International Prostate Symptom Score Resolution Research Articles

A Phase 2 Randomized Pilot Study Comparing High-Dose-Rate Brachytherapy and Low-Dose-Rate Brachytherapy as Monotherapy in Localized Prostate Cancer

PurposeTo compare health-related quality of life (HRQOL) of high-dose-rate brachytherapy (HDRB) versus low dose-rate brachytherapy (LDRB) for localized prostate cancer in a multi-institutional phase 2 randomized trial. Methods and MaterialsMen with favorable-risk prostate cancer were randomized between monotherapy brachytherapy with either Iodine-125 LDRB to 144 Gy or single-fraction Iridium-192 HDRB to 19 Gy. HRQOL and urinary toxicity were recorded at baseline and at 1, 3, 6, and 12 months using the Expanded Prostate Cancer Index Composite (EPIC)-26 scoring and the International Prostate Symptom Score (IPSS). Independent samples t test and mixed effects modeling were performed for continuous variables. Time to IPSS resolution, defined as return to its baseline score ±5 points, was calculated using Kaplan-Meier estimator curves with the log-rank test. A multiple-comparison adjusted P value of ≤.05 was considered significant. ResultsLDRB and HDRB were performed in 15 and 16 patients, respectively, for a total of 31 patients. At 3 months, patients treated with LDRB had a higher IPSS score (mean, 15.5 vs 6.0, respectively; P = .003) and lower EPIC urinary irritative score (mean, 69.2 vs 85.3, respectively; P = .037) compared with those who received HDRB. On repeated measures at 1, 3, 6, and 12 months, the IPSS (P = .003) and EPIC urinary irritative scores (P = .019) were significantly better in the HDR arm, translating into a lower urinary toxicity profile. There were no significant differences in the EPIC urinary incontinence, sexual, or bowel habit scores between the 2 groups at any measured time point. Time to IPSS resolution was significantly shorter in the HDRB group (mean, 2.0 months) compared with the LDRB group (mean, 6.0 months; P = .028). ConclusionsHDRB monotherapy is a promising modality associated with a lower urinary toxicity profile and higher HRQOL in the first 12 months compared with LDRB.

Quantitative analysis of genitourinary toxicity after iodine-125 brachytherapy for localized prostate cancer: Followup of the International Prostate Symptom Score and Overactive Bladder Symptom Score

PurposeTo analyze genitourinary toxicity by followup of the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) after prostate brachytherapy. Methods and MaterialsSix hundred eighty patients were treated with iodine-125 brachytherapy for localized prostate cancer. IPSS, OABSS, and two categories of IPSS questions (storage symptom score [IPSS-S] and voiding symptom score [IPSS-V]) were evaluated. ResultsThe median followup was 54 months (range, 24–108). All scales showed rapid increases followed by gradual decreases. The median times to IPSS peak and resolution were 1 and 6 months, respectively. The resolution rates of IPSS, IPSS-S, IPSS-V, and OABSS at the last followup were 84.2%, 86.3%, 89.5%, and 83.0%, respectively. The difference between IPSS baseline and peak was greater for larger preimplant prostate volumes (≥25 mL, p = 0.004). The time to resolution was longer for higher biologic effective dose (BED) (≥210 Gy, p = 0.019 [IPSS]), in those with larger prostate volumes (≥25 mL, p = 0.025 [OABSS]), in younger patients (younger than 70 years, p = 0.043 [IPSS-S]), and in those with androgen deprivation therapy (ADT) use (p = 0.049 [IPSS-V]). Urge incontinence, included in the OABSS, was observed more commonly in older patients (75 years and older, p = 0.018), with ADT use (p < 0.001), and for higher BED (≥210 Gy, p = 0.006). ConclusionsThe IPSS and OABSS showed similar patterns of change. Urinary symptoms improved more rapidly in those with high baseline IPSS levels. The OABSS was useful for following urinary symptoms after prostate brachytherapy. Age, ADT use, preimplant prostate volume, and BED were significantly associated with urinary outcomes.

Does supplemental external beam radiation therapy impact urinary, bowel, and erectile function following permanent prostate brachytherapy?: results of two prospective randomized trials.

