[Show abstract][Hide abstract] ABSTRACT: To determine whether adverse pathologic features, including tumor grade and percent positive biopsy (PPB) cores, predict for prostate size reduction after neoadjuvant cytoreductive therapy.
Eighty-two consecutive patients who were diagnosed with prostate cancer by transperineal template-guided mapping biopsy (TTMB) received neoadjuvant cytoreductive therapy. The median number of biopsy cores was 59. Thirty patients received a leutinizing hormone-releasing hormone agonist and bicalutamide, whereas 52 patients received bicalutamide (50mg daily) and dutasteride (0.5mg daily). A transrectal ultrasound volumetric study of the prostate gland and ellipsoid volume determinations of the prostate gland and transition zone (TZ) were obtained immediately before TTMB and at 90 days (±7 days) after the initiation of neoadjuvant medical therapy. Univariate and multivariate regression analyses were performed to identify predictors of prostate gland and TZ volume reduction.
At TTMB, the mean prostate volumetric and ellipsoid volumes were 55.4 cm(3) and 49.0 cm(3), respectively. After neoadjuvant medical therapy, the mean volumetric and ellipsoid prostate volumes were 30.8 cm(3) and 28.5 cm(3), respectively. On average, the prostate volume decreased by 43.9% and 41.0% on volumetric and ellipsoid measurements, respectively. The TZ volume decreased from 19.8 cm(3) to 10.1 cm(3) (mean volume reduction of 47.7%). In multivariate analysis, prostate volume cytoreduction was most closely associated with PPB (p=0.014), TTMB prostate volume (p=0.01), and drug regimen (p=0.001).
The degree of prostate volume cytoreduction was positively associated with higher Gleason score and PPBs. Greater reductions in prostate volume may be an indicator of more aggressive cancer.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of prostate-specific antigen (PSA) velocity (PSAV) on prostate cancer diagnosis, Gleason score, tumor location, and cancer volume in men undergoing transperineal template-guided mapping biopsy (TTMB). PSAV has been associated with greater Gleason scores and greater prostate cancer-specific mortality.
From January 2005 through September 2007, 217 patients underwent TTMB. The inclusion criteria included a persistently elevated PSA level and/or diagnosis of atypical small acinar proliferation or high-grade prostatic intraepithelial neoplasia on previous biopsy. The prostate gland was arbitrarily divided into 24 regions, and a median of 58 cores were obtained per patient. The patients were divided into 3 velocity cohorts according to the following changes in PSA level in the year before biopsy: < or =0.0, 0.1-1.9, and > or =2.0 ng/mL. The PSAV was evaluated as a predictor for prostate cancer diagnosis, Gleason score, tumor volume, and cancer location.
The mean patient age was 64.2 years, with a mean prebiopsy PSA level of 8.5 ng/mL. Prostate cancer was diagnosed in 97 patients (44.7%). The study population had undergone an average of 1.8 +/- 1.0 biopsies before TTMB. PSAV did not predict for prostate cancer diagnosis (P = .84), Gleason score (P = .78), the percentage of positive cores (P = .37), or tumor location.
Among patients with persistently elevated PSA levels despite previously negative biopsy findings, PSAV did not reliably predict for a diagnosis of prostate cancer nor did it correlate with prostate cancer grade, volume, or location using TTMB.
[Show abstract][Hide abstract] ABSTRACT: Recent studies have suggested that extracapsular brachytherapy treatment margins correlate with biochemical control. It is likely that volumetric geographic dosimetric parameters will be more robust than selected radial measurements. Accordingly, we evaluated extracapsular volumetric dosimetric parameters in low-risk patients.
A total of 263 low-risk prostate cancer patients randomized to Pd-103 versus I-125 were implanted with a brachytherapy target volume consisting of the prostate with a 5-mm periprostatic margin. The median follow-up was 4.2 years. All patients were implanted at least 3 years prior to analysis. Within 2 hours of implantation, an axial CT was obtained for postimplant dosimetry. A 5-mm three-dimensional periprostatic anulus was constructed around the prostate and evaluated in its entirety and in 90 degrees segments. Prostate and anular dosimetric parameters consisted of V100/V150/V200 and D90. Biochemical progression-free survival (bPFS) was defined as a PSA < or =0.50 ng/mL after nadir.
