Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy.

OBJECTIVE: To evaluate the relationship between pre-treatment erectile function and all-cause mortality in patients with prostate cancer treated with brachytherapy. PATIENTS AND METHODS: In all, 1279 consecutive patients with clinically localized prostate cancer and pre-implant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) underwent brachytherapy. Potency was defined as an IIEF-6 score of ≥13 without pharmacological or mechanical support. Patients were stratified into IIEF-6-score cohorts (≤12, 13-23 and 24-30). The median follow-up was 5.0 years. RESULTS: The 8-year overall survival (OS) of the study population was 85.1%. The 8-year OS for IIEF-6scores ≤12, 13-23 and 24-30 were 78.0%, 92.8% and 91.4%, respectively (P < 0.001). Cardiovascular events accounted for a significant portion of deaths in each IIEF-6 group. When combined with other risk factors for cardiovascular disease, an IIEF-6 score of ≤12 had an additive effect on all-cause mortality (IIEF-6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%). CONCLUSIONS: A pre-implant IIEF-6score of ≤12 was associated with a higher incidence of all-cause mortality. Pre-treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients. Aggressive treatment of medical co-morbidity is warranted to impactOS.

Prostate cancer death is unlikely in high-risk patients following quality permanent interstitial brachytherapy.

OBJECTIVE: To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in high-risk prostate cancer brachytherapy patients. PATIENTS AND METHODS: From April 1995 to June 2005, 284 patients with high-risk prostate cancer (Gleason score ≥ 8 or prostate-specific antigen > 20 ng/mL or clinical stage ≥ T2 c) underwent brachytherapy. Supplemental external beam radiation therapy was given to 257 (90.5%) patients and 179 (63.0%) received androgen deprivation therapy (ADT). Median follow up was 7.8 years. The median post-implant day 0 D90 was 118.9% of prescription dose. Patients with metastatic prostate cancer or castrate-resistant disease without obvious metastases who died of any cause were classified as dead from prostate cancer. Multiple parameters were evaluated for impact on survival. RESULTS: Twelve-year CSS, bPFS and OS were 94.2%, 89.0% and 69.7%. On multivariate analysis, bPFS was best predicted by percent positive biopsies and ADT. The analysis failed to identify any predictors for CSS, while OS was highly correlated with patient age, percent positive biopsies and diabetes. Fourteen percent of patients died from diseases of the heart, while 8%, 8% and 6% of patients died from non-prostate cancer, other causes and prostate cancer, respectively. When OS was stratified by patients with 0-3 vs ≥ 4 comorbidities, the 12-year OS was 73.0% and 52.7% (P = 0.036). CONCLUSIONS: High-quality brachytherapy results in favourable bPFS and CSS for high-risk patients. Death from diseases of the heart is more than twice as likely as death from prostate cancer. Strategies to improve cardiovascular health may positively impact OS.

Relationship between prostate cancer mortality and number of unfavourable risk factors in men treated with definitive brachytherapy.

OBJECTIVE: To explore whether the number of unfavourable pretreatment risk factors predicts cause-specific mortality in men treated with prostate brachytherapy. PATIENTS AND METHODS: Between April 1995 and March 2006, 739 patients were treated who had at least one of the following adverse risk factors: pretreatment prostate-specific antigen (PSA) level of >10 ng/mL, a Gleason score of > or =7, clinical stage > or =T2b, or a PSA velocity (PSAV) of >2 ng/mL/year. Supplemental external beam radiotherapy (EBRT) was delivered to 464 (62.8%) men and 301 (40.7%) received androgen deprivation therapy (ADT). Of men with more than two risk factors, 87% received EBRT and 62% received ADT. RESULTS: The biochemical progression-free survival (bPFS), cause-specific survival (CSS) and overall survival for all patients were 95.0%, 97.9% and 70.0% at 12 years. Men with three or four risk factors had a prostate cancer-specific mortality (PCSM) at 12 years of 5.3%, vs 1.7% for men with one or two risk factors (P= 0.006). When 'percentage of positive biopsy cores >50%' replaced PSAV as a risk factor, men with two or more risk factors had a PCSM of 8.9%, vs 1.0% for men with one or two risk factors (P= 0.001). There was no difference in all-cause mortality between the groups in either analysis. CONCLUSION: Multimodal brachytherapy results in high rates of bPFS and CSS, even for men with several unfavourable risk factors. Men with two or more unfavourable risk factors had a slightly greater risk of PCSM and no difference in all-cause mortality. The presence of three or four unfavourable intermediate-risk factors does not appear to clearly identify a group that requires further treatment intensification, although the percentage of positive cores might be more predictive than PSAV.

