Gregg H. Goldin

Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer

CONTEXT There has been rapid adoption of newer radiation treatments such as intensity-modulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies. OBJECTIVE To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment. DESIGN, SETTING, AND PATIENTS Population-based study using Surveillance, Epidemiology, and End Results-Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer. MAIN OUTCOME MEASURES Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy. RESULTS Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score-adjusted analyses (N = 12,976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86-0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65-0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03-1.20). Intensity-modulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73-0.89). In a propensity score-matched comparison between IMRT and proton therapy (n = 1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55-0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy. CONCLUSIONS Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation therapy was associated with less gastrointestinal morbidity and fewer hip fractures but more erectile dysfunction; IMRT compared with proton therapy was associated with less gastrointestinal morbidity.

Comparative effectiveness of intensity-modulated radiotherapy and conventional conformal radiotherapy in the treatment of prostate cancer after radical prostatectomy.

IMPORTANCE Comparative effectiveness research of prostate cancer therapies is needed because of the development and rapid clinical adoption of newer and costlier treatments without proven clinical benefit. Radiotherapy is indicated after prostatectomy in select patients who have adverse pathologic features and in those with recurrent disease. OBJECTIVES To examine the patterns of use of intensity-modulated radiotherapy (IMRT), a newer, more expensive technology that may reduce radiation dose to adjacent organs compared with the older conformal radiotherapy (CRT) in the postprostatectomy setting, and to compare disease control and morbidity outcomes of these treatments. DESIGN AND SETTING Data from the Surveillance, Epidemiology, and End Results-Medicare-linked database were used to identify patients with a diagnosis of prostate cancer who had received radiotherapy within 3 years after prostatectomy. PARTICIPANTS Patients who received IMRT or CRT. MAIN OUTCOMES AND MEASURES The outcomes of 457 IMRT and 557 CRT patients who received radiotherapy between 2002 and 2007 were compared using their claims through 2009. We used propensity score methods to balance baseline characteristics and estimate adjusted incidence rate ratios (RRs) and their 95% CIs for measured outcomes. RESULTS Use of IMRT increased from zero in 2000 to 82.1% in 2009. Men who received IMRT vs CRT showed no significant difference in rates of long-term gastrointestinal morbidity (RR, 0.95; 95% CI, 0.66-1.37), urinary nonincontinent morbidity (0.93; 0.66-1.33), urinary incontinence (0.98; 0.71-1.35), or erectile dysfunction (0.85; 0.61-1.19). There was no significant difference in subsequent treatment for recurrent disease (RR, 1.31; 95% CI, 0.90-1.92). CONCLUSIONS AND RELEVANCE Postprostatectomy IMRT and CRT achieved similar morbidity and cancer control outcomes. The potential clinical benefit of IMRT in this setting is unclear. Given that IMRT is more expensive, its use for postprostatectomy radiotherapy may not be cost-effective compared with CRT, although formal analysis is needed.

Racial Differences in Diffusion of Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

Intensity-modulated radiation therapy (IMRT), an innovative treatment option for prostate cancer, has rapidly diffused over the past decade. To inform our understanding of racial disparities in prostate cancer treatment and outcomes, this study compared diffusion of IMRT in African American (AA) and Caucasian American (CA) prostate cancer patients during the early years of IMRT diffusion using the Surveillance, Epidemiology and End Results (SEER)–Medicare linked database. A retrospective cohort of 947 AA and 10,028 CA patients diagnosed with localized prostate cancer from 2002 through 2006, who were treated with either IMRT or non-IMRT as primary treatment within 1 year of diagnoses was constructed. Logistic regression was used to examine potential differences in diffusion of IMRT in AA and CA patients, while adjusting for socioeconomic and clinical covariates. A significantly smaller proportion of AA compared with CA patients received IMRT for localized prostate cancer (45% vs. 53%, p < .0001). Racial differences were apparent in multivariable analysis though did not achieve statistical significance, as time and factors associated with race (socioeconomic, geographic, and tumor related factors) explained the preponderance of variance in use of IMRT. Further research examining improved access to innovative cancer treatment and technologies is essential to reducing racial disparities in cancer care.