PurposeTo evaluate the impact of supplemental external beam radiation therapy (EBRT) prior to permanent prostate brachytherapy on long term urinary, bowel, and erectile function.Material and methodsPatient administered urinary, bowel, and erectile quality of life (QoL) instrument were obtained prior to treatment and following brachytherapy. The study population was comprised of the 457 patients who were alive as of June 2016, had been randomized to two markedly different supplemental EBRT dose regimens and a third arm without supplemental EBRT, and had completed the June 2016 QoL survey. The need for urinary or bowel surgical intervention was prospectively recorded during routine follow-up. Multiple parameters were evaluated for effect on outcomes.ResultsThe urinary catheter was removed on day 0 in 92.1% of patients and 0.4% required a post-implant transurethral prostatic resection (TURP). On average, the International Prostate Symptom Score (IPSS) normalized at week 14. The 10-year rate of urethral strictures was 5.3%. No significant differences were discerned between baseline and post-implant rectal function assessment score (RFAS), and no patient developed a rectal ulcer or fistula. The 10-year potency preservation rate was 50.3%. Supplemental EBRT did not affect urinary, bowel, or erectile function. Urethral strictures were most closely related to bulbomembranous urethral brachytherapy doses, post-implant rectal function to pre-implant hemorroidal bleeding, and RFAS and erectile function to pre-brachytherapy international index of erectile function and age.ConclusionsSupplemental EBRT did not significantly effect catheter dependency, IPSS resolution, urethral stricture rate, the need for post-implant TURP, bowel, or erectile function. Careful attention to brachytherapy dose distributions appears to be most important in minimizing post-brachytherapy morbidity.

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

PurposeWe 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 MaterialsWe 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. ResultsIPSS 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. ConclusionsNADT 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.

Decline in acute urinary toxicity: A long-term study in 2011 patients with prostate brachytherapy within a provincial institution

To determine whether acute urinary toxicity rates improve with the overall experience of a large prostate brachytherapy program. From 1998 to 2009, 2937 patients were treated with prostate brachytherapy at the British Columbia Cancer Agency. Baseline patient, treatment, and implant factors were recorded prospectively. Acute urinary toxicity data were prospectively recorded at baseline and each follow-up visit. Patients with ≥2 years of follow-up data were grouped into cohorts of 500 for analysis. Two thousand eleven patients met the above criteria. Acute urinary retention (AUR) in the acute period (within 6 months of implant) occurred in 9.1% of patients overall and was prolonged (catheterization >20 days) in 3.4%. Both overall AUR and prolonged AUR decreased across implant cohorts (p ≤ 0.001 in both cases). Overall acute Radiation Therapy Oncology Group (RTOG) Grades 0 and 1 urinary toxicity rate was 57.5% and RTOG Grades 2 and 3 urinary toxicity rates were 34.3% and 8.1%, respectively. Acute toxicity improved over time for both RTOG Grades ≥2 and ≥3 toxicity (p < 0.0001). International prostate symptom score resolution to baseline was achieved in 80.5% of patients with a median time of 12.2 months. Acute AUR and RTOG urinary toxicity rates continue to decline with the increasing experience of our provincial prostate brachytherapy program, despite its expansion to new centers and addition of members. This is likely due to better patient selection, refinement in treatment planning and implantation technique, and mentorship and training process.

Predicting the Severity of Acute Urinary Toxicity after Brachytherapy with Iodine-125 for Localized Prostate Cancer

Prostate cancer is one of the common cancers in the world. In Japan, prostate brachytherapy (PB) with iodine-125 has become a treatment option for localized prostate cancer since 2003. Nevertheless, severe acute urinary toxicity (AUT) remains as one of the intractable side effects. We assessed AUT and the changes in international prostate symptom score (IPSS) before and after PB for localized prostate cancer. IPSS is a questionnaire tool for tracking the subjective urinary symptoms. Between 2006 and 2009, 104 eligible patients underwent PB with iodine-125 were analyzed. AUT was graded with the radiation therapy oncology group (RTOG) scale. Eligible patients filled out IPSS questionnaires before and after PB. Clinical and treatment-related factors were examined for correlation with the severity of AUT and the interval to IPSS resolution. AUT of RTOG Grade 0 (no changes) and Grade 2 was detected in one and 96 patients, respectively, whereas seven patients (6.7%) experienced AUT of Grade 3. Thus, the incidence of severe AUT (Grade 3) after PB was low. A greater number of needles (p = 0.012) were associated with AUT of RTOG Grade 3 on the univariate analysis. The median interval to IPSS resolution was 6 months (7 ± 6 months). Greater post-implant maximal IPSS (p < 0.001) was associated with slower IPSS resolution, whereas higher pre-implant IPSS (p < 0.001) was associated with faster IPSS resolution on the multivariate analysis. In conclusion, reducing the number of needles in PB may be helpful for decreasing the rate of severe AUT.