Androgen deprivation therapy: a survival benefit or detriment in men with high-risk prostate cancer?

Androgen deprivation therapy (ADT) has been used in the management of prostate cancer for more than four decades. Initially, hormone therapy was given largely for palliation of symptomatic metastases. Following several randomized trials of patients with intermediate- to high-risk prostate cancer that demonstrated improvements in biochemical control and survival with the addition of ADT to external beam radiotherapy, there was a dramatic increase in the use of hormone therapy in the definitive setting. More recently, the safety of ADT has been questioned, as some studies have suggested an association of hormone therapy with increased cardiovascular morbidity and mortality. This is particularly worrisome in light of practice patterns that show ADT use extrapolated to situations for which there has been no proven benefit. In the setting of dose escalation with modern radiotherapy, in conjunction with the latest concerns about cardiovascular morbidity with ADT, the magnitude of expected benefit along with potential risks of ADT use must be carefully considered for each patient.

Prostate brachytherapy in men > or =75 years of age.

PURPOSE: To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in prostate cancer patients aged > or =75 years undergoing brachytherapy with or without supplemental therapies. METHODS AND MATERIALS: Between April 1995 and August 2004, 145 consecutive patients aged > or =75 years underwent permanent prostate brachytherapy. Median follow-up was 5.8 years. Biochemical progression-free survival was defined by a prostate-specific antigen level < or =0.40 ng/mL after nadir. Patients with metastatic prostate cancer or hormone-refractory disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on survival. RESULTS: Nine-year CSS, bPFS, and OS rates for the entire cohort were 99.3%, 97.1%, and 64.5%, respectively. None of the evaluated parameters predicted for CSS, whereas bPFS was most closely predicted by percentage positive biopsies. Overall survival and non-cancer deaths were best predicted by tobacco status. Thirty-seven patients have died, with 83.8% of the deaths due to cardiovascular disease (22 patients) or second malignancies (9 patients). To date, only 1 patient (0.7%) has died of metastatic prostate cancer. CONCLUSIONS: After brachytherapy, high rates of CSS and bPFS are noted in elderly prostate cancer patients. Overall, approximately 65% of patients are alive at 9 years, with survival most closely related to tobacco status. We believe our results support an aggressive locoregional approach in appropriately selected elderly patients.

Primary causes of death after permanent prostate brachytherapy.

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

The morbidity of transperineal template-guided prostate mapping biopsy.

OBJECTIVE: To evaluate the effect of transperineal template-guided prostate mapping biopsy (TTMB) on urinary, bowel and erectile function. PATIENTS AND METHODS: In all, 129 men had TTMB; a median of 56 biopsy cores were obtained per patient. Tamsulosin (0.8 mg daily) was initiated 2 days before TTMB and continued for 2 weeks. The International Prostate Symptom Score (IPSS), Rectal Function Assessment Score (R-FAS), International Index of Erectile Function (IIEF)-6 and the postvoid residual volume (PVR) were assessed at baseline and after 30 days, except for the IPSS, which was also assessed at 7 days. Several variables were evaluated as predictors of TTMB-induced morbidity. RESULTS: The mean patient age was 64.7 years with a mean prostate volume of 74.3 mL; 60 men (46.5%) were diagnosed with prostate cancer. After TTMB, 39.4%, 7.1% and 1.6% of patients remained catheter-dependent at 0, 3 and 6 days. The median catheter-dependency was 0, 1, 2 and 3 days for prostate volumes of <60, 60-90, 90-120 and >120 mL, respectively. No patient remained catheter- dependent for >12 days or required a transurethral resection secondary to TTMB. The mean IPSS before TTMB was 10.4, and was 4.6 and 3.8 at 7 and 30 days. At baseline and 30 days the mean PVR was 35 and 40 mL, and the median R-FAS and IIEF scores for patients potent before TTMB were 2.0 and 2.2, and 27.0 and 26.0, respectively. CONCLUSIONS: TTMB is a promising procedure for diagnosing prostate cancer. TTMB-related morbidity differs from that of standard TRUS biopsy primarily in the incidence of temporary urinary retention, and is comparable in terms of urinary, bowel and erectile function.

