RESUMEN
BACKGROUND: Erectile dysfunction remains the most common side effect from radical treatment of localized prostate cancer. We hypothesized that the use of vessel-sparing radiotherapy, analogous to the functional anatomy approach of nerve-sparing radical prostatectomy (RP), would improve erectile function preservation while maintaining tumor control for men with localized prostate cancer. OBJECTIVE: To determine erectile function rates after vessel-sparing radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: Men with localized prostate cancer were enrolled in a phase 2 single-arm trial (NCT02958787) at a single academic center. INTERVENTION: Patients received vessel-sparing radiotherapy utilizing a planning MRI and MRI-angiogram to delineate and avoid the erectile vasculature. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Both physician- and patient-reported inventories were used to capture erectile function at baseline and at 2 and 5 yr after treatment. Validated model-based comparisons were performed to compare vessel-sparing results to nerve-sparing RP and conventional radiotherapy. RESULTS AND LIMITATIONS: From 2001 to 2009, 135 men underwent vessel-sparing radiotherapy. After a planned interim analysis, the trial was stopped after meeting the primary endpoint. The median follow-up was 8.7 yr, with a ≥94% response rate to all inventories at each time point. At 5 yr, 88% of patients were sexually active with or without the use of sexual aids. The 2-yr erectile function rates were significantly improved with vessel-sparing radiotherapy (78%, 95% confidence interval [CI] 71-85%) compared to modeled rates for convention radiotherapy (42%, 95% CI 38-45%; p<0.001) or nerve-sparing prostatectomy (24%, 95% CI 22-27%; p<0.001). At 2 yr after treatment, 87% of baseline-potent men retained erections suitable for intercourse. The 5- and 10-yr rates of biochemical relapse-free survival were 99.3% and 89.9%, and at 5 yr the biochemical failures were limited to the National Comprehensive Cancer Network high-risk group. The single-arm design is a limitation. CONCLUSIONS: Vessel-sparing radiotherapy appears to more effectively preserve erectile function when compared to historical series and model-predicted outcomes following nerve-sparing RP or conventional radiotherapy, with maintenance of tumor control. This approach warrants independent validation. PATIENT SUMMARY: In this interim analysis we looked at using a novel approach to spare critical erectile structures to preserve erectile function after prostate cancer radiotherapy. We found that almost 90% of patients at 5 yr after treatment remained sexually active, significantly higher than previous studies with surgery or radiotherapy.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Impotencia Vasculogénica/prevención & control , Tratamientos Conservadores del Órgano/métodos , Erección Peniana , Neoplasias de la Próstata/radioterapia , Planificación de la Radioterapia Asistida por Computador , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Anciano , Supervivencia sin Enfermedad , Humanos , Impotencia Vasculogénica/etiología , Impotencia Vasculogénica/fisiopatología , Angiografía por Resonancia Magnética , Masculino , Michigan , Persona de Mediana Edad , Tratamientos Conservadores del Órgano/efectos adversos , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Braquiterapia/métodos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Anciano , Antagonistas de Andrógenos/uso terapéutico , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/terapia , Dosificación Radioterapéutica , Tasa de SupervivenciaRESUMEN
PURPOSE: A range of (125)I isotope activities is used in permanent prostate implants. In this study, we compared the implant quality and cost in patients randomized to high-source or low-source strength permanent implants. METHODS AND MATERIALS: Forty patients were randomized to receive high (0.76 microGy/m(2)/h) or low (0.4 microGy/m(2)/h) seed strength implants. The two treatment arms had a comparable mix of primary and boost patients and underwent implantation by the same team. The postimplant dosimetric evaluation was performed using CT (seed position) and T(2)-weighted MRI (prostate) scans registered using mutual information techniques. The implant quality parameters were assessed by dose indexes (ratio of achieved dose to planned dose) to quantify the relative error tolerance. RESULTS: The high-source strength implants had better dose coverage as defined by the dose index; a larger percentage of volume receiving 100% of the prescribed dose as determined by CT (V(100)) (96.3% +/- 3.5% vs. 90.4% +/- 5.3%; p <0.002); lower seed cost (2400 US dollar vs. 3840 US dollar average/case); and took less operating room time on average (67 +/- 16 min vs. 85 +/- 20 min; p <0.004). Finally, the differences in the rectal and urethral doses were not statistically significant between the two treatment arms. CONCLUSION: All 40 patients received an excellent implant as indicated by the CT V(100). Unless long-term toxicity differs, high-source strength seed implants improve the probability of excellent implant quality and decrease the average cost of permanent prostate implants.