Development of Late Toxicity and International Prostate Symptom Score Resolution After External-Beam Radiotherapy Combined With Pulsed Dose Rate Brachytherapy for Prostate Cancer

To investigate the development of gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, erectile dysfunction, and International Prostate Symptom Score (IPSS) resolution in a cohort of patients treated with external-beam radiotherapy (EBRT) followed by a brachytherapy pulsed dose rate (PDR) boost. Between 2002 and 2008, 110 patients were treated with 46-Gy EBRT followed by PDR brachytherapy (24.96-28.80 Gy). The investigated outcome variables, GI toxicity, GU toxicity, erectile dysfunction, and IPSS were prospectively scored at several time points during follow-up. Association between time (as continuous and categorical variable) and the outcome variables was assessed using generalized linear models. No statistically significant association was found between time (continuous) and GI toxicity (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.89-1.06), GU toxicity (OR, 0.97; 95% CI, 0.91-1.03), erectile dysfunction (OR, 1.06; 95% CI, 0.99-1.11), and IPSS (-0.11; 95% CI, -0.41-0.20). Also, no statistically significant association was found between these variables and time as a categorical variable. GU toxicity was associated with IPSS resolution (OR, 1.16; 95% CI, 1.09-1.24). Posttreatment IPSS was associated with pretreatment IPSS (0.52; 95% CI, 0.25-0.79). No accumulation of high-grade toxicity over time could be established for a group of patients treated with EBRT and PDR brachytherapy for prostate cancer, probably because high-grade late toxicity resolves with time. Also, differences in IPSS values among patients are smaller after treatment than before treatment.

Permanent Prostate Brachytherapy in Prostate Glands

<h3>Purpose</h3> To investigate the dosimetry, treatment-related morbidity, and biochemical outcomes for brachytherapy in patients with prostate glands <20 cm³. <h3>Methods and Materials</h3> From November 1996 to October 2006, 104 patients with prostate glands <20 cm³ underwent brachytherapy. Multiple prostate, urethral, and rectal dosimetric parameters were evaluated. Treatment-related urinary and rectal morbidity were assessed from patient questionnaires. Cause-specific survival, biochemical progression-free survival, and overall survival were recorded. <h3>Results</h3> The median patient age, follow up, and pre-treatment ultrasound volume was 64 years, 5.0 years and 17.6cm³, respectively. Median day 0 dosimetry was significant for the following: V100 98.5%, D90 126.1% and R100 <0.5% of prescription dose. The mean urethral and maximum urethral doses were 119.6% and 133.8% of prescription. The median time to International Prostate Symptom Score resolution was 4 months. There were no RTOG grade III or IV rectal complications. The cause-specific survival, biochemical progression-free survival, and overall survival rates were 100%, 92.5%, and 77.8% at 9 years. For biochemically disease-free patients, the median most recent postbrachytherapy PSA value was 0.02 ng/mL. <h3>Conclusion</h3> Our results demonstrate that brachytherapy for small prostate glands is highly effective, with an acceptable morbidity profile, excellent postimplant dosimetry, acceptable treatment-related morbidity, and favorable biochemical outcomes.

Predictive Factors for Acute and Late Urinary Toxicity After Permanent Prostate Brachytherapy: Long-Term Outcome in 712 Consecutive Patients