Interstitial brachytherapy should be standard of care for treatment of high-risk prostate cancer.

High-risk prostate cancer represents a therapeutic challenge for both the urologist and radiation oncologist. Biochemical outcomes with radical prostatectomy and external-beam radiation therapy are poor in this subset of patients. These unfavorable results have led some to believe that high-risk prostate cancer is not curable with conventional treatment approaches, which has been an impetus for many of the current trials using neoadjuvant chemotherapy and prostatectomy. With the established efficacy of interstitial brachytherapy, these efforts are likely excessive. Most modern trials indicate excellent biochemical control rates among high-risk patients treated with an aggressive locoregional approach that includes brachytherapy. A thoughtful review of the literature would suggest that interstitial brachytherapy offers a therapeutic advantage over other local treatment modalities and should be considered standard treatment for aggressive organ-confined prostate cancer.

Isotope and patient age predict for PSA spikes after permanent prostate brachytherapy.

PURPOSE: To evaluate prostate-specific antigen (PSA) spikes after permanent prostate brachytherapy in low-risk patients. METHODS AND MATERIALS: The study population consisted of 164 prostate cancer patients who were part of a prospective randomized trial comparing (103)Pd and (125)I for low-risk disease. Of the 164 patients, 61 (37.2%) received short-course androgen deprivation therapy. The median follow-up was 5.4 years. On average, 11.1 post-treatment PSA measurements were obtained per patient. Biochemical disease-free survival was defined as a PSA level of < or =0.40 ng/mL after nadir. A PSA spike was defined as an increase of > or =0.2 ng/mL, followed by a durable decline to prespike levels. Multiple parameters were evaluated as predictors for a PSA spike. RESULTS: Of the 164 patients, 44 (26.9%) developed a PSA spike. Of the 46 hormone-naive (125)I patients and 57 hormone-naive (103)Pd patients, 21 (45.7%) and 8 (14.0%) developed a PSA spike. In the hormone-naive patients, the mean time between implantation and the spike was 22.6 months and 18.7 months for (125)I and (103)Pd, respectively. In patients receiving neoadjuvant androgen deprivation therapy, the incidence of spikes was comparable between isotopes ((125)I 28.1% and (103)Pd 20.7%). The incidence of spikes was substantially different in patients <65 years vs. > or =65 years old (38.5% vs. 16.3%). On multivariate Cox regression analysis, patient age (p < 0.001) and isotope (p = 0.002) were significant predictors for spike. CONCLUSION: In low-risk prostate cancer, PSA spikes are most common in patients implanted with (125)I and/or <65 years of age. Differences in isotope-related spikes are most pronounced in hormone-naive patients.

Intraoperative ultrasound-fluoroscopy fusion can enhance prostate brachytherapy quality.

