Treatment outcomes with permanent brachytherapy in high-risk prostate cancer patients stratified into prognostic categories.

PURPOSE: To determine whether a previously reported substratification system can be extrapolated to patients with high-risk prostate cancer treated with permanent interstitial brachytherapy. METHODS AND MATERIALS: Four hundred six National Comprehensive Cancer Network patients with high-risk prostate cancer treated with permanent prostate brachytherapy with or without supplemental external beam radiotherapy were stratified into good (prostate-specific antigen >20 or Gleason score ≥8 or ≥T3), intermediate (prostate-specific antigen >20 and ≥T3), and poor (Gleason score ≥8 with ≥1 additional high-risk feature) prognostic cohorts. Because of only 1 patient with intermediate high-risk disease, the analysis was performed on patients in the good and poor cohorts. Biochemical failure (BF), prostate cancer-specific mortality (PCSM), distant metastasis, and overall mortality were assessed as function of prognostic group. Multiple parameters were evaluated for impact on outcome. RESULTS: With a median followup time of 7.9 years, 10- and 14-year rates of BF and PCSM for the entire cohort were 7.8% and 3.7%, respectively. The BF rate was significantly greater in the poor prognostic category (16.8% vs. 7.8%, p = 0.041). The poor prognostic category was the strongest predictor of BF in univariate and multivariate analyses. No statistically significant differences in PCSM, distant metastasis, or overall mortality were identified between the good and poor prognostic categories. CONCLUSIONS: Patients with high-risk prostate cancer treated with a brachytherapy approach have excellent long-term biochemical control and cancer-specific survival. The poor prognostic high-risk category had a higher rate of BF compared with the good prognostic category without a higher rate of PCSM or distant metastasis.

Relationship between the transition zone index of the prostate gland and urinary morbidity after brachytherapy.

OBJECTIVES: To evaluate whether urinary symptomatology after prostate brachytherapy is related to the preimplant transition zone index (TZI = transition zone volume/prostate gland volume). METHODS: A total of 170 consecutive patients without a prior history of transurethral resection of the prostate gland (TURP) underwent transperineal ultrasound-guided prostate brachytherapy for clinical T1c-T3a carcinoma of the prostate gland. Prostate gland and transition zone dimensions and volumes were measured by prolate ellipsoid calculation from the static ultrasound images. The relationship between TZI and various measures of urinary dysfunction including normalization of International Prostate Symptom Scores (IPSS), catheter dependency, the need for a subsequent TURP, and the duration of alpha-blocker dependency were evaluated. Additional clinical parameters evaluated included the relationship between TZI and patient age, clinical T stage, prostate ultrasound volume, neoadjuvant hormonal manipulation, and preimplant IPSS. For all indices of urinary dysfunction other than serial IPSS, the median patient follow-up was 89.3 weeks. The median follow-up for serial IPSS evaluations was 37.3 weeks with a mean of 11.2 questionnaires per patient. RESULTS: The mean TZI for the 170 patients was 0.23 +/- 0.06 (prostate gland volume 30.3 +/- 8.7 cm(3), transition zone volume 7.3 +/- 3.6 cm(3)). The TZI correlated with the time for IPSS normalization, the maximum IPSS after brachytherapy, and the maximum increase in IPSS. Conversely, the TZI did not correlate with either catheter dependency or alpha-blocker dependency. Two of 170 patients (1.2%) required a postimplant TURP. The TZI in these 2 patients (0.34) was statistically different (P = 0.016) from the mean. CONCLUSIONS: In prostate brachytherapy patients, the preimplant TZI predicted the need for a subsequent transurethral resection. The TZI also correlated with multiple variants of IPSS. Conversely, TZI did not correlate with either catheter dependency or alpha-blocker dependency.

Comparison of dose length, area, and volume histograms as quantifiers of urethral dose in prostate brachytherapy.