To describe the frequency of acute and late Radiation Therapy Oncology Group (RTOG) urinary toxicity, associated predictive factors, and resolution of International Prostate Symptom Score (IPSS) in 712 consecutive prostate brachytherapy patients. Patients underwent implantation between 1998 and 2003 (median follow-up, 57 months). The IPSS and RTOG toxicity data were prospectively collected. The patient, treatment, and implant factors were examined for an association with urinary toxicity. The time to IPSS resolution was examined using Kaplan-Meier curves, and multivariate modeling of IPSS resolution was done using Cox proportional hazards regression analysis. Logistic regression analysis was used to examine the factors associated with urinary toxicity. The IPSS returned to baseline at a median of 12.6 months. On multivariate analysis, patients with a high baseline IPSS had a quicker resolution of their IPSS. Higher prostate D90 (dose covering 90% of the prostate), maximal postimplant IPSS, and urinary retention slowed the IPSS resolution time. The rate of the actuarial 5-year late urinary (>12 months) RTOG Grade 0, 1, 2, 3, and 4 was 32%, 36%, 24%, 6.2%, and 0.1%, respectively. At 7 years, the prevalence of RTOG Grade 0-1 was 92.5%. Patients with a larger prostate volume, greater number of needles, greater baseline IPSS, and use of hormonal therapy had more acute toxicity. On multivariate analysis, the significant predictors for late greater than or equal to RTOG toxicity 2 were a greater baseline IPSS, maximal postimplant IPSS, presence of acute toxicity, and higher prostate V150 (volume of the prostate covered by 150% of the dose). More recently implanted patients had less acute urinary toxicity and patients given hormonal therapy had less late urinary toxicity (all p < 0.02). Most urinary symptoms resolved within 12 months after prostate brachytherapy, and significant long-term urinary toxicity was very low. Refined patient selection and greater technical experience in prostate brachytherapy were associated with less urinary toxicity.

Biochemical and Functional Outcomes Following Brachytherapy With or Without Supplemental Therapies in Men ≤50 Years of Age With Clinically Organ-Confined Prostate Cancer

Despite favorable long-term prostate brachytherapy outcomes, there remains a bias to recommend radical prostatectomy for young patients. Herein, we report cause-specific survival, biochemical progression-free survival (bPFS), overall survival and functional outcomes in men < or =50 years of age who underwent brachytherapy with or without supplemental therapies. From October 1995 to November 2004, 42 consecutive patients < or =50 years of age underwent permanent interstitial brachytherapy. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The mean and median follow-up was 5.6 and 5.1 year. bPFS was defined as a prostate-specific antigen < or =0.40 ng/mL after nadir. Functional outcome determinations included urinary, bowel and erectile function evaluations. Multiple clinical, treatment and dosimetric parameters were evaluated for impact on survival. Cause-specific survival, bPFS, and overall survival for the entire cohort were 100%, 97.7%, and 100%, respectively. To date, only one patient has failed biochemically. Median time to International Prostate Symptom Score resolution was 3 months. No patient required a postimplant transurethral resection of the prostate or developed urinary incontinence. Two patients developed bulbomembtranous urethral strictures. The overall potency preservation rate was 75.6% (International Index of Erectile Function-6 >13 without mechanical or pharmacologic support). Bowel habits were reported to be the same or better than prior to treatment in 92.5% patients. No severe rectal complications requiring therapeutic intervention occurred. Men < or =50 years of age have favorable biochemical and functional outcomes following brachytherapy. Depending on risk group assignment, brachytherapy with or without supplemental therapies should be considered a viable option for all healthy men regardless of age.

Role of Trospium Chloride in Brachytherapy-Related Detrusor Overactivity

After prostate brachytherapy, pronounced urinary irritative symptomatology occurs in a substantial minority of patients. In this study, we evaluated the impact of trospium chloride in prostate brachytherapy patients with symptoms consistent with an overactive bladder (OAB). From January 1999 through December 2005, 69 permanent prostate brachytherapy patients were identified who received trospium as first-line treatment for OAB. The median interval from implant to initiation of trospium was 23.4 months. Before trospium, we obtained a postvoid residual urine assessment (PVR) and International Prostate Symptom Score (IPSS) for all patients. IPSS resolution was defined as a return to within 2 points of the pre-brachytherapy value and individual IPSS question resolution was defined by a decrease of at least 1 point. The mean patient age was 66.0 years, with a pre-brachytherapy prostate volume of 31.0 cm(3) and a mean preimplant IPSS of 6.5. At trospium initiation, the mean IPSS was 9.6 with a mean PVR of 12.3 mL. IPSS normalization was documented in 55 (79.7%) patients. Twelve months after trospium initiation, the IPSS had decreased by a mean of 4.3 points with the improvement most pronounced for urgency. After trospium, no clinically significant differences were noted in the mean PVR. Twenty-two patients discontinued trospium as a result of the absence of a clinical response or pharmacologic side effects, or after complete resolution of symptoms. Nearly 80% of patients with brachytherapy-related detrusor overactivity responded favorably to trospium with improvements in IPSS (especially urgency). This was accomplished with an acceptable morbidity profile.

