Proton therapy for the management of localized prostate cancer: Long-term clinical outcomes at a comprehensive cancer center.

BACKGROUND AND PURPOSE: Proton therapy (PT) has emerged as a standard-of-care treatment option for localized prostate cancer at our comprehensive cancer center. However, there are few large-scale analyses examining the long-term clinical outcomes. Therefore, this article aims to evaluate the long-term effectiveness and toxicity of PT in patients with localized prostate cancer. MATERIALS AND METHODS: Review of 2772 patients treated from May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 850]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 116]. Biochemical failure and toxicity were analyzed using Kaplan-Meier estimates and multivariate models. RESULTS: The median patient age was 66 years; the median follow-up time was 7.0 years. Pelvic lymph node irradiation was prescribed to 28 patients (1%) (2 [0.2%] U-IR, 11 [3.5%] HR, and 15 [12.9%] VHR). The median dose was 78 Gy in 1.8-2.0 Gy(RBE) fractions. Freedom from biochemical relapse (FFBR) rates at 5 years and 10 years were 98.2% and 96.8% for the LR group; 98.3% and 93.6%, F-IR; 94.2% and 90.2%, U-IR; 94.3% and 85.2%, HR; and 86.1% and 68.5%, VHR. Two patients died of prostate cancer. Overall rates of late grade ≥ 3 GU and GI toxicity were 0.87% and 1.01%. CONCLUSIONS: Proton therapy for localized prostate cancer demonstrated excellent clinical outcomes in this large cohort, even among higher-risk groups with historically poor outcomes despite aggressive therapy.

Implementation of hypofractionated prostate radiation therapy in the United States: A National Cancer Database analysis.

PURPOSE: Preclinical and clinical research over the past several decades suggests that hypofractionated (HFxn) radiation therapy schedules produce similar treatment outcomes compared with conventionally fractionated (CFxn) radiation therapy for definitive treatment of localized prostate cancer (PCa). We sought to evaluate national trends and identify factors associated with HFxn utilization using the US National Cancer Database. METHODS AND MATERIALS: We queried the National Cancer Database for men diagnosed with localized (N0,M0) PCa from 2004 through 2013 treated with external beam radiation therapy. Patients were grouped by dose per fraction (DpF) in Gray: CFxn was defined as DpF ≤2.0, moderate HFxn as DpF >2.0 but <5.0, and extreme HFxn as DpF ≥5.0. Men receiving DpF <1.5 or >15.0 were excluded, as were those receiving <25 or >90 Gy total dose. Multiple logistic regression was performed to identify demographic, clinical, and treatment factor associations. RESULTS: A total of 132,403 men were identified, with 120,055 receiving CFxn, 7264 moderate HFxn, and 5084 extreme HFxn. Although CFxn was by far the most common approach over the analysis period, HFxn use increased from 6.2% in 2004 to 14.2% in 2013 (P < .01). Extreme HFxn use increased the most (from 0.3% to 8.5%), whereas moderate HFxn utilization was unchanged (from 5.9% to 5.7%). HFxn use was independently associated with younger age, later year of diagnosis, non-black race, non-Medicaid insurance, non-Western residence, higher income, academic treatment facility, greater distance from treatment facility, low-risk disease group (by National Comprehensive Cancer Network criteria), and nonreceipt of hormone therapy. CONCLUSIONS: Although CFxn remains the most common radiation therapy schedule for localized PCa, use of HFxn appears to be increasing in the United States as a result of increased extreme HFxn use. Financial and logistical factors may accelerate adoption of shorter schedules. Considering the multiple demographic and prognostic differences identified between these groups, randomized outcome data comparing extreme HFxn to alternatives are desirable.

Patient characterization and usage trends of proton beam therapy for localized prostate cancer in the United States: A study of the National Cancer Database.