PURPOSE: To determine the magnitude of the differences between urethral dose-volume, dose-area, and dose-length histograms (DVH, DAH, and DLH, respectively, or DgH generically). METHODS AND MATERIALS: Six consecutive iodine-125 ((125)I) patients and 6 consecutive palladium-103 ((103)Pd) patients implanted via a modified uniform planning approach were evaluated with day 0 computed tomography (CT)-based dosimetry. The urethra was identified by the presence of a urinary catheter and was hand drawn on the CT images with a mean radius of 3.3 +/- 0.7 mm. A 0.1-mm calculation matrix was employed for the urethral volume and surface analysis, and urethral dose points were placed at the centroid of the urethra on each 5-mm CT slice. RESULTS: Although individual patient DLHs were step-like, due to the sparseness of the data points, the composite urethral DLH, DAH, and DVHs were qualitatively similar. The DAH curve delivered more radiation than the other two curves at all doses greater than 90% of the prescribed minimum peripheral dose (mPD) to the prostate. In addition, the DVH curve was consistently higher than the DLH curve at most points throughout that range. Differences between the DgH curves were analyzed by integrating the difference curves between 0 and 200% of the mPD. The area-length, area-volume, and volume-length difference curves integrated in the ratio of 3:2:1. The differences were most pronounced near the inflection point of the DgH curves with mean A(125), V(125), and L(125) values of 36.6%, 31.4%, and 23.0%, respectively, of the urethra. Quantifiers of urethral hot spots such as D(10), defined as the minimal dose delivered to the hottest 10% of the urethra, followed the same ranking: area analysis indicated the highest dose and length analysis, the lowest dose. D(10) was 148% and 136% of mPD for area and length evaluations, respectively. Comparing the two isotopes in terms of the amount of urethra receiving a given dose, (103)Pd implants were significantly cooler than (125)I implants over most of the range of clinical interest, from 100% to 150% of mPD. CONCLUSION: Dose gradients in prostate implants result in the observed ordering of DAH, DVH, and DLH from higher to lower doses. The three histogram approaches remain in close agreement up to 100% of the mPD but diverge at higher doses. Although urethral point doses are the most easily determined, they underestimate the amount of urethra at risk at higher doses compared to dose area analysis. Because dosimetric parameters detailing high-dose regions such as D(10) show only slight differences between calculation methods, they are recommended over the corresponding geometric entities G(150) or G(175). The differences between the D(gg) entities are sufficiently small that they are unlikely to be of clinical significance or to confound analyses attempting to correlate urinary morbidity with urethral dosimetry.

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.

The effect of constipation on rectal dosimetry following prostate brachytherapy.

The purpose of this study is to report the effect of dilatation of the anorectum on rectal dosimetry following an 125I prostate implant. Three months following prostate brachytherapy, 2 computed tomography (CT) scans of the prostate gland were obtained within 90 minutes of each other. The first CT scan revealed a dilated anorectum secondary to constipation. The second CT was obtained following the administration of an enema with a successfully evacuated rectum. Differences in radiation doses to the distended and empty rectum were computed via the mean dose, the maximum dose per slice, the distance from the base, and in terms of the surface of the anterior quadrant of the rectum receiving 100%, 125%, 150%, 175%, 200%, and 250% of the prescribed dose. The dose to the rectal wall was substantially increased in the distended state for all evaluated parameters. In general, the mean dose to the rectal wall was increased by a factor of 1.5 in the distended state. In both scenarios, the dose to the rectal wall peaked near midgland. In terms of 10 degrees rectal wall sectors receiving a given percentage of the prescribed minimal peripheral dose, S%mPD, the S100, S125, S150, S175, S200, and S250 were substantially greater for the distended versus the empty rectum. The magnitude of the percentage difference in dose between the distended and evacuated rectum increased with dose level while the difference in the number of sectors receiving a given dose level was greatest at 125% and 150% of the prescribed dose. We recommend detailed postimplant attention to bowel habits for at least 2 half-lives of the implanted isotope to minimize rectal distention, decrease radiation dose to the anterior rectal wall, and subsequently minimize potential constipation related rectal toxicity.