Evaluation of the urethral α/ß ratio and tissue repair half-time for iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy.

PURPOSE: To assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer. METHODS AND MATERIALS: The minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the postimplant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the α/ß ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity. RESULTS: Common dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade ≥ 2 GU toxicity. There was a significant correlation between Grade ≥2 GU toxicity and uBED when the α/ß value was 0.5 or 1 Gy and t1/2 was 0.5-2.5 h. An uBED (α/ß = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade ≥ 2 GU toxicity according to multivariate analysis. CONCLUSIONS: We observed a significant correlation of uBED with GU toxicity when α/ß was 0.5 or 1.0 Gy and t1/2 was 0.5-2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results.

Patient Reported Outcomes in NRG Oncology RTOG 0938, Evaluating Two Ultrahypofractionated Regimens for Prostate Cancer.

PURPOSE: There is considerable interest in very short (ultrahypofractionated) radiation therapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience, and resource allocation benefits. Our objective is to demonstrate that detectable changes in health-related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline scores. METHODS AND MATERIALS: NRG Oncology's RTOG 0938 is a nonblinded randomized phase 2 study of National Comprehensive Cancer Network low-risk prostate cancer in which each arm is compared with a historical control. Patients were randomized to 5 fractions (7.25 Gy in 2 weeks) or 12 fractions (4.3 Gy in 2.5 weeks). The co-primary endpoints were the proportion of patients with a change in EPIC-50 bowel score at 1 year (baseline to 1 year) >5 points and in EPIC-50 urinary score >2 points tested with a 1-sample binomial test. RESULTS: The study enrolled 127 patients to 5 fractions (121 analyzed) and 128 patients to 12 fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The 1-year frequency for >5 point change in bowel score were 29.8% (P < .001) and 28.4% (P < .001) for 5 and 12 fractions, respectively. The 1-year frequencies for >2 point change in urinary score were 45.7% (P < .001) and 42.2% (P < .001) for 5 and 12 fractions, respectively. For 5 fractions, 32.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥11 points (P = .34); for 12 fractions, 30.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥ 11 points (P = .20). Disease-free survival at 2 years is 99.2% (95% confidence interval: 97.5-100) in the 5-fraction arm and 97.5% (95% confidence interval: 94.6-100) in the 12-fraction arm. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity. CONCLUSIONS: This study confirms that, based on changes in bowel and urinary domains and toxicity (acute and late), the 5- and 12-fraction regimens are well tolerated. These ultrahypofractionated approaches need to be compared with current standard radiation therapy regimens.

Reductions in prostatic doses are associated with less acute morbidity in patients undergoing Pd-103 brachytherapy: Substantiation of the rationale for focal therapy.

PURPOSE: Interest in prostate dose reduction or focal treatment exists due to expected reductions in treatment morbidity. Prior analyses have not generally corroborated relationships between prostate or urethral dose and urinary toxicity after brachytherapy, but such analyses have been performed on cohorts all receiving the same prescribed dose. We analyzed patients treated to differing prescription doses to assess acute urinary morbidity with dose reduction. METHODS AND MATERIALS: Patients treated with Pd-103 to either 125 Gy or 90-100 Gy were compared using the International Prostate Symptom Score (IPSS) at 1-month postimplant. Patients in the 90-100 Gy cohort began external beam radiation therapy after their 1-month assessment; thus, toxicities were measured before contribution from external beam radiation therapy. Patient/treatment characteristics were compared to verify subgroup homogeneity. Dose and change in IPSS 1 month after treatment were assessed using a multivariate linear regression model. RESULTS: One hundred ninety-one and 41 patients were treated with 125 Gy versus 90-100 Gy, respectively. Preimplant and postimplant prostate volumes and initial IPSS were similar between groups. Higher prescription dose and increased pretreatment IPSS were independent predictors of increased 1-month IPSS. In addition, every 10 percentage point additional prostate volume receiving a given dose was associated with increase in IPSS after treatment for the same level of pretreatment IPSS. CONCLUSION: Lower prescription dose and decreased volume of high-dose regions to the prostate correlated with reduced acute urinary morbidity after brachytherapy. Our findings suggest that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy.

