patients gradually returned to preimplant levels and that of 71.1 % (108/152) patients returned to within 3 points of the baseline at 24 months. At 24, 36, and 48 months after seed implantation, the IPSS was 8.6, 7.7, and 8.2, respectively, and none of these values differed statistically significantly from baseline (p > 0.05). Sixteen patients (3.1 %) showed AUR, and 11 patients required catheterization. On univariate and multivariate analyses, the IPSS increase was best predicted by lower preimplant IPSS. In our series, IPSS after prostate brachytherapy peaked at 1 month and gradually returned to approximately baseline at 24 months. The IPSS increase was best predicted by lower preimplant IPSS.

Impact of comorbidity in elderly prostate cancer patients treated with brachytherapy.

To analyze the correlations among comorbidity and overall survival (OS), biochemical progression-free survival (b-PFS) and toxicity in elderly patients with localized prostate cancer treated with (125)I brachytherapy. Elderly men, aged ≥65 years, with low-intermediate risk prostate cancer, were treated with permanent (125)I brachytherapy as monotherapy. Comorbidity data were obtained from medical reports using age-adjusted Charlson comorbidity index (a-CCI). The patients were categorized into two age groups (<75 and ≥75 years old), and two comorbidity score groups (a-CCI ≤3 and >3). Toxicity was scored with Radiation Therapy Oncology Group (RTOG) scale. From June 2003 to October 2009, a total of 92 elderly patients underwent prostate brachytherapy, including 57 men (62%) with low-risk prostate cancer, and 35 men (38%) with intermediate-risk prostate cancer. The median age of patients was 75 years (range, 65-87 years). Forty-seven patients (51%) had a-CCI ≤3 and 45 patients (49%) a-CCI >3. With a median follow-up period of 56 months (range, 24-103 months), the 5-year actuarial OS and b-PFS were 91.3% and 92.4% respectively, without statistical significance between two Charlson score groups. Toxicity was mild. None of the patients experienced gastrointestinal (GI) toxicity, and only 4 patiens (4%) experienced late genitourinary (GU) grade-3 (G3) toxicity. No correlation between acute GU and GI toxicity and comorbidity was showed (P=0.50 and P=0.70, respectively). Our data suggest that elderly men with low-intermediate risk prostate cancer and comorbidity can be considered for a radical treatment as (125)I low-dose rate brachytherapy.

Assessment of antimicrobial prophylaxis to prevent perioperative infection in patients undergoing prostate brachytherapy: multicenter cohort study

To propose an appropriate prophylactic antimicrobial therapy for patients undergoing brachytherapy, we evaluated the relationships between various antimicrobial prophylaxis (AMP) protocols and the incidence of postimplant infections in a multicenter cohort study conducted in Japan. The records of 826 patients with localized prostate cancer who underwent a transperineal (125)I brachytherapy procedure between January 2009 and December 2010 were retrospectively reviewed. Perioperative infections, including surgical site and remote infections, were recorded up to postoperative day 30. A total of 6 (0.73%) patients had a perioperative infection following seed implantation, of whom all received AMP for 1 or more days. None of the patients who received a single-dose protocol of AMP using fluoroquinolone p.o. or penicillin with a beta-lactamase inhibitor i.v. developed a perioperative infection. Statistical analysis showed that a single-dose protocol was more significantly related to a lower risk of perioperative infection as compared to the other AMP protocols examined (p = 0.045). Furthermore, our results indicated that bacteriuria and preoperative hair removal were risk factors of perioperative infection with statistical significance (p = 0.007, p = 0.004). Analysis of patient clinical parameters, including age, American Society of Anesthesiologists score, diabetes mellitus, prostate volume, numbers of implanted seeds and needle punctures, operation time, and indwelling duration time of the Foley catheter, did not reveal significant differences in terms of perioperative infection. Our results indicated that a single-dose AMP protocol is sufficient to prevent perioperative infections following seed implantation. On the other hand, AMP is only one of several measures to prevent perioperative infectious complications. It is necessary to know that the patient must have no bacteriuria and that preoperative hair removal should be avoided.