PURPOSE: To evaluate usage trends and identify factors associated with proton beam therapy (PBT) compared to alternative forms of external beam radiation therapy (RT) (EBRT) for localized prostate cancer. PATIENTS AND METHODS: The National Cancer Database was queried for men with localized (N0, M0) prostate cancer diagnosed between 2004 and 2013, treated with EBRT, with available data on EBRT modality (photon vs. PBT). Binary multiple logistic regression identified variables associated with EBRT modality. RESULTS: In total, 143,702 patients were evaluated with relatively few men receiving PBT (5,709 [4.0%]). Significant differences in patient and clinical characteristics were identified between those men treated with PBT compared to those treated with photon (odds ratio [OR]; 95% CI). Patients treated with PBT were generally younger (OR = 0.73; CI: 0.67-0.82), National Comprehensive Cancer Network low-risk compared to intermediate (0.71; 0.65-0.78) or high (0.44; 0.38-0.5) risk, white vs. black race (0.66; 0.58-0.77), with less comorbidity (Charlson-Deyo 0 vs. 2+; 0.70; 0.50-0.98), live in higher income counties (1.55; 1.36-1.78), and live in metropolitan areas compared to urban (0.21; 0.18-0.23) or rural (0.14; 0.10-0.19) areas. Most patients treated with PBT travelled more than 100 miles to the treatment facility. Annual PBT utilization significantly increased in both total number and percentage of EBRT over time (2.7%-5.6%; P<0.001). PBT utilization increased mostly in men classified as National Comprehensive Cancer Network low-risk (4%-10.2%). CONCLUSION: PBT for men with localized prostate cancer significantly increased in the United States from 2004 to 2013. Significant demographic and prognostic differences between those men treated with photons and protons were identified.

Proton Beam Therapy for Localized Prostate Cancer: Results from a Prospective Quality-of-Life Trial.

PURPOSE: To report prostate cancer outcomes, toxicity, and quality of life (QOL) in men treated with proton beam therapy (PBT). PATIENTS AND METHODS: Patients were enrolled in a prospective trial. All participants received 75.6 to 78 Gy (RBE). Up to 6 months of luteinizing hormone-releasing hormone agonist therapy was allowed. The Phoenix definition defined biochemical failure. Modified Radiation Therapy Oncology Group criteria defined toxicity. Expanded Prostate Cancer Index Composite questionnaires objectified QOL. Clinically significant QOL decrement was defined as ≥0.5 × baseline standard deviation. RESULTS: In total, 423 men were analyzed. The National Comprehensive Cancer Network risk classification was used (low 43%; intermediate 56%; high 1%). At the 5.2-year median follow-up, overall and disease-specific survival rates were 99.8% and 100%, respectively. Cumulative biochemical failure rate was 5.2% (95% confidence interval [CI] = 3.0%-8.3%); acute grade 2 genitourinary (GU) toxicity was 46.3%; acute grade 2 gastrointestinal (GI) toxicity was 5.0% (95% CI = 3.1%-7.3%). There was no acute grade ≥3 GI or GU toxicity. Cumulative late grade 2 GU and GI toxicity was 15.9% (95% CI = 13%-20%) and 9.7% (95% CI = 6.5%-12%), respectively. There were 2 grade 3 late GI toxicities (rectal bleeding) and no late grade ≥3 GU toxicity. The 4-year mean Expanded Prostate Cancer Index Composite urinary, bowel, sexual, and hormonal summary scores (range; standard deviation) were 89.7 (43.8-100; 11), 91.3 (41.1-94.6; 10), 57.8 (0.0-96.2; 27.1), and 92.2 (25-95.5; 10.5), respectively. Compared with baseline, there was no clinically significant decrement in urinary, sexual, or hormonal QOL after treatment completion. A modest (<10 points), yet clinically significant, decrement in bowel QOL was appreciated throughout follow-up. CONCLUSION: Contemporary PBT resulted in excellent biochemical control, minimal risk of higher-grade toxicity, and modest QOL decrement. Further investigation comparing PBT with alternative prostate cancer treatment strategies are warranted.

Prostate cancer-specific mortality after definitive radiation therapy: who dies of disease?