A novel urethral sparing technique for high-dose-rate prostate brachytherapy after transurethral resection of the prostate.

PURPOSE: The purpose of this study was to assess retrospectively the variability of the urethral dose optimized using a Foley catheter versus urethral contrast injected using a new modified triple-lumen catheter, in CT-based high-dose-rate (HDR) prostate brachytherapy of posttransurethral resection of prostate (TURP) patients. METHODS AND MATERIALS: At our institution, there were six post-TURP patients with prostate carcinoma between July 2014 and April 2016 who underwent transperineal interstitial HDR brachytherapy (16 needles). A custom modified triple-lumen catheter was placed to inject contrast into the TURP defect. Three-dimensional optimal plans using inverse planning simulated annealing algorithm was generated according to radiation therapy oncology group dose requirements. Alternative plans were retroactively generated for comparison using standard technique based on a Foley catheter as a urethral constraint volume for each patient with the same weighting factors. We compared the dosimetry parameters in each planning using Wilcoxon's ranked sum nonparametric test. RESULTS: The median followup of all patients was 17.5 months. No significant genitourinary or gastrointestinal toxicity was noted using this technique. In the dosimetric analysis, the prostate V100 values and TURP urethral V100 were significantly different between plans with and without the contrast (V100 [mean]: 92.4 [%] vs. 94.4 [%], p = 0.046; TURP UV100 [mean]: 1.4 cc vs. 2.2 cc, p = 0.028). There were no statistical differences in the mean values of planning target volume V150%, V200%, and D90, and each bladder V75 and rectum V75. CONCLUSIONS: Post-TURP HDR brachytherapy with urethral contrast showed significantly more volume effect of the TURP defect than that with a Foley catheter alone. Better visualization of the TURP defect should lead to more accurate urethral sparing administration of HDR brachytherapy which is necessary to prevent urethral complication.

Transcorporal artificial urinary sphincter in radiated and non - radiated compromised urethra. Assessment with a minimum 2 year follow-up.

PURPOSE: to assess the efficacy of transcorporal artificial urinary sphincter (AUS) implantation on continence for male stress urinary incontinence in cases of prior surgical treatment or/and radiation failure, and as a first option in radiation patients. MATERIALS AND METHODS: From March 2007 to August 2012, 37 male patients were treated with transcorporal AUS AMS™ 800. Twelve patients had primary placement of transcorporal cuff, a surgical option due to a previous history of radiation and 25 patients had secondary procedure after failure of AUS or urinary incontinence surgery. Functional urinary outcomes were assessed by daily pad use, 24-hour Pad-test and ICIQ-SF questionnaire. Quality of life and satisfaction were assessed based on I-QoL and PGI-I questionnaires. RESULTS: After a median of 32 months, the continence rate (0 to 1 pad) was 69.7%. Median pad test was 17.5g (0-159), mean ICIQ-SF score was 7.3/21 (±5.4) and mean I-QoL score was 93.9/110. A total of 88% of the patients reported satisfaction with the AUS. The 5-year actuarial revision-free for AUS total device was 51%. Patients for primary implant for radiation were not more likely to experience revision than non-radiation patients. Preservation of erections was reported in half of the potent patients. CONCLUSIONS: Transcorporal AUS cuff placement is a useful alternative procedure option for severe male UI treatment, especially in patients with a compromised urethra after prior surgery or radiation. A high continence rate was reported and implantation as first option in radiation patients should be considered.

