Combination therapy improves prostate cancer survival for patients with potentially lethal prostate cancer: The impact of Gleason pattern 5.

PURPOSE: To investigate the impact of Gleason pattern 5 (GP5) prostate cancer after either external beam radiotherapy (EBRT) or the combination of EBRT with low-dose rate brachytherapy boost (combo). METHODS AND MATERIALS: Between 1998 and 2008, 467 patients with National Comprehensive Cancer Network high-risk prostate cancer were treated with EBRT (n = 326) or combo (low-dose rate to 90-108 Gy using I-125 followed by EBRT) (n = 141). Freedom from biochemical failure, freedom from metastasis (FFM), cancer-specific survival (CSS), and overall survival were evaluated. RESULTS: Combo patients were younger (66 vs. 72 years, p < 0.001) and had fewer comorbidities (Charlson comorbidity index 3.7 vs. 4.4, p < 0.001). EBRT patients had higher tumor stages (T3-4: 30% vs. 21%, p = 0.03) and lower Gleason scores (8-10: 61% vs. 75%, p = 0.01). Androgen deprivation therapy use was similar between cohorts (85% vs. 87%, p = 0.5), but EBRT patients had longer androgen deprivation therapy use (median 14 vs. 12 months, p = 0.05). GP5 predicted worse FFM (p < 0.001, hazard ratio [HR] 3.3, 95% confidence interval [CI]1.8-6.2]) and CSS (p < 0.001, HR 5.9, 95% CI 2.7-12.9) for the EBRT group, but not for the combo group (p = 0.86, HR 0.48, 95% CI 0.1-2.4 for metastasis and p = 0.5, HR 1.6, 95% CI 0.33-8.0 for CSS). In those with GP5 (n = 143), combo was associated with improved outcomes in all endpoints. On univariate analysis, 5-year outcomes for combo vs. EBRT were as follows: freedom from biochemical failure 89% vs. 65%, FFM 89% vs. 67%, CSS 93% vs. 78%, and overall survival 88% vs. 67% (p < 0.05 for all). CONCLUSION: Combo was associated with improved outcomes for men with GP5 prostate cancer. This highlights the importance of local therapy, especially in patients with the highest pathologic grade disease.

Interval to biochemical failure predicts clinical outcomes in patients with high-risk prostate cancer treated by combined-modality radiation therapy.

PURPOSE: To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS: We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). RESULTS: Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, P<.01, 95% confidence interval [CI] 1.4-10.3 for GS 9-10; HR 3.9, P<.0001, 95% CI 2.4-6.5 for IBF ≤18 months) and PCSM (HR 14.8, P<.009, 95% CI 2.0-110 for GS 9-10; HR 4.4, P<.0001, 95% CI 2.4-8.1 for IBF ≤18 months). CONCLUSIONS: Short IBF was highly prognostic for higher DM and PCSM in patients with HiRPCa. The prognostic value of IBF for DM and PCSM was not affected by the radiation therapy regimen or ADT use.

The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.

BACKGROUND: The objective of this study was to determine whether the addition of low-dose-rate brachytherapy or androgen-deprivation therapy (ADT) improves clinical outcome in patients with high-risk prostate cancer (HiRPCa) who received dose-escalated radiotherapy (RT). METHODS: Between 1995 and 2010, 958 patients with HiRPCa were treated at Schiffler Cancer Center (n = 484) or at the University of Michigan (n = 474) by receiving either dose-escalated external-beam RT (EBRT) (n = 510; minimum prescription dose, 75 grays [Gy]; median dose, 78 Gy) or combined-modality RT (CMRT) consisting of (103) Pd implants (n = 369) or (125) I implants (n = 79) both with pelvic irradiation (median prescription dose, 45 Gy). The cumulative incidences of biochemical failure (BF) and prostate cancer-specific mortality (PCSM) were estimated by using the Kaplan-Meier method and Fine and Gray regression analysis. RESULTS: The median follow-up was 63.2 months (interquartile range, 35.4-99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate-specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8-year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%-44%) and 13% (standard error, 11%-15%) compared with 14% (standard error, 12%-16%; P < .0001) and 7% (standard error 6%-9%; P = .003) among patients who received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23-0.52; P < .0001) and 0.41 (95% CI, 0.23-0.75; P < .003), favoring CMRT. Increasing duration of ADT predicted decreased BF (P = .04) and PCSM (P = .001), which was greatest with long-term ADT (BF: HR, 0.33; P < .0001; 95% CI, 0.21-0.52; PCSM: HR, 0.30; P = .001; 95% CI, 0.15-0.6) even in the subgroup that received CMRT. CONCLUSIONS: In this retrospective comparison, both low-dose-rate brachytherapy boost and ADT were associated with decreased risks of BF and PCSM compared with EBRT.

Use of medications or devices for erectile dysfunction among long-term prostate cancer treatment survivors: potential influence of sexual motivation and/or indifference.