The Pd-103 and I-125 arms were well-matched in terms of clinical, biochemical, and pathologic presentation. Six-year bPFS was 96.8% versus 99.2% for I-125 versus Pd-103 (P = 0.149). The most recent median posttreatment PSA was <0.04 ng/mL for both isotopes. No significant differences in postoperative anular doses were discerned between bPFS and failed patients.
A postimplant 5-mm, three-dimensional periprostatic anulus provides substantial information regarding dosimetric coverage. However, with a median follow-up of 4.2 years, such volumetric and geographic parameters have not proven useful in predicting biochemical outcome in low-risk patients.
Full-text · Article · Jun 2007 · American journal of clinical oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose: Recent studies have suggested that extracapsular permanent prostate brachytherapy treatment margins correlate with biochemical control. It is likely that volumetric dosimetric parameters will be more robust than selected radial measurements. We evaluated the impact of extracapsular volumetric dosimetric parameters on biochemical control in low‐risk patients. Materials and Methods: 263 consecutive low‐risk prostate cancer patients randomized to Pd‐103 versus I‐125 were implanted with a brachytherapy target volume consisting of the prostate with a 5 mm periprostatic margin. The median follow‐up was 4.2 years. All patients were implanted at least 3 years prior to analysis. Within 2 hours of implantation, an axial CT was obtained for post‐implant dosimetry. A 5 mm 3‐dimensional periprostatic annulus was constructed around the prostate gland and evaluated in its entirety and in 90° segments. Dosimetric parameters for the prostate gland and the annulus consisted of V100/150/200 and D90. Biochemical progression‐free survival was defined by a PSA ⩽ 0.5 ng/mL. Results: Mean postoperative dosimetry was significantly different (p < 0.001) between I‐125 versus Pd‐103, respectively, for V100 of 97% versus 93% and D90 of 122% versus 112%. Annulus dosimetry was significant (p < 0.001) for a V100 of 80% versus 70% and a D90 of 91% versus 85% for I‐125 versus Pd‐103, respectively. Six‐year biochemical progression‐free survival was 99.6% versus 99.2% for I‐125 versus Pd‐103 (p = 0.125). The most recent median post‐treatment PSA was 0.1 ng/mL and < 0.04 ng/mL for I‐125 and Pd‐103. Biochemically disease‐free patients had statistically higher prostate and annular dosimetric values. In Cox regression analysis, variants of annulus dosimetry were the best predictors for biochemical control in the I‐125, Pd‐103, and overall cohorts. Conclusions: A postimplant 5 mm 3‐dimensional periprostatic annulus provides substantial information regarding dosimetric coverage and appears to be an important predictor for biochemical outcome in low‐risk patients.
[Show abstract][Hide abstract] ABSTRACT: We identified clinical, treatment and dosimetric parameters associated with the development of urethral strictures following permanent prostate brachytherapy.
From April 1995 through April 2003, 1,186 consecutive patients underwent prostate brachytherapy for clinical stage T1b-T3a NxM0 (2002 American Joint Committee on Cancer) prostate cancer. The treatment plan included supplemental XRT in 625 patients (52.7%) and androgen deprivation therapy in 465 (39.2%). Median followup was 4.3 years. Multiple clinical, treatment and dosimetric parameters were evaluated in univariate and multivariate analyses to identify independent predictors for urethral stricture disease.
A total of 29 patients had brachytherapy related urethral strictures. All strictures involved the BM urethra with a 9-year actuarial risk of 3.6% and a median time to development of 2.4 years. The mean radiation dose to the BM urethra was significantly greater in patients with vs without stricture (p = 0.002). On multivariate analysis the BM urethral dose and supplemental XRT predicted urethral stricture. All except 3 patients were successfully treated with urethral dilation or internal optical urethrotomy.