Severity categories of the International Prostate Symptom Score before, and urinary morbidity after, permanent prostate brachytherapy

To determine if the International Prostate Symptom Score (IPSS) before seed implantation, stratified into mild (0-7), moderate (8-19) and severe (>20) categories, predicts brachytherapy-related morbidity in terms of IPSS resolution, catheter dependency and the need for surgical intervention after brachytherapy. From January 1998 to September 2003, 1034 consecutive patients had permanent interstitial brachytherapy for clinical stage T1b-T3a NXM0 (2002 system) prostate cancer. Of the 1034 patients, 739 (71.5%) presented with an IPSS of 0-7, 287 (27.7%) of 8-19, and eight (0.8%) of > or = 20. The IPSS 8-19 cohort was further stratified into 8-14 (237 men) and 15-19 (50 men) subgroups. The median follow-up was 38.2 months. In all patients, an alpha-blocker was initiated before brachytherapy and continued at least until the IPSS normalized, the latter defined as a return to within 1 point of that before implantation. A median of 21 IPSS questionnaires were obtained per patient. Several clinical, treatment and dosimetric variables were evaluated as predictors of urinary morbidity. For the entire cohort, the IPSS peaked at a mean of 0.5 months after implantation and resolved at a mean of 1.7 months. At 5 years after brachytherapy, 90.1% of patients at risk (88.8%, 95.5%, and four of eight patients with a pre-implant IPSS of 0-7, 8-19 and > or = 20, respectively) were within the IPSS 0-7 category. Compared to the pre-implant IPSS, 13 patients (8%) were assigned to a higher IPSS severity category. Neither prolonged urinary catheter dependency (>5 days; 16 patients, 1.5%) or transurethral resection of the prostate (TURP, 17 patients, 1.6%) depended on the pre-implant IPSS subgroup. In Cox regression analysis, IPSS resolution was best predicted by pre-implant IPSS, prolonged catheter dependency by patient age, and TURP by any catheter dependency, the maximum IPSS increase and the maximum urethral dose. The IPSS before implantation predicted the resolution of IPSS after brachytherapy, but did not correlate with substantial urinary morbidity, including catheter dependency or the need for TURP. At 5 years after brachytherapy, 90.1% of patients at risk were assigned to the IPSS 0-7 category.

Selecting patients with pretreatment postvoid residual urine volume less than 100 mL may favorably influence brachytherapy-related urinary morbidity

ObjectivesTo evaluate the relationship between pretreatment postvoid residual urine (PVR) less than 100 mL and brachytherapy-related urinary morbidity. MethodsA total of 204 patients with a pretreatment PVR measurement underwent permanent prostate brachytherapy with urethral-sparing techniques (100% to 140% minimal peripheral dose) for clinical Stage T1b–T2c (2002 American Joint Committee on Cancer staging system) prostate cancer. The median follow-up was 11.7 months. Evaluation of urinary morbidity consisted of the time to International Prostate Symptom Score (IPSS) resolution, length of catheter dependency, and the need for postimplant surgical intervention. IPSS resolution was defined as a return to within 1 point of the score at baseline. In all patients, an alpha-blocker was initiated before implantation and continued at least until the IPSS returned to baseline. Statistically significant predictors of urinary morbidity were determined using Cox regression analysis of multiple clinical, treatment, and dosimetric parameters. ResultsFor the entire cohort, the mean time to IPSS resolution was 2.5 months. The urinary catheter was removed on the day of implantation in 171 patients (83.8%), with no patient remaining catheter dependent for more than 3 days. To date, no patient has required postimplant surgical intervention. On multivariate analysis, pretreatment PVR predicted for clinically irrelevant differences in IPSS resolution and did not influence catheter dependency. ConclusionsThe selection of patients with a pretreatment PVR of less than 100 mL was associated with rapid IPSS resolution, the absence of prolonged (more than 3 days) catheter dependency, and the elimination of postbrachytherapy surgical intervention for bladder outlet obstruction.