Transcorporal artificial urinary sphincter in radiated and non - radiated compromised urethra. Assessment with a minimum 2 year follow-up

ABSTRACT Purpose to assess the efficacy of transcorporal artificial urinary sphincter (AUS) implantation on continence for male stress urinary incontinence in cases of prior surgical treatment or/and radiation failure, and as a first option in radiation patients. Materials and Methods From March 2007 to August 2012, 37 male patients were treated with transcorporal AUS AMS™ 800. Twelve patients had primary placement of transcorporal cuff, a surgical option due to a previous history of radiation and 25 patients had secondary procedure after failure of AUS or urinary incontinence surgery. Functional urinary outcomes were assessed by daily pad use, 24-hour Pad-test and ICIQ-SF questionnaire. Quality of life and satisfaction were assessed based on I-QoL and PGI-I questionnaires. Results After a median of 32 months, the continence rate (0 to 1 pad) was 69.7%. Median pad test was 17.5g (0-159), mean ICIQ-SF score was 7.3/21 (±5.4) and mean I-QoL score was 93.9/110. A total of 88% of the patients reported satisfaction with the AUS. The 5-year actuarial revision-free for AUS total device was 51%. Patients for primary implant for radiation were not more likely to experience revision than non-radiation patients. Preservation of erections was reported in half of the potent patients. Conclusions Transcorporal AUS cuff placement is a useful alternative procedure option for severe male UI treatment, especially in patients with a compromised urethra after prior surgery or radiation. A high continence rate was reported and implantation as first option in radiation patients should be considered.

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.

Interstitial rotating shield brachytherapy for prostate cancer.

PURPOSE: To present a novel needle, catheter, and radiation source system for interstitial rotating shield brachytherapy (I-RSBT) of the prostate. I-RSBT is a promising technique for reducing urethra, rectum, and bladder dose relative to conventional interstitial high-dose-rate brachytherapy (HDR-BT). METHODS: A wire-mounted 62 GBq(153)Gd source is proposed with an encapsulated diameter of 0.59 mm, active diameter of 0.44 mm, and active length of 10 mm. A concept model I-RSBT needle/catheter pair was constructed using concentric 50 and 75 µm thick nickel-titanium alloy (nitinol) tubes. The needle is 16-gauge (1.651 mm) in outer diameter and the catheter contains a 535 µm thick platinum shield. I-RSBT and conventional HDR-BT treatment plans for a prostate cancer patient were generated based on Monte Carlo dose calculations. In order to minimize urethral dose, urethral dose gradient volumes within 0-5 mm of the urethra surface were allowed to receive doses less than the prescribed dose of 100%. RESULTS: The platinum shield reduced the dose rate on the shielded side of the source at 1 cm off-axis to 6.4% of the dose rate on the unshielded side. For the case considered, for the same minimum dose to the hottest 98% of the clinical target volume (D(98%)), I-RSBT reduced urethral D(0.1cc) below that of conventional HDR-BT by 29%, 33%, 38%, and 44% for urethral dose gradient volumes within 0, 1, 3, and 5 mm of the urethra surface, respectively. Percentages are expressed relative to the prescription dose of 100%. For the case considered, for the same urethral dose gradient volumes, rectum D(1cc) was reduced by 7%, 6%, 6%, and 6%, respectively, and bladder D(1cc) was reduced by 4%, 5%, 5%, and 6%, respectively. Treatment time to deliver 20 Gy with I-RSBT was 154 min with ten 62 GBq (153)Gd sources. CONCLUSIONS: For the case considered, the proposed(153)Gd-based I-RSBT system has the potential to lower the urethral dose relative to HDR-BT by 29%-44% if the clinician allows a urethral dose gradient volume of 0-5 mm around the urethra to receive a dose below the prescription. A multisource approach is necessary in order to deliver the proposed (153)Gd-based I-RSBT technique in reasonable treatment times.

Is there an increase in genitourinary toxicity in patients treated with transurethral resection of the prostate and radiotherapy? A systematic review.