Brachytherapy related urethral stricture disease correlates highly with the radiation dose to the BM urethra. Careful attention to brachytherapy preplanning and intraoperative execution along with the judicious use of supplemental XRT is essential to minimize the incidence of stricture disease.
Full-text · Article · May 2006 · The Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: Following definitive local treatment for early-stage prostate cancer, preservation of erectile function has been assumed to be most likely following brachytherapy. However, recent studies have demonstrated that brachytherapy-related erectile dysfunction (ED) is more common than initially reported. The exacerbation of brachytherapy-related ED is closely related to several clinical, treatment, and dosimetric parameters including pre-implant erectile function and radiation dose to the proximal penis. The majority of patients with brachytherapy-induced ED respond favorably to oral erectogenic agents.
Full-text · Article · Sep 2005 · Urologic nursing: official journal of the American Urological Association Allied
[Show abstract][Hide abstract] ABSTRACT: To evaluate erectile function after permanent prostate brachytherapy using a validated patient-administered questionnaire and to determine the effect of multiple clinical, treatment, and dosimetric parameters on penile erectile function.
A total of 226 patients with preimplant erectile function determined by the International Index of Erectile Function (IIEF) questionnaire underwent permanent prostate brachytherapy in two prospective randomized trials between February 2001 and January 2003 for clinical Stage T1c-T2c (2002 American Joint Committee on Cancer) prostate cancer. Of the 226 patients, 132 were potent before treatment and, of those, 128 (97%) completed and returned the IIEF questionnaire after brachytherapy. The median follow-up was 29.1 months. Potency was defined as an IIEF score of > or =13. The clinical, treatment, and dosimetric parameters evaluated included patient age; preimplant IIEF score; clinical T stage; pretreatment prostate-specific antigen level; Gleason score; elapsed time after implantation; preimplant nocturnal erections; body mass index; presence of hypertension or diabetes mellitus; tobacco consumption; the volume of the prostate gland receiving 100%, 150%, and 200% of the prescribed dose (V(100/150/200)); the dose delivered to 90% of the prostate gland (D(90)); androgen deprivation therapy; supplemental external beam radiotherapy (EBRT); isotope; prostate volume; planning volume; and radiation dose to the proximal penis.
The 3-year actuarial rate of potency preservation was 50.5%. For patients who maintained adequate posttreatment erectile function, the preimplant IIEF score was 29, and in patients with brachytherapy-related ED, the preimplant IIEF score was 25. The median time to the onset of ED was 5.4 months. After brachytherapy, the median IIEF score was 20 in potent patients and 3 in impotent patients. On univariate analysis, the preimplant IIEF score, patient age, presence of nocturnal erections, and dose to the proximal penis predicted for postimplant erectile function. However, in multivariate analysis, only the preimplant IIEF score and the D(50) to the proximal crura were statistically significant predictors of brachytherapy-related erectile function.
Using a patient-administered validated quality-of-life instrument, brachytherapy-induced ED occurred in 50% of patients at 3 years. On multivariate analysis, preimplant erectile function and the D(50) to the proximal crura were the best predictors of brachytherapy-related erectile function. Because the proximal penis is the most significant treatment-related predictor of brachytherapy-related ED, techniques to minimize the radiation dose to the proximal penis may result in improved rates of potency preservation.
Full-text · Article · Jul 2005 · International Journal of Radiation OncologyBiologyPhysics
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · Jul 2005 · International Journal of Radiation OncologyBiologyPhysics
[Show abstract][Hide abstract] ABSTRACT: Recent studies have implicated the proximal penis as a potential site-specific structure for radiation-related erectile dysfunction (ED). In this study, we evaluated by means of a validated patient-administered questionnaire whether radiation doses to the bulb of the penis and/or the proximal corporeal bodies were predictive for the development of brachytherapy-induced ED.