BACKGROUND: A competing risks analysis was undertaken to identify subgroups at greatest risk of dying from prostate cancer (PC) after definitive external beam radiation therapy (RT)±androgen deprivation therapy (ADT) in the prostate specific antigen (PSA) era. METHODS: Outcomes of 2675 men with localised PC treated with RT±ADT from 1987-2007 were analysed. Prostate cancer-specific mortality (PCSM) and non-PCSM rates were calculated after stratifying patients according to National Comprehensive Cancer Network (NCCN) risk-group, RT dose, use of ADT and age at treatment. RESULTS: Only 0.2% of low-risk men died of PC 10 years after treatment. All of these deaths occurred in patients treated with < 72 Gy, and only one patient ≥ 70 years old who received ≥ 72 Gy died of PC at last follow-up. Likewise, none of the patients with intermediate-risk disease treated with ≥ 72 Gy and ADT died of PC at 10 years, and the highest 10-year rate of PCSM was seen in men ≥ 70 years old treated with < 72 Gy without ADT (5.1%). Among high-risk men < 70 years old, treatment with RT dose < 72 Gy without ADT yielded similar 10-year rates of PCSM (15.2%) and non-PCSM (18.5%), whereas men treated with ≥ 72 Gy and ADT were twice as likely to die from other causes (16.2%) than PC (9.4%). In high-risk men ≥ 70 years old, dose-escalation with ADT reduced 10-year PCSM from 14% to 4%, and most deaths were due to other causes. CONCLUSION: Low- and intermediate-risk patients treated with definitive RT are unlikely to die of PC. PCSM is higher in men with high-risk disease but may be reduced with dose-escalation and ADT, although patients are still twice as likely to die of other causes.

Sexual function and the use of medical devices or drugs to optimize potency after prostate brachytherapy.

PURPOSE: Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. METHODS AND MATERIALS: Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. RESULTS: At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. CONCLUSIONS: Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry.

Improvement in prostate cancer survival over time: a 20-year analysis.

PURPOSE: This study aimed to evaluate the changes in outcome for men with localized prostate cancer treated with definitive external beam radiation therapy during a 20-year period at a comprehensive cancer center. METHODS: We categorized 2675 men with prostate cancer treated at MD Anderson Cancer Center with definitive external beam radiation therapy with or without androgen deprivation therapy into 3 treatment eras: 1987 to 1993 (n = 722), 1994 to 1999 (n = 828), and 2000 to 2007 (n = 1125). To help adjust for stage migration, patients were stratified according to risk group as defined by the National Comprehensive Cancer Network. Biochemical (Phoenix definition), local, distant, and any clinical failure, prostate-cancer specific survival, and overall survival were analyzed according to the Kaplan-Meier method. RESULTS: Median age was 68.5 years and median follow-up was 6.4 years. Fewer men in the most recent era had high-risk disease, and a higher proportion received 72 Gy or higher (99% vs 4%) and androgen deprivation therapy (60% vs 6%) than the earliest era. All risk groups treated in the modern era experienced improved rates of biochemical, local, and distant failure. In high-risk patients, decreased rates of distant failure and clinical failure led to improved prostate cancer-specific survival and overall survival. Local control was improved for intermediate- and high-risk patients, with a trend toward improvement in low-risk patients. On multivariate analysis, recent treatment era was closely correlated with a dose of 72 Gy or higher and treatment with androgen deprivation therapy and predicted for lower rates of biochemical, local, and distant failure. Androgen deprivation therapy, higher dose, and more recent treatment era predicted for improved prostate cancer-specific survival. DISCUSSION: During the last 20 years of prostate cancer irradiation, disease control outcomes have improved in all patients, leading to improved prostate cancer-specific survival and overall survival for men with high-risk disease. This may reflect advances in workup, staging accuracy, and prostate cancer treatment in the modern era.

Microcystic adnexal carcinoma of the face treated with radiation therapy: a case report and review of the literature.

BACKGROUND: Microcystic adnexal carcinoma is a rare, locally aggressive neoplasm most commonly occurring on the face. Minimal data are available regarding the role of radiation therapy (RT). METHODS: Cases treated with RT from 2 comprehensive cancer centers are reviewed along with a review of the literature. RESULTS: Three patients with microcystic adnexal carcinoma of the face were treated with curative intent. One patient received RT as monotherapy. Two patients received postoperative RT (PORT). The patient receiving RT as monotherapy experienced excellent clinical regression, had an in-field recurrence at 48-month follow-up, and is now without evidence of disease after reirradiation. Both patients receiving PORT are without evidence of disease. CONCLUSION: PORT may improve local control in patients with microcystic adnexal carcinoma, and its use should be considered in patients with high-risk features for local recurrence. RT as monotherapy should be considered when poor cosmetic outcome can be anticipated via standard surgical treatments.