A comparison of the impact of isotope (125I vs. 103Pd) on toxicity and biochemical outcome after interstitial brachytherapy and external beam radiation therapy for clinically localized prostate cancer

PurposeTo compare biochemical outcomes and morbidity associated with iodine-125 (125I) and palladium-103 (103Pd) brachytherapy as part of combined modality therapy for clinically localized prostate cancer. Methods and MaterialsBetween October 2002 and December 2008, 259 patients underwent prostate brachytherapy (125I prescription dose, 110Gy: n=199; 103Pd prescription dose, 100Gy: n=60) followed by external beam radiotherapy (median dose, 50.4Gy). Eighty-seven patients also received neoadjuvant androgen deprivation therapy. Toxicities were recorded with CTCAE v 3.0, International Prostate Symptoms Score (IPSS), and International Index of Erectile Function questionnaires. ResultsOverall, acute Grade ≥2 genitourinary toxicity occurred in 21% and 30% of patients treated with 125I and 103Pd, respectively (p=0.16). There were no significant differences in IPSS change or urinary quality-of-life scores between the isotopes at 4, 6, or 12 months (p=0.20, 0.21, and 1.0, respectively). IPSS resolution occurred at a median of 11 and 6 months for 125I and 103Pd patients, respectively (p=0.03). On multivariate analysis, only the use of neoadjuvant androgen deprivation therapy was predictive of time to IPSS resolution (p=0.046). Late Grade ≥2 gastrointestinal toxicity occurred in 7% of 125I patients and 6% of patients treated with 103Pd. Of 129 potent patients at baseline, there was better erectile function in patients who received 103Pd (p=0.02); however, the followup was shorter for these patients. The 5-year prostate-specific antigen relapse-free survival for 125I and 103Pd patients was 95.2% and 98.2% (p=0.73), respectively. ConclusionThere were no differences in acute or long-term genitourinary or gastrointestinal toxicity between 125I and 103Pd in combined modality therapy for prostate cancer. There may be less erectile toxicity with the use of 103Pd; however, additional followup of these patients is needed. There was no significant difference in 5-year prostate-specific antigen relapse-free survival between 103Pd and 125I.

Testosterone recovery after permanent prostate seed implantation in patients with neoadjuvant hormonal therapy.

e15067 Background: The PSA kinetics in patients undergoing prostate brachytherapy with neoadjuvant hormonal therapy (NHT) is dependent on the recovery of serum testosterone(T) levels. When NHT was done, determination of PSA nadir is sometimes very confusing because of variety pattern of testosterone recovery. In this study, we assessed the duration of testosterone recovery and its effect on PSA kinetics in Asian (Japanese) men. Methods: From March 2004 to September 2010, 612 patients underwent I125 seed implantation in our institution. The records of 306 patients with NHT and a minimum of 2 years of follow-up were reviewed. Among those, 243 had serum testosterone level measurement every 3-6 months. All patients had at least 2 years of follow-up and were ceased androgen ablation after seed implantation. Prognostic factors for testosterone recovery were examined using multivariate Cox regression analysis. Results: Of 243 patients (age 48-81) with T1-T2 N0M0 prostate cancer, 207 had appropriate data. NHT included maximum androgen blockade (MAB) in 47 patients (22.7%), LHRH analog (LHRHa) in 157 (75.8%) and anti-androgen agent in 3(1.5%). The median duration of NHT was 11 months (range 3-72M). 94.7% of patients (n=196) recovered normal T levels (7.2 nmol/l) and median time to recover was 6.9 months (MAB group 9.0M, LHRHa group 6.5M). When PSA nadir was defined after 6.9M (207 days) of brachytherapy, 2 patients (4.3%) had biochemical failure (BF; nadir+2ng/dl) and 2 (4.3%) had PSA bounce (PB) in MAB group while 3 patients (1.9%) had BF and 7 (4.5%) had PB in LHRHa group. Total BF free rate was 5.8% and PSA bounce rate was 16.0%. 11 patients (5.3%, median NHT duration 10 months) did not recover normal T levels. On multivariate analysis, younger age (p=0.016, 95% C.I. 0.945-0.994) and the use LHRHa as compared with MAB (p=0.004. 95% C.I. 0.028-0.504) could be the prognostic factors for testosterone recovery. The duration of NHT was not significant (p=0.211) in this study. Conclusions: 78.3% and 95.4% of patients recovered normal serum testosterone levels within a year and 2 years, respectively. Defining PSA nadir according to T recovery seems useful in appropriate follow-up of patients undergoing brachytherapy with NHT.