Thirty patients who underwent permanent prostate brachytherapy between April 1995 and October 1999 and developed brachytherapy-induced ED were paired with 30 similar men who maintained potency after implantation. None of the 60 patients received supplemental external beam radiation therapy, either before or after implantation. Potency was assessed by patient self-administration of the specific erectile questions of the International Index of Erectile Function. The questionnaire consisted of 5 questions with a maximum score of 25. Postimplant potency was defined as an International Index of Erectile Function score > or =11. Mean and median follow-up was 48.3 +/- 14.4 months and 48.0 months, respectively (range: 26.6-79.3 months). The bulb of the penis and the proximal crura were outlined at 0.5-cm intervals on the Day 0 postimplant CT scan. The radiation dose distribution to the bulb of the penis and adjacent crura was defined in terms of the minimum dose delivered to 25%, 50%, 70%, 75%, 90%, and 95% of the bulb (D(25), D(50), D(70), D(75), D(90), and D(95)).
The radiation dose delivered to the bulb of the penis and the proximal crura in men with brachytherapy-induced ED was statistically greater for all evaluated dosimetric parameters (D(25), D(50), D(70), D(75), D(90), and D(95)). Stepwise linear regression analysis indicated that penile bulb dose parameter D(50), the postimplant prostate CT volume, and patient age at implant were predictive of postimplant ED, whereas the crura dose D(25) approached statistical significance. Seventy-five percent of the impotent men had a bulb D(25) >60% of prescribed minimum peripheral dose (mPD), whereas 80% of potent men had a bulb D(25) < or =60% mPD. Using the D(50) bulb parameter, 70% of ED men had a dose >40% mPD, whereas 90% of potent men had a dose < or =40% mPD. Similar cut points for D(25) and D(50) crura doses were 40% and 28% mPD. The crura D(25) cut point was exceeded by 50% of the ED patients and only 7% of the potent patients.
This is the first study to evaluate potency preservation and radiation doses to the proximal penis by means of a validated patient-administered quality-of-life instrument. Our data confirm prior reports that radiation doses to the proximal penis are predictive of brachytherapy-induced ED. In a stepwise linear regression analysis, the strongest predictors of potency preservation were bulb D(50), postimplant prostate CT volume, and patient age. With Day 0 dosimetric evaluation, the penile bulb D(50) and D(25) should be maintained below 40% and 60% mPD, respectively, whereas the crura D(50) and D(25) should be maintained below 40% and 28% mPD, respectively, to maximize posttreatment potency.
Full-text · Article · Dec 2002 · International Journal of Radiation OncologyBiologyPhysics
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether any clinical, treatment, or dosimetric parameters correlated with the development of a prostate-specific antigen (PSA) spike after permanent prostate brachytherapy.
The evaluated population consisted of 218 hormone-naive patients free of biochemical or clinical failure who underwent permanent prostate brachytherapy with or without supplemental external beam radiotherapy for clinical Stage T1b-T3a adenocarcinoma of the prostate gland (1997 AJCC) between August 1995 and November 1999. No patient underwent pre- or postimplant hormonal manipulation, pretreatment seminal vesicle biopsy, or pathologic lymph node staging. In addition, none of the 218 patients possessed equivocal biochemical results (one or two consecutive PSA rises or a declining PSA >1.0 ng/mL). The median patient follow-up was 46.2 months. A PSA spike was defined as a rise of >or=0.2 ng/mL, followed by a durable decline. The clinical parameters evaluated included patient age, clinical T stage, Gleason score, pretreatment PSA level, prostate volume, brachytherapy planning volume, and patient follow-up in months. The evaluated treatment parameters included isotope and use of supplemental external beam radiotherapy. The dosimetric parameters evaluated included the minimal dose received by 90% of the prostate gland (D(90)), the percentage of the prostate volume receiving 100% (V(100)), 150%, and 200% (V(200)) of the prescribed minimal peripheral dose, and the mean, median, maximal, and minimal urethral doses. Biochemical disease-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition with the additional constraint that the most recent PSA level was <or=1.0 ng/mL.