The influence of isotope and prostate volume on urinary morbidity after prostate brachytherapy

To evaluate the influence of isotope and prostate size on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after prostate brachytherapy. Between January 1998 and June 2003, 976 consecutive patients underwent brachytherapy for clinical stage T1b-T3a (2002 American Joint Committee on Cancer) prostate cancer. Seven hundred eighty-nine (80.8%) were implanted with 103Pd and 187 (19.2%) with 125I. The median follow-up was 41.2 months. Patients were stratified into size cohorts < or = 25 cm3, 25.1-35 cm3, 35.1-45 cm3, and >45 cm3. Four hundred eighteen patients (42.8%) received androgen deprivation therapy (ADT). Four hundred eighty-six patients (49.7%) received supplemental external-beam radiation therapy (XRT). In all patients, an alpha blocker was initiated before implantation and continued at least until the IPSS returned to baseline. IPSS resolution was defined as a return to within one point of baseline. The median number of IPSS determinations per patient was 21. Clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment PSA, Gleason score, clinical T stage, percent positive biopsies, preimplant IPSS, ultrasound volume, planning volume, isotope, V(100/150/200), D(90), urethral dose (average and maximum), supplemental XRT, ADT, and the duration of ADT (< or = 6 months vs. >6 months). Catheter dependency and the need for postsurgical intervention were also evaluated. For both isotopes and all prostate size cohorts, IPSS peaked 1 month after implantation and returned to baseline at a mean of 1.9 months. Stratification of prostate size cohorts by isotope demonstrated no significant differences in prolonged catheter dependency (> or = 5 days), IPSS resolution, or postimplant surgical intervention. In Cox regression analysis, IPSS normalization was best predicted by preimplant IPSS, XRT, and any need for a catheter after brachytherapy. Catheter dependency correlated with prostate size and ADT, whereas the need for surgical intervention was most closely related to any catheter dependency, maximum urethral dose, ADT, and maximum IPSS increase. Regardless of prostate size, isotope did not impact IPSS resolution, catheter dependency, or the need for postbrachytherapy surgical intervention. Although prostate size did predict for short-term (<5 days) catheter dependency, it did not influence IPSS resolution or the need for surgical intervention.

Influence of Preimplant International Prostate Symptom Score on Urinary Morbidity Following Prostate Brachytherapy

Purpose/Objective: To determine if the preimplant International Prostate Symptom Score (IPSS), stratified into mild (0–7), moderate (8–19), and severe (> 20) categories, predicts for brachytherapy-related morbidity in terms of IPSS resolution, catheter dependency and the need for postbrachytherapy surgical intervention.

SU‐FF‐T‐27: Detailed Urethral Dosimetry in the Evaluation of Prostate Brachytherapy‐Related Urinary Morbidity

Purpose: To evaluate the relationship between post‐prostate brachytherapy urinary morbidity and urethral doses calculated at the base, mid‐prostate, apex and urogenital diaphragm. Method and Materials: 186 consecutive patients with no history of transurethral resection underwent monotherapeutic prostate brachytherapy (no external beam radiation or androgen deprivation) with urethral sparing techniques (average urethral dose 100–140% of prescribed dose). The median follow‐up was 45.5 months. Urinary morbidity was defined by time to International Prostate Symptom Score (IPSS) resolution, maximum increase in IPSS, catheter dependency, and the need for postimplant surgical intervention. An α‐blocker was initiated approximately 2 weeks prior to implantation and continued until the IPSS returned to baseline. Evaluated parameters included overall urethral dose, doses to the base, mid‐prostate, apex and urogenital diaphragm, patient age, clinical T‐stage, preimplant IPSS, ultrasound volume, isotope, D90 and V100/150/200. Results: Of the 186 patients, 176 had the urinary catheter permanently removed on the day zero and only 1 patient required a urinary catheter &gt; 5 days. No patient developed a urethral stricture, and only two patients required a postbrachytherapy TURP. For the entire cohort, mean IPSS peaked 2 weeks following implantation, and the median time to IPSS resolution of 3 weeks. For the entire cohort, only isotope predicted for IPSS resolution, while neither overall average prostatic urethra nor segmental urethral dose predicted for IPSS resolution. The maximum postimplant IPSS increase was best predicted by preimplant IPSS and the maximum apical urethral dose. Conclusion: With the use of prophylactic α‐blockers and adherence to urethral sparing techniques, urethral dosimetry did not improve the ability to predict urinary morbidity. Neither the average dose to the prostatic urethra nor urethral doses stratified into base, mid‐prostate, apex, and urogenital diaphragm segments predicted for IPSS normalization. Radiation doses of 100–140% mPD are well tolerated by all segments of the prostatic urethra.