PURPOSE: Transurethral resection of the prostate (TURP) is considered by some as a risk factor for genitourinary (GU) toxicity after radiotherapy (RT). However, there are conflicting results regarding the interaction between RT and TURP with respect to GU toxicity. The purpose of this report is to review the published data concerning TURP before or after RT and its effect on urinary complication. METHODS AND MATERIALS: A systematic literature review based on database searches in MEDLINE, EMBASE, Pubmed, Ovid, and Chochrane Library. The eligibility criteria of final review were (1) definitive RT for prostate cancer is reported; (2) comparison of GU toxicities between patients with and without TURP is reported; (3) minimum 5 patients after TURP are included. RESULTS: Twelve articles regarding overall GU toxicity, 15 articles regarding urinary incontinence, and 13 articles regarding urinary or bladder neck stricture met eligibility criteria, and they were included in the final review. A quantitative synthesis from the data of selected articles was impossible because of variable grading systems and variable definitions in their comparisons between patients with and without TURP. However, most published articles demonstrated the increased risk of GU toxicity with TURP in patients treated with RT. CONCLUSIONS: Our systematic review strongly suggests that TURP is one of the risk factors of GU toxicity after RT. This needs to be taken seriously when prostate cancer patients with TURP are considered for RT either external beam or brachytherapy.

Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy.

BACKGROUND: Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT), while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control. METHODS: Patients with National Comprehensive Cancer Network (NCCN) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S-) IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3-5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC) Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. RESULTS: From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was -0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52). Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05). At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9-86). Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. CONCLUSIONS: Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical control. The high rate of PSA failure and contralateral local failures in US-IMRT patients, despite careful selection of MRI-screened low-risk patients, serve as a cautionary tale for focal PCa treatments.

Minimizing the number of implantation needles for prostate (125)I brachytherapy: an investigation of possibilities and implications.

PURPOSE: Reduction of the number of implantation needles for prostate brachytherapy will shorten the duration of implantation procedures and possibly reduce trauma-related morbidity. The purpose of this study was to investigate possibilities for the minimization of the number of needles and to investigate the consequences for the dose distribution. METHODS AND MATERIALS: A planning study for six different prostate volumes was performed. The number of needles was minimized by changing fixed 1cm interseed spacing to free interseed spacing within the needles and by increasing the seed activity. Dose-volume parameters of prostate and organs at risk (OAR) bladder, rectum, and urethra were determined. For plans with different needle and seed configurations, the sensitivity for random seed placement inaccuracies was tested. Dose distributions of realized implants based on fixed (n=21) and free interseed spacing (n=21) were compared. RESULTS: The average number of needles (±1 standard deviation) could be reduced from 18.8±3.6 to 12.7±2.9 (-33%) when changing from fixed interseed spacing to free interseed spacing and subsequently to 7.3±1.0 (-42%) by increasing the seed strength from 0.57U to 1.14U. These needle reductions resulted in increased dose inhomogeneity within the prostate and increased sensitivity of dose-volume parameters of the OAR for random geometrical inaccuracies. Introduction of free interseed spacing in our clinic resulted in very satisfactory dose coverage of the prostate (D(90)=172±17Gy), while the average number of needles was reduced by 30%. CONCLUSIONS: Substantial reduction of the number of implantation needles is possible without compromising adequate dose coverage of the prostate. However, the chance of an unpredicted high dose to the OAR increases as fewer needles are used.

Dosimetric evaluation of high-dose-rate interstitial brachytherapy boost treatments for localized prostate cancer.

PURPOSE: To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. MATERIAL AND METHODS: Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters. RESULTS: The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23. CONCLUSION: US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended.

The influence of geometrical changes on the dose distribution after I-125 seed implantation of the prostate.

PURPOSE: After prostate implantation, dose calculation is usually based on a single imaging session, assuming no geometrical changes occur during the months of dose accumulation. In this study, the effect of changes in anatomy and implant geometry on the dose distribution was investigated. MATERIALS AND METHODS: One day, 1 month and 312 months after seed implantation, a combined TRUS-CT scan was made of 13 patients. Based on these scans changes in dose rate distribution were determined in prostate, urethra and bladder and a 'geometry corrected' dose distribution was estimated. RESULTS: When based on the day-1 scan, parameters representing high dose volumes in prostate and urethra were largely underestimated: V150 of the prostate 18+/-10% and V120 of the urethra 47+/-32%. The dose to a 2cm(3) hotspot in the bladder wall (D2cc), however, was overestimated by 31+/-35%. Parameters based on scans 1 month post-implant or later were all within +/-5% of geometry corrected values. CONCLUSION: Values meant to indicate the adequacy of dose coverage of the prostate, V100 and D90, were not influenced by geometrical changes and were independent of the post-implant scan date. Other parameters representing high dose volumes changed strongly within the first month after implantation.