Fifty-two patients (23.9%) developed a PSA spike at a mean and median of 19.5 +/- 9.4 months and 16.3 months (range 6.5-59.9), respectively. The median serum PSA before the PSA spike was 0.50 ng/mL, and the median PSA at the time of the spike was 0.90 ng/mL (range 0.3-3.0). On average, patients experiencing a PSA spike were 3.4 years younger (63.9 vs. 67.3 years, p = 0.002) than patients not experiencing a spike and were more likely to have been implanted with 125I than with 103Pd (32.7% vs. 16.7%, p = 0.006). In addition, the mean first postimplant PSA level was significantly higher in the spike than in the nonspike patients (1.2 vs. 0.7 ng/mL, p <0.001). By 66 months, the mean and median serum PSA levels for the spike and nonspike patients were all <or=0.1 ng/mL. Stratified into three nadir PSA groups, patients with a nadir PSA <or=0.2 ng/mL were significantly less likely to develop a PSA spike than those patients with a PSA nadir >0.2 to <or=0.5 ng/mL or >0.5 to 1.0 ng/mL (20%, 50%, and 80%, respectively, p <0.001). In Cox multivariate regression analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. A postimplant dosimetric threshold of either <115% of the minimal peripheral dose for D(90) or <55% of the prostate volume for V(150) was strongly predictive of a spike. When the variables only determinable after the occurrence of the PSA spike were included in the multivariate analysis, V(150), preimplant PSA level, and nadir PSA were the significant predictors.
Of the patients, 23.9% developed a PSA spike with a median time to development of 16.3 months and a median prespike and median postspike PSA of 0.50 ng/mL and 0.90 ng/mL, respectively. In multivariate analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. At approximately 66 months after implantation, the PSA curves converged for spike and nonspike patients, with a median PSA level <0.1 ng/mL.
Full-text · Article · Nov 2002 · International Journal of Radiation OncologyBiologyPhysics
[Show abstract][Hide abstract] ABSTRACT: To determine the influence of obesity on the development of urinary, bowel, and sexual dysfunction after brachytherapy by means of patient-administered questionnaires. The effect of obesity on dosimetric quality and biochemical outcome was also evaluated.
Thirty-two patients with grade II and III obesity underwent brachytherapy from June 1997 through April 2001. Grade II and III obesity was defined as a body mass index of 35.0 to 39.9 and 40.0 kg/m2 or greater, respectively. Serial International Prostate Symptom Score (IPSS) evaluations were obtained at predetermined intervals. Bowel and sexual function were assessed by a rectal function assessment score (R-FAS) and the specific erectile questions of the International Index of Erectile Function (IIEF). The median follow-up was 26.4 months. An alpha-blocker was initiated before implantation and continued at least until the IPSS normalized. Catheter dependency, alpha-blocker dependency, and the incidence of urethral strictures were also evaluated. The efficacy of sildenafil in brachytherapy-induced erectile dysfunction was also evaluated. Dosimetric parameters evaluated included the percentage of the prostate receiving 100%, 150%, and 200% of the prescribed dose (V100, V150, and V200), the minimal dose received by 90% of the prostate (D90), urethral doses, and rectal doses. Biochemical outcome was determined by the ASTRO consensus conference definition.
Of the 32 patients, 31 (97%) had the urinary catheter permanently removed on day 0, and no patient required a urinary catheter for longer than 1 day. One patient developed a urethral stricture. No patient required a transurethral resection or developed urinary incontinence. On average, the IPSS peaked 2 weeks after implantation and returned to baseline at a median of 8 weeks (mean 16). The post-treatment R-FAS was 3.6. No patient developed a rectal ulcer or fistula. Of the 22 patients who were potent before implantation, 7 (31.8%) maintained potency. With pharmacologic support, 59.1% maintained erections sufficient for vaginal penetration. Day 0 dosimetry demonstrated a median V100 and D90 of 96.5% and 113.5%. At last follow-up, all patients remained free of biochemical failure, with a median prostate-specific antigen level of 0.1 ng/mL.
No difference in quality-of-life parameters was discerned in patients with grade II and III obesity. In addition, the dosimetric quality of the implants was outstanding, and the short-term biochemical outcome was encouraging.