SU‐FF‐T‐51: Relationship Between Isotope, Prostate Volume and Urinary Morbidity Following Prostate Brachytherapy

Purpose: To evaluate the influence of isotope and prostate size on International Prostate Symptom Score (IPSS) normalization, catheter dependency and the need for surgical intervention following permanent prostate brachytherapy. Method and Materials: 976 consecutive patients underwent permanent brachytherapy for clinical stage T1b‐T3a prostate cancer. Of these, 789 were implanted with Pd‐103 and 187 with I‐125. Patients were stratified into size cohorts ⩽ 25.0 cm3, 25–35 cm3, 35–45 cm3, and &gt; 45.0 cm3. 418 received androgen deprivation therapy (ADT). 486 received supplemental external beam radiation therapy (XRT). In all patients, an α‐blocker was initiated prior to implantation and continued until the IPSS returned to baseline. The median number of IPSS determinations per patient was 21. Clinical, treatment and dosimetric parameters evaluated included patient age, pretreatment PSA, Gleason score, clinical T‐stage, percent positive biopsies, preimplant IPSS, ultrasound volume, planning volume, isotope, V100/150/200, D90, urethral dose, supplemental XRT, ADT, and the duration of ADT (⩽ 6 months versus &gt; 6 months). Results: For both isotopes and all size cohorts, IPSS peaked 1 month following implantation and returned to baseline at a mean of 1.9 months. Stratification of prostate size cohorts by isotope resulted in no significant differences in prolonged catheter dependency, IPSS resolution or postimplant surgical intervention. In Cox regression analysis, IPSS normalization was best predicted by preimplant IPSS, XRT and any need for a catheter following brachytherapy. Catheter dependency correlated with prostate volume, while the need for surgical intervention was related to catheter dependency, maximum urethral dose, ADT and maximum IPSS increase. Conclusion: When stratified by prostate size, the choice of isotope did not impact IPSS resolution, catheter dependency or the need for postbrachytherapy surgical intervention. While prostate size did predict for short‐term (&lt; 5 day) catheter dependency, it did not influence IPSS resolution or the need for surgical intervention.

Detailed urethral dosimetry in the evaluation of prostate brachytherapy-related urinary morbidity

To evaluate the relationship between urinary morbidity after prostate brachytherapy and urethral doses calculated at the base, midprostate, apex, and urogenital diaphragm. From February 1998 through July 2002, 186 consecutive patients without a prior history of a transurethral resection underwent monotherapeutic brachytherapy (no supplemental external beam radiation therapy or androgen deprivation therapy) with urethral-sparing techniques (average urethral dose 100%-140% minimum peripheral dose) for clinical T1c-T2b (2002 AJCC) prostate cancer. The median follow-up was 45.5 months. Urinary morbidity was defined by time to International Prostate Symptom Score (IPSS) resolution, maximum increase in IPSS, catheter dependency, and the need for postimplant surgical intervention. An alpha blocker was initiated approximately 2 weeks before implantation and continued at least until the IPSS returned to baseline. Evaluated parameters included overall urethral dose (average and maximum), doses to the base, midprostate, apex, and urogenital diaphragm, patient age, clinical T stage, preimplant IPSS, ultrasound volume, isotope, and D90 and V100/150/200. Of the 186 patients, 176 (94.6%) had the urinary catheter permanently removed on the day of implantation with only 1 patient requiring a urinary catheter >5 days. No patient had a urethral stricture and only 2 patients (1.1%) required a postbrachytherapy transurethral resection of the prostate (TURP). For the entire cohort, IPSS on average peaked 2 weeks after implantation with a mean and median time to IPSS resolution of 14 and 3 weeks, respectively. For the entire cohort, only isotope predicted for IPSS resolution, while neither overall average prostatic urethra nor segmental urethral dose predicted for IPSS resolution. The maximum postimplant IPSS increase was best predicted by preimplant IPSS and the maximum apical urethral dose. With the routine use of prophylactic alpha blockers and strict adherence to urethral-sparing techniques, detailed urethral dosimetry did not substantially improve the ability to predict urinary morbidity. Neither the average dose to the prostatic urethra nor urethral doses stratified into base, midprostate, apex, or urogenital diaphragm segments predicted for IPSS normalization. Radiation doses of 100%-140% minimum peripheral dose are well tolerated by all segments of the prostatic urethra with resultant tumoricidal doses to foci of periurethral cancer.