PURPOSE: To evaluate a transrectal ultrasound (TRUS)-fluoroscopy fusion-based intraoperative dosimetry system. METHOD AND MATERIALS: Twenty-five patients were treated for prostate cancer with Pd-103 implantation. After the execution of the treatment plan, two sets of TRUS images were collected using the longitudinal and axial transducers of a biplanar probe. Then, three fluoroscopic images were acquired at 0, -15 and +15 degrees . The three-dimensional locations of all implanted seeds were reconstructed from fluoroscopic images. A subset of the implanted seeds was manually identified in TRUS images and used as fiducial markers to perform TRUS-fluoroscopy fusion. To improve the implant quality, additional seeds were placed if adverse isodose patterns were identified during visual inspection. If additional seeds were placed, intraoperative dosimetry was repeated. Day 0 computed tomography-based dosimetry was compared with final intraoperative dosimetry to validate dosimetry achieved in the implant suite. RESULTS: An average of additional 4.0 seeds was implanted in 16 patients after initial intraoperative dose evaluation. Based on TRUS-fluoroscopy fusion-based dosimetry, the V100 improved from 86% to 93% (p = 0.005), whereas D90 increased from 94% to 109% (p = 0.011) with the guided additional seed implantation. No statistical difference was observed in V200 and V300 values. V100 and D90 values were 95 +/- 4% and 120 +/- 24%, respectively, based on the final intraoperative dosimetry evaluation, compared with 95 +/- 4% and 122 +/- 24%, respectively, based on Day 0 computed tomography-based dosimetry. CONCLUSIONS: Implantation of extra seeds based on TRUS-fluoroscopy fusion-based intraoperative dosimetry can improve the final V100 and D90 values with minimal increase in V200 and V300 values.

Androgen deprivation therapy does not impact cause-specific or overall survival in high-risk prostate cancer managed with brachytherapy and supplemental external beam.

PURPOSE: To determine cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in high-risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. METHODS AND MATERIALS: Between April 1995 and July 2002, 204 patients with high-risk prostate cancer (Gleason score > or = 8 or prostate-specific antigen [PSA] >20 ng/mL or clinical stage > or = T2c) underwent brachytherapy. Median follow-up was 7.0 years. The bPFS was defined by a PSA < or = 0.40 ng/mL after nadir. Multiple clinical, treatment, and dosimetric parameters were evaluated for the impact on survival. RESULTS: The 10-year CSS, bPFS, and OS were 88.9%, 86.6%, and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naive, ADT < or = 6 months, and ADT >6 month cohorts (79.7% vs. 95.% vs. 89.9%, p = 0.032). Androgen deprivation therapy (ADT) did not impact CSS or OS. For bPFS patients, the median posttreatment PSA was <0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS, whereas percent positive biopsies and duration of ADT best predicted for bPFS. The OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died, with 26 of the deaths from cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. CONCLUSIONS: The ADT improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact OS.

The impact of acute urinary morbidity on late urinary function after permanent prostate brachytherapy.

PURPOSE: Acute prostate brachytherapy-related morbidity is dominated by urinary symptomatology. In this study, we evaluated the effect of severe early brachytherapy-related urinary morbidity on late urinary function. METHODS AND MATERIALS: From January 1998 to September 2003, 1029 patients were implanted for clinical stage T1b-T3a (2002 American Joint Committee on Cancer [AJCC] criteria) prostate cancer. Five hundred sixteen (50.1%) received supplemental external beam radiation therapy and 440 (42.8%) received androgen deprivation therapy. Severe acute urinary morbidity (SAUM) was defined as a dysuria frequency score of at least 4 (of 5), a dysuria severity score of at least 8 (of 10), an internation prostate symptom score (IPSS) elevated to at least 30 or 15 above preimplant value for 4 weeks, and/or requirement of a urinary catheter for at least 5 days. Dysuria severity and frequency resolution were defined as a return to within one point of baseline. IPSS resolution was defined as a return to within two points of baseline. RESULTS: Of the 1029 patients, 175 met at least one of the criteria for inclusion. Dysuria frequency resolved in 5.0 vs. 1.3 weeks and dysuria severity in 5.7 vs. 1.4 weeks, for patients with and without SAUM. The mean time for IPSS resolution was 13.8 vs. 6.6 weeks, for patients with and without SAUM. The incidence of transurethral resection (2.3% [4/173] vs. 1.5% [13/841]) and bulbomembranous urethral strictures (2.2% [4/175] vs. 1.8% [15/854]) were comparable among patients with and without SAUM. CONCLUSIONS: Patients experiencing brachytherapy-related SAUM have long-term urinary function and complications comparable to patients who did not develop SAUM.