OBJECTIVES: To evaluate the potential association between sexual motivation and patterns of erectile dysfunction (ED) therapy among a large cohort of localized prostate cancer treatment survivors. METHODS: The use of medications and devices to improve erections and sexual health-related quality of life (HRQOL) were evaluated using a mailed Expanded Prostate Cancer Index Composite survey administered to 896 men 4 to 8 years after brachytherapy, three-dimensional conformal external beam radiotherapy (3D-CRT), or radical prostatectomy and 112 control men. The responding participants (73% of those surveyed) were classified by prostate cancer treatment, sexual motivation, and ED therapy use. Bivariate and multivariate analyses were used to identify the factors associated with ED therapy use and sexual HRQOL outcome. RESULTS: The quality of erections unassisted by medications or devices was not different among the treatment groups. Prostate cancer survivors used medications or devices for ED more commonly than did the control men (30% versus 13%; P <0.01). One half of the prostate cancer survivors with ED reported indifference regarding their ED (small to no sexual bother despite absent or poor unassisted erections). Conversely, among men who were bothered by poor erections, 48% of the brachytherapy, 61% of the 3D-CRT, and 23% of radical prostatectomy subjects had never tried commonly available medications or devices to improve their erections (P <0.01). The current use of at least one erection aid was an independent determinant of more favorable sexual HRQOL (P <0.01). CONCLUSIONS: Many men who are bothered by posttreatment ED reported never having tried medications or devices to improve their erections. The lack of ED therapy was more prevalent among patients with erectile concerns after brachytherapy or 3D-CRT than after radical prostatectomy, suggesting possible opportunities for improving sexual HRQOL among long-term survivors.

Use and uncertainties of mutual information for computed tomography/ magnetic resonance (CT/MR) registration post permanent implant of the prostate.

Post-implant dosimetric analysis for permanent implant of the prostate benefits from the use of a computed tomography (CT) dataset for optimal identification of the radioactive source (seed) positions and a magnetic resonance (MR) dataset for optimal description of the target and normal tissue volumes. The CT/MR registration process should be fast and sufficiently accurate to yield a reliable dosimetric analysis. Since critical normal tissues typically reside in dose gradient regions, small shifts in the dose distribution could impact the prediction of complication or complication severity. Standard procedures include the use of the seed distribution as fiducial markers (seed match), a time consuming process that relies on the proper identification of signals due to the same seed on both datasets. Mutual information (MI) is more efficient because it uses image data requiring minimal preparation effort. A comparison of MI registration and seed-match registration was performed for twelve patients. MI was applied to a volume limited to the prostate and surrounding structures, excluding most of the pelvic bone structures (margins around the prostate gland were approximately 2 cm right-left, approximately 1 cm anterior-posterior, and approximately 2 cm superior-inferior). Seeds were identified on a 2 mm slice CT dataset using an automatic seed identification procedure on reconstructed three-dimensional data. Seed positions on the 3 mm slice thickness T2 MR data set were identified using a point-and-click method on each image. Seed images were identified on more than one MR slice, and the results used to determine average seed coordinates for MR images and matched seed pairs between CT and MR images. On average, 42% (19%-64%) of the seeds (19-54 seeds) were identified and matched to their CT counterparts. A least-squares method applied to the CT and MR seed coordinates was used to produce the optimum seed-match registration. MI registration and seed match registration angle differences averaged 0.5 degrees, which was not significantly different from zero. Translation differences averaged 0.6 (1.2 standard deviation) mm right-left, -0.5(1.5) mm posterior-anterior, and -1.2(2.0) mm inferior-superior. Registration error estimates were approximately 2 mm for both the MI and seed-match methods. The observed standard deviations in the offset values were consistent with propagation of error. Registration methods as applied here using mutual information and seed matching are consistent, except for a small systematic difference in the inferior-superior axis for a minority of cases (approximately 15%). Cases registered with mutual information and with bony anatomy misregistration of greater than approximately 5 mm should be evaluated for rescan or seed-match registration. The improvement in efficiency of use for the MI registration method is substantial, approximately 30 min compared to several hours using seed match registration.

Dose escalation for localized prostate cancer: substantial benefit observed with 3D conformal therapy.

PURPOSE: To determine the effect of radiation dose escalation on biochemical and/or disease failure in patients with localized prostate cancer treated with three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Between May 1987 and December 2000, 1473 patients were assessed after treatment with 3D-CRT. The mean patient age was 70.4 +/- 6.8 years, 1316 patients had T1-T2 disease, and 1150 had Gleason score 20 ng/mL or Gleason score >or=8) compared with 448 low-risk patients (stage T1-T2 and Gleason score

Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer.

PURPOSE: Health-related quality-of-life (HRQOL) concerns are pivotal in choosing prostate cancer therapy. However, concurrent HRQOL comparison between brachytherapy, external radiation, radical prostatectomy, and controls is hitherto lacking. HRQOL effects of hormonal adjuvants and of cancer control after therapy also lack prior characterization. PATIENTS AND METHODS: A cross-sectional survey was administered to patients who underwent brachytherapy, external-beam radiation, or radical prostatectomy during 4 years at an academic medical center and to age-matched controls. HRQOL among controls was compared with therapy groups. Comparison between therapy groups was performed using regression models to control covariates. HRQOL effects of cancer progression were evaluated. RESULTS: One thousand fourteen subjects participated. Compared with controls, each therapy group reported bothersome sexual dysfunction; radical prostatectomy was associated with adverse urinary HRQOL; external-beam radiation was associated with adverse bowel HRQOL; and brachytherapy was associated with adverse urinary, bowel, and sexual HRQOL (P < or =.0002 for each). Hormonal adjuvant symptoms were associated with significant impairment (P <.002). More than 1 year after therapy, several HRQOL outcomes were less favorable among subjects after brachytherapy than after external radiation or radical prostatectomy. Progression-free subjects reported better sexual and hormonal HRQOL than subjects with increasing prostate-specific antigen (P <.0001). CONCLUSION: Long-term HRQOL after prostate brachytherapy showed no benefit relative to radical prostatectomy or external-beam radiation and may be less favorable in some domains. Hormonal adjuvants can be associated with significant impairment. Progression-free survival is associated with HRQOL benefits. These findings facilitate patient counseling regarding HRQOL expectations and highlight the need for prospective studies sensitive to urinary irritative and hormonal concerns in addition to incontinence, sexual, and bowel HRQOL domains.