Oral and local anesthesia in the nonsurgical radiofrequency-energy treatment of stress urinary incontinence.

STUDY OBJECTIVE: To demonstrate the feasibility, safety, and patient comfort associated with nonsurgical radiofrequency-energy (RF) tissue micro-remodeling in women with stress urinary incontinence (SUI) given oral and local anesthesia. DESIGN: Prospective, open-label pilot clinical trial (Canadian Task Force classification II-2). SETTING: Department of urology in a major academic teaching hospital in Mexico City, Mexico. PATIENTS: Sixteen women with SUI and hypermobility (based on history and physical examination) with no history of previous definitive incontinence therapy. INTERVENTIONS: Nonsurgical, transurethral, outpatient RF tissue micro-remodeling with women given oral plus local anesthesia. MEASUREMENTS AND MAIN RESULTS: The women had a mean age of 49.7 years (range 30-76 years) and a mean duration of incontinence of 7.6 years (range 1-30 years). The nonsurgical RF micro-remodeling treatment, which was previously demonstrated to be of significant benefit when administered under intravenous (IV) sedation in an outpatient surgicenter setting, was successfully completed in all 16 women. Either the treating physician or the patient had the option to convert to IV sedation during the procedure if there was too much discomfort; however, this did not occur in any of the 16 patients. Thus neither the treating physician nor any patient determined that conversion to IV conscious sedation was required for treatment completion. The first six patients received an oral sedative and oral analgesic as well as a local periurethral anesthetic block with 10 mL of 2% lidocaine. The final 10 patients (63%) received only one oral sedative or analgesic and a total of 10mL lidocaine local anesthetic. Two women who received the maximum oral regimen (both oral sedation and analgesics) experienced nausea and emesis when drinking immediately after treatment, and one of these women also experienced urinary retention, which resolved after 24 hours of catheterization. Immediately before discharge, subjects classified their pain on a scale from zero ("no pain") to 10 ("terrible pain"). Mean score was 1.8, and 38% of subjects selected "zero." CONCLUSION: This pilot trial demonstrated the feasibility, safety, and patient comfort associated with performing a novel new successful technique of nonsurgical RF of the urethra for treatment of SUI, which was previously studied under IV sedation in an outpatient surgery center, on women in an office-based setting using oral plus local anesthesia.

The dosimetry of prostate brachytherapy-induced urethral strictures.