Patient-reported quality of life during definitive and postprostatectomy image-guided radiation therapy for prostate cancer

PURPOSE The importance of patient-reported outcomes is well-recognized. Long-term patient-reported symptoms have been described for individuals who completed radiation therapy (RT) for prostate cancer. However, the trajectory of symptom development during the course of treatment has not been well-described in patients receiving modern, image-guided RT. METHODS AND MATERIALS Quality-of-life data were prospectively collected for 111 prostate cancer patients undergoing RT using the validated Prostate Cancer Symptom Indices, which assessed 5 urinary obstructive/irritative and 6 bowel symptoms. Patients who received definitive RT (N = 73) and postprostatectomy RT (N = 38) were analyzed separately. The frequency and severity of symptoms over multiple time points are reported. RESULTS An increasing number of patients had clinically meaningful urinary and bowel symptoms over the course of RT. A greater proportion of patients undergoing definitive RT reported clinically meaningful urinary symptoms at the end of RT compared with baseline in terms of flow (33% vs 19%) and frequency (39% vs 18%). Individuals receiving postprostatectomy radiation also reported an increase in symptoms including frequency (29% vs 3%) and nocturia (50% vs 21%). Clinically meaningful bowel symptoms were less commonly reported. Patients receiving definitive RT reported an increase in diarrhea (9% vs 4%) and urgency (12% vs 6%) at the completion of RT compared with baseline. Both bowel and urinary symptoms approached their baseline levels by the time of first follow-up after treatment completion. The majority of patients who had clinically meaningful urinary or bowel symptoms during RT did not have them at 2 years or beyond, and development of new symptoms in the long term was uncommon. CONCLUSIONS There is a modest increase in urinary and bowel symptoms over the course of treatment for individuals receiving definitive and postprostatectomy image-guided RT. These data can help inform both providers and patients regarding the trajectory of symptoms and allow for reasonable expectations regarding toxicity under treatment.

Comparative effectiveness of intensity modulated radiation therapy (IMRT), proton therapy (PT), and conformal radiation therapy (CRT) in the treatment of localized prostate cancer.

3 Background: Comparative effectiveness research is urgently needed in prostate cancer because of the rapid adoption of newer and costlier radiation treatments such as IMRT and PT despite limited demonstrated benefit compared to prior technologies. We compared the morbidity and disease control outcomes of IMRT, PT and the older CRT for primary prostate cancer treatment. METHODS Population-based study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2000 through 2009 for patients with non-metastatic prostate cancer. Propensity score adjustment was used to balance demographic, disease and institutional characteristics. Rates of morbidity (gastrointestinal, urinary, erectile dysfunction, hip fractures) and additional cancer therapy (surrogate for recurrence) were calculated. RESULTS IMRT use increased from 0.15% in 2000 to 95.9% in 2008. In propensity score-adjusted analyses, men who received IMRT vs. CRT were less likely to be diagnosed with GI morbidity (13.4 vs. 14.7 per 100 person-years, p<0.001) and hip fractures (0.8 vs. 1.0, p=0.006), but more likely to be diagnosed with erectile dysfunction (5.9 vs. 5.3, p=0.006). IMRT patients were less likely to receive additional cancer therapy (2.5 vs. 3.1, p<0.001). In a propensity-score matched comparison between PT and IMRT, PT patients had a higher rate of GI morbidity (17.8 vs. 12.2 per 100 person-years, p<.001). No significant differences in rates of other morbidities or additional therapies between PT and IMRT. CONCLUSIONS IMRT vs. CRT was associated with less GI morbidity and hip fractures, more erectile dysfunction, and less need for additional cancer therapy. This large-scale population-based study is the first to suggest a simultaneous reduction in disease recurrence and morbidity in patients treated with IMRT vs. CRT for localized prostate cancer. Proton therapy did not significantly improve outcomes compared to IMRT, but had increased GI morbidity. These results provide new and long-needed information to decision-makers regarding the currently available evidence on the comparative effectiveness of different RT techniques.