Two-Year PSA Outcomes After Cesium Prostate Brachytherapy

92 Background: Given the long natural history of prostate cancer, long term follow up is needed to definitively know the efficacy of a new treatment, in this case 131Cs brachytherapy. However, it is also important to report on short term outcomes to ensure that this treatment is on course to provide equivalent outcomes as compared to existing treatment options. This reports two year PSA outcomes in men undergoing prostate brachytherapy with cesium 131 at a single institution. Methods: All patients who underwent prostate brachytherapy with 131Cs and had at least 24 months of follow up were included in this study. Results are reported for the total cohort and stratified by risk group as well as treatment received (monotherapy, combination therapy, or trimodal therapy). The Phoenix definition was used to define biochemical disease free survival (bDFS). Outcomes were analyzed using descriptive statistics. Results: 115 patients underwent prostate brachytherapy with 131Cs and had at least 24 months of follow up...

Two-year PSA outcomes after cesium prostate brachytherapy.

92 Background: Given the long natural history of prostate cancer, long term follow up is needed to definitively know the efficacy of a new treatment, in this case 131Cs brachytherapy. However, it is also important to report on short term outcomes to ensure that this treatment is on course to provide equivalent outcomes as compared to existing treatment options. This reports two year PSA outcomes in men undergoing prostate brachytherapy with cesium 131 at a single institution. Methods: All patients who underwent prostate brachytherapy with 131Cs and had at least 24 months of follow up were included in this study. Results are reported for the total cohort and stratified by risk group as well as treatment received (monotherapy, combination therapy, or trimodal therapy). The Phoenix definition was used to define biochemical disease free survival (bDFS). Outcomes were analyzed using descriptive statistics. Results: 115 patients underwent prostate brachytherapy with 131Cs and had at least 24 months of follow up. Fifty two (45.2%) patients were classified as low risk, 52 (45.2%) were intermediate risk, and 11 (9.6%) were high risk. Eighty one patients were treated with prostate brachytherapy as monotherapy, including six patients who received androgen-deprivation therapy (ADT) in combination with their brachytherapy. Twenty five patients received combination therapy, and 9 patients received trimodal therapy. Specifics of bDFS rates and PSA data are reported in the table. Of the 115 patients four had biochemical recurrence. Two patients died during the study period, both due to causes other than prostate cancer, and one patient was unwilling to obtain a PSA at the 24 month follow up time point. Conclusions: The first 115 patients who have undergone prostate brachytherapy with 131Cs at our institution have a bDFS rate of 96.4% 24 months after their procedure. With the very important caveat that only short term results are reported, 131Cs appears to be on course to achieve results comparable to those achieved with iodine 125 (125I) and palladium 103 (103Pd). [Table: see text] No significant financial relationships to disclose.

Impact of Hormonal Therapy on Intermediate Risk Prostate Cancer Treated With Combination Brachytherapy and External Beam Irradiation

We assessed the impact of androgen suppressive therapy on biochemical failure in patients with intermediate risk prostate cancer treated with brachytherapy and external beam irradiation. From 1994 to 2006, 432 patients with intermediate risk prostate cancer as defined by the National Comprehensive Cancer Network were treated with low dose rate brachytherapy and external beam irradiation with or without 9 months of androgen suppressive therapy. Gleason score was 7 in 76% of cases and prostate specific antigen was 1.4 to 20 ng/ml (median 7.6). Of the patients 350 received androgen suppressive therapy and 82 did not. The biologically effective dose was 142 to 280 Gy2 (median 206). Followup was 23 to 155 months (median 56). The overall 8-year biochemical failure-free rate using the Phoenix definition in patients with vs without androgen suppressive therapy was 92% vs 92% (p = 0.4). The therapy had no significant impact on the biochemical failure-free rate in patients with Gleason score 7 (92% vs 90.5%, p = 0.55), prostate specific antigen 10 to 20 ng/ml (92% vs 100%, p = 0.32), T2b-T2c disease (89.5% vs 97%, p = 0.27) and more than 1 intermediate risk feature (90% vs 100%, p = 0.2). We addressed the relative importance of radiation dose vs hormonal therapy for intermediate risk prostate cancer. With high biologically effective dose combination treatment androgen suppressive therapy did not have a significant impact on the 8-year biochemical failure-free rate. We question its routine use in this setting.

Is there Decreased Duration of Acute Urinary and Bowel Symptoms after Prostate Brachytherapy with Cesium 131 Radioisotope?