PURPOSE: There is a paucity of data regarding the incidence of urethral strictures after prostate brachytherapy. In this study, we evaluate multiple clinical, treatment, and dosimetric parameters to identify factors associated with the development of brachytherapy-induced urethral strictures. METHODS AND MATERIALS: 425 patients underwent transperineal ultrasound-guided prostate brachytherapy using either (103)Pd or (125)I for clinical T1b/T3a NxM0 (1997, American Joint Committee on Cancer) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. 221 patients were implanted with (103)Pd and 204 patients with (125)I. The median patient age was 68 years (range 48-81 years). The median follow-up was 35.2 months (range 15-72 months). Follow-up was calculated from the day of implantation. Thirteen patients developed brachytherapy-induced strictures, and all strictures involved the membranous urethra. A control group of 35 patients was rigorously matched to the stricture patients in terms of treatment approach; i.e., choice of isotope, plus or minus radiation therapy, and plus or minus hormonal manipulation. Nine of the 13 stricture patients had detailed Day 0 urethral dosimetry available for review. The apex of the prostate gland and the membranous urethra were defined by CT evaluation. Urethral dosimetry was reported for the prostatic urethra, the apical slice of the prostate gland, and the membranous urethra which was defined as extending 20 mm in length. RESULTS: The 5-year actuarial risk of a urethral stricture was 5.3%, with a median time to development of 26.6 months (range 7.8-44.1 months). Of multiple clinical and treatment parameters evaluated, only the duration of hormonal manipulation (>4 months, p = 0.011) was predictive for the development of a urethral stricture. The radiation dose to the membranous urethra was significantly greater in patients with strictures than those without: 97.6% +/- 20.8% vs. 81.0% +/- 19.8% of prescribed minimum prostate dose, mPD (p = 0.031). The urethral dose 20 mm distal to the prostate apex was 57.6% +/- 23.8% vs. 31.5% +/- 13.9% of mPD for the stricture and control patients, respectively (p = 0.011). In addition, the extent of the 75% mPD and 50% mPD levels beyond the prostatic apex was also significantly greater for stricture patients, 16.6 +/- 5.3 mm vs. 11.9 +/- 4.5 mm (p = 0.010) and 19.0 +/- 3.2 mm vs. 16.0 +/- 3.4 mm (p = 0.021), respectively. Dose to the prostatic urethra was not predictive of stricture, but the magnitude and extent of high-dose regions within the prostate were predictive of stricture. Twelve of the 13 patients who developed urethral strictures were successfully managed by dilatation/transurethral incision. To date, 1 of the 12 patients has required a second dilatation. The remaining patient developed an iatrogenic induced injury and was catheter-dependent for 6 months. CONCLUSIONS: After prostate brachytherapy, the actuarial 5-year incidence of urethral strictures is 5.3% with a median time to development of 26.6 months. All strictures involved the membranous urethra and occurred within the first 44 months after brachytherapy. In most cases, membranous urethral strictures are easily managed with dilatation/incision. Factors predicting for the development of a urethral stricture included the magnitude and extent of high-dose regions within the prostate, the mean membranous urethra dose and the dose 20 mm distal to the prostatic apex, the maximum extent along the membranous urethra of certain dose levels, and the duration of hormonal manipulation.

Comparison of seed loading approaches in prostate brachytherapy.

Since uniform seed loading in prostate brachytherapy can produce an intolerably high dose along the urethra, some form of peripheral loading is commonly employed. We define three variants of peripheral loading and compare them in a small, medium, and large prostate in terms of coverage of the planning target volume (PTV), homogeneity, and ability to spare critical structures of excessive dose. Modified uniform loading has at least 2/3 of the seeds occupying sites on a 1 cm cubic grid keyed to the prostate base and the posterior border of the prostate. Nonuniform loading explicitly spares the urethra by using only basal and apical seeds in at least two centrally located needles. Peripheral loading uses higher activity seeds with the posterior implant plane 5 mm anterior to the posterior border of the prostate. The three prostate volumes (18.7, 40.7, and 60.2 cm3 by ultrasound) were expanded to planning volumes (32.9, 60.0, and 87.8 cm3, respectively). The planning volumes (PTVs) were loaded with a 125I seed distribution and activity sufficient to cover 99.7+/-0.3% of the PTV with the prescribed minimal peripheral dose (mPD) of 145 Gy. Activities used ranged from 0.32 to 0.37 mCi/seed (0.41-0.47 U/seed) for the first two approaches and from 0.57 to 0.66 mCi (0.72-0.84 U) for peripheral loading. Modified uniform loading produced the most uniform distribution based on dose-volume histograms and the volume receiving >150% of prescribed dose. All the approaches are capable of constraining the superior-inferior dose profile (the urethral path) to less than 150% of the mPD, but the nonuniform approach with explicit urethral sparing kept the urethral dose below 120% of the mPD. Dose profiles for the three approaches along the posterior-anterior midline axis are comparable near the urethra, but peripheral and nonuniform approaches have extended regions where the dose is >150% of mPD. These regions approach within 10 mm of the rectum or urethra, so these two approaches require greater accuracy in intraoperative execution of the plan. Although each of the three planning approaches can achieve the treatment goals of adequate coverage and critical structure sparing, modified uniform loading has a more homogeneous dose distribution. This approach may be more forgiving of systematic errors in seed placement.