The impact of radiation dose to the urethra on brachytherapy-related dysuria

Purpose To determine the effect of urethral dose on dysuria after permanent prostate brachytherapy. Methods and materials One hundred eight patients without a preimplant history of a transurethral resection underwent brachytherapy on one of two prospective randomized trials for clinical T1c–T2c (2002 AJCC) prostate cancer. Urethral dose was stratified into cohorts of <150% and ⩾150% minimum peripheral dose (mPD) respectively. No patient received prophylactic alpha blockers. The median follow-up was 27.4 months. Dysuria was defined as pain and/or burning on urination and was evaluated on a 0–10 scale. Normalization of dysuria was defined as a return to within 1 point of baseline. Dysuria surveys were obtained before brachytherapy and at 1, 3, 6, and 12 months after implantation. Clinical, treatment, and dosimetric parameters evaluated included urethral dose, age, preimplant International Prostate Symptom Score (I-PSS), ultrasound volume, hormonal status, supplemental XRT, isotope, V 100/200, D 90, the maximum post-implant I-PSS, and the time to I-PSS resolution. Results The incidence of dysuria peaked at 85% one month after brachytherapy with subsequent resolution over time. Radiation dose to the urethra (stratified into cohorts of <150%, and ⩾150% mPD) was not a significant predictor of prevalence, severity, or resolution of dysuria. In a multivariate analysis, isotope predicted for dysuria normalization while preimplant I-PSS and D 90 predicted for maximum dysuria; however, the area under the ROC curve and the Pearson correlation coefficient revealed weak correlations. Conclusions Dysuria is common after brachytherapy, but typically minimal in severity. Urethral doses did not predict for either dysuria severity or normalization. Although preimplant I-PSS was the strongest predictor of maximum dysuria and isotope the best predictor for dysuria normalization, robust predictors for brachytherapy-related dysuria were not identified.

Androgen deprivation–induced changes in prostate anatomy predict urinary morbidity after permanent interstitial brachytherapy

Purpose To evaluate the cytoreductive consequences of neoadjuvant androgen deprivation therapy on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after permanent interstitial brachytherapy. Methods and materials A total of 116 patients (median follow-up, 30 months) with preandrogen and postandrogen deprivation therapy ultrasound studies and no history of preimplant transurethral resection of the prostate were evaluated. Androgen deprivation–induced changes in prostate volume, transition zone (TZ) volume, and urethral location were correlated with IPSS resolution, catheter dependency, and the need for postimplant surgical intervention. Prostate gland and TZ dimensions and volumes were measured by prolate ellipsoid calculation from the static ultrasound images. The urethral location was determined by identification of a urinary catheter. Additional clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment prostate-specific antigen, Gleason score, clinical T stage, preimplant IPSS, pre- and postandrogen deprivation ultrasound studies, treatment planning volume, supplemental external beam RT, isotope, total implant activity, Day 0 maximal dose received by 90% of the prostate gland, Day 0 percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose, and urethral dose. Results For hormonally manipulated patients, the prostate volume at implantation did not have a statistical influence on the percentage of patients returning to IPSS baseline, the time for IPSS normalization, the incidence of catheter dependency, the catheter-dependency time, or the need for postimplant surgical intervention. However, when compared with the hormone-naive cohort, hormonally manipulated patients were more likely to undergo postimplant surgical intervention (5.2% vs. 0.3%, p = 0.001). Greater androgen deprivation–induced reductions in prostate and TZ volumes, along with movement of the urethra closer to the posterior border of the prostate gland, resulted in a decreased incidence of postimplant urinary morbidity. Using Cox regression analysis, the time to IPSS resolution was best predicted by the percentage of TZ volume reduction. Stepwise linear regression analysis demonstrated that the catheter-dependency time was best predicted by the prehormonal therapy prostate volume, posthormonal therapy TZ volume, and the change in the urethral position; prolonged catheter dependency by the percentage of TZ volume reduction, prehormonal therapy TZ index, and the change in the urethral position; and the need for postimplant surgical intervention by the posthormonal therapy TZ index and the change in the urethral location. Conclusion After neoadjuvant androgen deprivation therapy for volume reduction, some brachytherapy-related urinary morbidity parameters are highly related to the preandrogen deprivation prostate volume, variants in the TZ volume, and changes in the urethral location.