A prospective randomized comparison of stranded vs. loose 125I seeds for prostate brachytherapy.

PURPOSE: To compare seed loss and dosimetric parameters between stranded and loose 125I seeds (LS) for prostate brachytherapy. METHODS AND MATERIALS: Sixty-four patients with 1997 American Joint Commission on Cancer (AJCC) clinical stage T1c or T2a prostate carcinoma were prospectively randomized to brachytherapy (144Gy) with RAPID Strand 125I seeds (RS) vs. LS (Oncura, Plymouth Meeting, PA) The treatment plan for each patient was devised before randomization, and was not modified based on the randomization. Each patient underwent magnetic resonance, computed tomography, and plain film radiographs on the day of the implant (Day 0) and 30 days later (Day 30). RESULTS: Overall, 21 of 62 patients (30%) experienced seed loss. Seed loss occurred in 15 of 32 of LS patients (47%) vs. 6 of 30 RS patients (23%; p=0.053). Mean seed loss was 1.09 in the LS patient vs. 0.43 in RS patients (p=0.062). Eight LS patients (25%) lost multiple seeds, compared to 3 stranded patients (10%). Despite the lesser degree of seed loss in patients who received stranded seeds, they had a paradoxical trend toward lower V100 and D90 values. CONCLUSION: This prospective randomized trial showed a strong trend toward a decrease in postimplant seed loss with stranded seeds. Improved seed retention may be more advantageous in a setting of less generous periprostatic coverage. The lowered risk seed migration seen with stranded seeds would presumably also decrease the likelihood of lung or cardiac seed embolization.

Interstitial implant alone or in combination with external beam radiation therapy for intermediate-risk prostate cancer: a survey of practice patterns in the United States.

PURPOSE: This study is aimed at understanding and defining the current patterns of care with respect to prostate brachytherapy for patients with intermediate-risk localized disease in the combined academic and community setting. METHODS AND MATERIALS: A nomogram-based survey was developed at the Seattle Prostate Institute defining the accepted criteria for intermediate-risk prostate cancer. Patients were defined as having intermediate-risk prostate cancer if they met one of the following criteria: prostate-specific antigen (PSA) >10 ng/dL, Gleason score (GS) > or = 7, or cT2b or cT2c disease. Additional potential predictive factors including perineural invasion (PNI), GS 3+4 vs. 4+3, and high-volume disease were included. RESULTS: In the absence of PNI, all of those surveyed would perform monotherapy for intermediate-risk patients, GS 7 (3+4) or PSA 10-20, with cT1c and <30% cores +. Up to 80% would perform monotherapy for patients with cT1c, GS 7 (4+3), and <30% cores +. Eighty to 90% of physicians would perform an implant alone with cT2a and either a PSA of 10-20 or GS of 7 (3+4) and <30% cores +. Fifty to 60% of those surveyed stated that they would treat a patient with cT2b disease, GS 7 (3+4), or PSA 11-20, with less than two-thirds of the biopsy cores positive in the absence of PNI. CONCLUSIONS: This Patterns of Care (POC) study reveals that certain subsets of intermediate-risk localized prostate cancer patients are considered appropriate candidates for an interstitial implant alone.

PSA spike after brachytherapy For localized prostate cancer.

A common concern for patients who have undergone treatment for prostate cancer and their families is an elevation or spike in the PSA level following definitive treatment. A number of factors can be responsible for this, but often the PSA spike may be benign. An informed health care worker can reasonably assess whether this is the case, and can help to alleviate the fears of the patient and his family.

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

PURPOSE: To 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 METHODS: Patient 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. RESULTS: The 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. CONCLUSIONS: Supplemental 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.

Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy.