Necrosis of the urethra and tissue sloughing: a delayed complication after transurethral microwave thermotherapy.

Transurethral microwave thermotherapy is a minimally invasive treatment for benign prostatic hyperplasia designed to destroy hyperplastic tissue without damaging the urethra. We present an unexpected complication of prostatic urethral necrosis and tissue sloughing after thermotherapy and discuss its possible cause.

Quantification of the 3-D electromagnetic power absorption rate in tissue during transurethral prostatic microwave thermotherapy using heat transfer model.

Experiments were performed in a tissue microwave-equivalent phantom gel to quantitatively examine the volumetric heating produced by a microwave antenna with a peripheral cooling system for the transurethral prostatic thermotherapy. Based on previous research, expression for the specific absorption rate (SAR) of microwave energy in the gel was extended to three dimensions, which includes its dependence on radial, angular, and axial direction. A theoretical heat transfer model was developed to study the temperature distribution in the gel by introducing this proposed SAR expression. The parameters in this expression and the convection coefficient due to the chilled water running around the antenna were determined using a least-square residual fit of the theoretical temperature predictions to the experimentally measured steady-state temperature field within the gel. The analytical expression of the three-dimensional SAR distribution obtained in this study will help provide a better understanding of the microwave heating pattern in the prostatic tissue and, thus, to aid in designing improved applicators. It can also be used in the future as an accurate input to heat transfer models which predict temperature distributions during the transurethral microwave thermotherapy.

Thermoregulation in the canine prostate during transurethral microwave hyperthermia, Part I: Temperature response.

In this research, experiments were performed to study thermoregulation in the canine prostate during microwave hyperthermia. The transurethral thermal therapy (T3) system provided by Urologix, Inc. was used to impose microwave heating in the canine prostate. Five types of temperature responses to different microwave power levels as time varies, including both damped and sustained oscillatory temperature responses, have been observed. Decreases in prostatic tissue temperature during the microwave heating are believed to be caused by the increase in local blood flow stimulated by tissue temperature elevations. In this study, the characteristic temperatures and time associated with each response. This work will help to provide a better understanding of how tissue temperature is regulated within the canine prostate during transurethral microwave hyperthermia. Results of the present study offer an experimental foundation for a more detailed theoretical analysis on the temperature distribution based on the power input and local blood perfusion.

[Two cases of cavity formation in prostatic urethra after transurethral microwave thermotherapy (TUMT) with Prostatron].

The Prostatron device, developed by Dr. Devonec, provides microwave heating of the prostate and simultaneous conductive cooling of the urethra. Treatment with Prostatron (transurethral microwave thermotherapy: TUMT) of BPH can be performed in a single session, and the urethra, the rectum and the surrounding tissue are protected with the temperature monitoring system. TUMT with Prostatron may be more suitable for a small adenoma with mild symptoms than a large adenoma with severe symptoms, because objective improvement is rarely observed compared with subjective improvement. We have treated 40 cases of BPH with Prostatron (Prostasoft 2, max. energy: 50 watt, max. urethral temperature: 44.5 degrees C, max. rectal temperature: 42.5 degrees C) since March 1993. Among them, there were 2 cases of large cavity formation involving the prostatic urethra. With cavity formation, TUMT may have its place in the treatment of a large adenoma with severe urinary symptoms, but loses its advantage in the prevention of persistent urinary infection and retrograde ejaculation, especially in the treatment of a small adenoma in a younger patient with mild urinary symptoms. It is unknown why such cavity formation occurred only in 2 patients among 40 equally treated cases, but the causes of cavity formation and safety of TUMT should be evaluated again, even though no injury to the rectum and the external urethral sphincter were detected. We report these 2 cases, and causes of cavity formation and discuss the prospects of TUMT.