Recently a new isotope, Cesium 131, has been introduced for use in prostate brachytherapy in hopes of decreasing the duration of the bothersome urinary and bowel side effects which occur after the procedure. The present study evaluates the severity and time to resolution of acute urinary and bowel symptoms in men undergoing prostate brachytherapy with Cesium 131. All patients undergoing prostate brachytherapy with Cesium 131 at our institution were asked to complete the Expanded Prostate Cancer Index Composite (EPIC) pre-operatively and at 2 weeks, 4 weeks, 2 months, 3 months, and 6 months postoperatively. Patients who have completed at least 2 EPIC surveys were included in this study. Student's t test was used for comparing the difference between the means. To date, 94 patients have undergone prostate brachytherapy with Cesium 131. 79 patients had at least 2 completed EPIC surveys. The mean EPIC urinary scores at baseline, 2 weeks, 4 weeks, 2 months, 3 months, and 6 months were 84.77, 58.69, 62.82, 66.06, 79.03, 87.03, respectively. The mean EPIC bowel scores at baseline, 2 weeks, 4 weeks, 2 months, 3 months and 6 months were 83.86, 51.44, 56.72, 62.46, 80.12, 84.8, respectively. Urinary and bowel summary scores were significantly different from baseline at 2 weeks, 4 weeks and 2 months. The bowel and urinary summary scores returned to baseline at 3 and 6 months, respectively. Similarly all the bowel subscales including function and bother returned to baseline at 3 months. Urinary subscales including function, bother, incontinence and irritative symptoms returned to baseline at 6 months. In patients undergoing prostate brachytherapy with Cesium 131, postoperative bowel and urinary symptoms peaked between 2 to 4 weeks and returned to baseline at 3 and 6 months, respectively. The symptom scores suggest early peak and decreased duration of symptoms probably because of shorter half life of Cesium 131 radioisotope.

Distant and local recurrence in patients with biochemical failure after prostate brachytherapy

Purpose To analyze the patterns of failure after the brachytherapy management of localized prostate cancer. Methods and materials From 1990 to 2008, 2869 patients underwent prostate brachytherapy and 213 experienced a prostate-specific antigen (PSA) failure by the Phoenix definition. Of these 213 patients, 33.5% were low, 18.5% intermediate, and 58% high risk. Results Of the 119 patients biopsied, 36 (30%) had a least one positive posttreatment biopsy. In univariate and multivariate analyses, PSA doubling time was the most predictive of a positive biopsy. Patients with doubling times ≤3, >3–6, ≥6–10, and >10 months had positive biopsy rates of 9%, 18%, 36%, and 42%, respectively ( p = 0.01). The actuarial rate of remaining free from distant metastases at 10 years was 73%. Patients with PSA doubling times of ≤3, >3–6, >6–10, and >10 months had freedom from distant metastases rates of 0%, 74%, 78%, and 94.5% at 10 years, respectively ( p < 0.0001). In multivariate analysis, PSA doubling time and time to PSA failure were the most significant predictors of developing distant metastases. Conclusions About one third of patients harbor a component of local failure and one fourth demonstrate clinical metastases. PSA doubling time can be used to help predict the source of a rising PSA.

Primary Causes of Death After Permanent Prostate Brachytherapy

To evaluate the primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and high-risk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily resulted from an excess of cardiovascular deaths. Changes in lifestyle to improve cardiovascular health may improve overall survival in patients with clinically localized prostate cancer.

Development and pilot testing of the Neuromuscular Blockade Advisory System

The neuromuscular blocker advisory system (NMBAS) is a computer program developed to provide advisory guidance to anesthesiologists on the timing and dose of rocuronium to paralyze patients during surgery. It is believed that the use of such a system will administer the minimally effective amount of drug, maintaining the patient in a state of paralysis that is useful for surgery yet easily reversible. This will improve patient safety and result in more efficient care. In this paper we present the NMBAS, its basic methodology, and its development though a pilot study. Novel methods of handling neuromuscular response data are presented, including relaxation measurement and the enhanced-train-of-four sensing modality. New methods of handling nonlinearities at the neuromuscular junction to allow application of adaptive control techniques are presented. A novel form of modelling combining model swapping and RLSE adaptation to accommodate the patient variation seen with NMB drugs is introduced. A pilot study testing the NMBAS was undergone to prepare the NMBAS for application in a full clinical trial, in which patients undergoing prostate brachytherapy surgeries using rocuronium for intubation were admitted.