PURPOSE: To determine if androgen-deprivation therapy (ADT) has an impact on cause-specific, biochemical progression-free, or overall survival after prostate brachytherapy. METHODS AND MATERIALS: From April 1995 through June 2002, 938 consecutive patients underwent brachytherapy for clinical Stage T1b to T3a (2002 AJCC) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. A total of 382 patients (40.7%) received ADT with a duration of 6 months or less in 277 and more than 6 months in 105. The median follow-up was 5.4 years. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. RESULTS: The 10-year cause-specific, biochemical progression-free, and overall survival rates for the entire cohort were 96.4%, 95.9%, and 78.1%, respectively. Except for biochemical progression-free survival in high-risk patients, ADT did not statistically impact any of the three survival categories. A Cox linear-regression analysis demonstrated that Gleason score was the best predictor of cause-specific survival, whereas percent-positive biopsies, prostate volume, and risk group predicted for biochemical progression-free survival. Patient age and tobacco use were the strongest predictors of overall survival. One hundred two patients have died, with 80 of the deaths a result of cardiovascular disease (54) and second malignancies (26). To date, only 12 patients have died of metastatic prostate cancer. CONCLUSIONS: After brachytherapy, androgen-deprivation therapy did not have an impact on cause-specific or overall survival for any risk group; however, ADT had a beneficial effect on biochemical progression-free survival in high-risk patients. Cardiovascular disease and second malignancies far outweighed prostate cancer as competing causes of death.

The influence of isotope and prostate volume on urinary morbidity after 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 secondary to bladder outlet obstruction after prostate brachytherapy. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Temporal relationship between prostate brachytherapy and the diagnosis of colorectal cancer.

PURPOSE: To identify the location of pretreatment and posttreatment colorectal malignancies and posttreatment colorectal polyps in patients with clinically localized prostate cancer managed with brachytherapy. METHODS AND MATERIALS: From April 1995 through July 2004, 1,351 consecutive patients underwent brachytherapy for clinical stage T1b-T3a (American Joint Committee on Cancer, 2002) prostate cancer. Supplemental external beam radiotherapy (XRT) was administered to 699 patients. The median follow-up was 4.6 years. Operative and pathology reports were reviewed for all patients with pretreatment and posttreatment colorectal cancer and posttreatment colorectal polyps. Multiple parameters were evaluated for the development of colorectal cancer or colorectal polyps. RESULTS: Colorectal cancer was diagnosed in 23 and 25 patients before and after prostate brachytherapy, respectively. No differences were identified in the distribution of colorectal cancers either before or after treatment (3 and 4 rectal cancers in the pre- and postbrachytherapy cohorts). Thirty-five of the 48 colorectal cancers (73%) were diagnosed within 5 years of brachytherapy with a peak incidence 1 year after brachytherapy. One hundred ninety-two colorectal polyps were diagnosed after brachytherapy, 160 (83%) occurred within 4 years of brachytherapy, and only 27 (14%) were located in the rectum. In multivariate Cox regression analysis, prostate D(90) (minimum percentage of the dose covering 90% of the target volume) predicted for posttreatment colorectal cancer. Rectal polyps were most closely related to patient age and percent positive biopsies, whereas sigmoid/colon polyps were best predicted by patient age, planning volume, and supplemental XRT. CONCLUSIONS: Colorectal cancer was diagnosed with equal frequency before and after brachytherapy with comparable geographic distributions. In addition, the vast majority of postbrachytherapy colorectal polyps were located beyond the confines of the rectum.

Treatment of prostate cancer in obese patients.

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States. Obesity is now linked with numerous health conditions, including many oncologic diagnoses. Its association with prostate cancer, the most prevalent cancer in men, has also been investigated, with studies suggesting a direct relationship between increasing obesity and prostate cancer mortality. Outcomes data for specific interventions in obese patients with prostate cancer have only recently begun to emerge. Surgery, while feasible even in the very obese, may result in less than optimal cancer control rates. Brachytherapy data are emerging, and are promising. No outcomes data are available for the use of external-beam radiation in obese patients. Long-term data for external-beam radiation, as well as for surgery and brachytherapy, are required to determine the most appropriate treatment for obese patients with prostate cancer. These data, coupled with a more thorough understanding of the biochemical relationship between obesity and prostate cancer, will be necessary to make optimal management decisions for obese patients with prostate cancer in the future.