Locoregional Prostate Cancer Research Articles

Volumetric Modulated Arc Therapy for High-Risk and Very High-Risk Locoregional Prostate Cancer in the Modern Era: Real-World Experience from an Asian Cohort.

This study retrospectively evaluates the clinical outcomes of definitive volumetric modulated arc therapy (VMAT) for high-risk or very high-risk locoregional prostate cancer patients from an Asian institution. Consecutive patients who received VMAT (76 Gy in 38 fractions) between January 2017 and June 2022 were included. Whole pelvic radiotherapy (WPRT) (46 Gy in 23 fractions) was employed for clinically node-negative disease (cN0) and a Roach estimated risk of ≥15%, as well as simultaneous integrated boost (SIB) of 55-57.5 Gy to node-positive (cN1) disease. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints included radiographic relapse-free survival (RRFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCSS). A total of 209 patients were identified. After a median follow-up of 47.5 months, the 4-year actuarial BRFS, RRFS, MFS and PCSS were 85.2%, 96.8%, 96.8% and 100%, respectively. The incidence of late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 15.8% and 11.0%, respectively. No significant difference in cancer outcomes or toxicity was observed between WPRT and prostate-only radiotherapy for cN0 patients. SIB to the involved nodes did not result in increased toxicity. International Society of Urological Pathology (ISUP) group 5 and cN1 stage were associated with worse RRFS (p < 0.05). PSMA PET-CT compared to conventional imaging staging was associated with better BRFS in patients with ISUP grade group 5 (p = 0.039). Five-year local experience demonstrates excellent clinical outcomes. PSMA PET-CT staging for high-grade disease and tailored pelvic irradiation based on nodal risk should be considered to maximize clinical benefit.

GD2 and its biosynthetic enzyme GD3 synthase promote tumorigenesis in prostate cancer by regulating cancer stem cell behavior

While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel targetable pathways that contribute to tumor progression in PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblastoma, but the role of GD2 in PC is unexplored. Here, we show that GD2 is expressed in a small subpopulation of PC cells in a subset of patients and a higher proportion of metastatic tumors. Variable levels of cell surface GD2 expression were seen on many PC cell lines, and the expression was highly upregulated by experimental induction of lineage progression or enzalutamide resistance in CRPC cell models. GD2high cell fraction was enriched upon growth of PC cells as tumorspheres and GD2high fraction was enriched in tumorsphere-forming ability. CRISPR-Cas9 knockout (KO) of the rate-limiting GD2 biosynthetic enzyme GD3 Synthase (GD3S) in GD2high CRPC cell models markedly impaired the in vitro oncogenic traits and growth as bone-implanted xenograft tumors and reduced the cancer stem cell and epithelial-mesenchymal transition marker expression. Our results support the potential role of GD3S and its product GD2 in promoting PC tumorigenesis by maintaining cancer stem cells and suggest the potential for GD2 targeting in advanced PC.

Testosterone replacement therapy (TRT) in patients with locoregional prostate cancer (LPC) treated with prior androgen deprivation therapy (ADT): A single center review.

e24045 Background: In LPC, ADT may be combined with radiation therapy (RT) for 4-24 months. Post-ADT, a significant proportion of men experience prolonged hypogonadism. TRT can alleviate symptoms and improve metabolic outcomes. Contrary to longstanding concerns, there is no substantial evidence of increased prostate cancer recurrence in patients (pts) treated with single modalities (surgery or RT). However, sparse data ( &lt; 100 cases published to our knowledge) exist regarding recurrence risk of LPC with TRT after prior ADT, where baseline T levels may fall below the androgen receptor saturation point. Methods: We retrospectively abstracted clinical data from hospital records of men with stage I – IVA PC, treated with prior concurrent ADT and RT and subsequently received TRT between January 2014 and September 2023. Extracted data included demographics, cancer diagnosis/staging, ADT/TRT treatment details and PSA and clinical outcomes. The co-primary endpoints were change in PSA and incidence of PC recurrence. Results: 21 pts met criteria. Median age was 77. ISUP Grade Groups (GG) included: GG1: 2, GG2: 2, GG3: 8, GG4: 2, and GG5: 7. AJCC 8th ed. stages were: I: 2, II: 7, III: 7, IV-A: 5. The median duration of prior ADT was 8 months (IQR 5 – 17) and the median interval from RT to TRT was 19 months (IQR: 12 – 44). Prior to TRT, the median testosterone level was 30.5 ng/dL (IQR: 17-76). TRT formulations included: injection: 6, oral: 4, topical: 13. The median follow-up period from the start of TRT was 13 months, and the median duration on TRT was 10 months (IQR: 5-22). TRT was ongoing in 15 (71.4%) pts and discontinued in 6 (28.6%). Reasons for discontinuation included testosterone recovery (1), hospice (not PC related) (2), no perceived benefit (2), MD concern for PSA rise (1). After TRT, the median testosterone level was 336 ng/dL (IQR: 207-462). Median PSA pre- and post-TRT were undetectable and 0.08 ng/dL, respectively. None of the subjects experienced PC recurrence or PC-specific mortality. One pt showed PSA bounce without recurrence. Median BMI was unchanged before (28.3 kg/m2) and after (27.7 kg/m2) TRT (p = 0.48). Due to the nature of the study, quality of life measures and metabolic parameters could not be systematically abstracted. Conclusions: In men with LPC who remained hypogonadal long-term after prior ADT and RT, we found that TRT was not associated with a significant rise in median PSA and no cases of PC recurrence were documented. This included many with a history of very high-risk cancers (eg. GG ≥ 4, Stage ≥ III). This study adds to the sparse existing literature in this clinical setting and together they support the case for a prospective trial utilizing TRT in patients who remain hypogonadal after ADT and radiation.

Prospective clinical sequencing of 1016 Chinese prostate cancer patients: uncovering genomic characterization and race disparity.

Although there is a well-known disparity in prostate cancer (PC) incidence and mortality between Chinese and Western patients, the underlying genomic differences have been investigated only sparsely. This clinicogenomic study was conducted to reveal the genomic mutations contributing to the PC disparity across ethnicities and investigate the mutational profile of Chinese PC patients. A total of 1016 Chinese PC patients were prospectively enrolled and subjected to targeted sequencing, resulting in usable sequencing data for 41 genes from 859 patients. Genomic data retrieved from The Cancer Genome Atlas (TCGA; locoregional PC), Memorial Sloan Kettering Cancer Center [MSKCC; metastatic castration-sensitive PC (mCSPC)], and Stand Up To Cancer [SU2C; metastatic castration-resistant PC (mCRPC)] cohorts were used as comparators representing Western men. Genomic mutations were analyzed using an integrated bioinformatic strategy. A comparison of the disease stages revealed that mutations in tumor protein 53 (TP53), androgen receptor (AR), forkhead box A1 (FOXA1), and genes involved in the cell cycle pathway were enriched in mCRPC. Mutations in adenomatous polyposis coli (APC) gene were found to be more prevalent in patients with visceral metastasis. Genomic differences between Western and Chinese men were mainly observed in castration-sensitive PC, with tumors from Chinese men having more FOXA1 (11.4% vs. 4.2%) but fewer TP53 (4.8% vs. 13%) mutations in locoregional PC and harboring fewer TP53 (11% vs. 29.2%), phosphatase and tensin homolog (PTEN; 2.5% vs. 10.3%), and APC (1.7% vs. 7.4%) mutations in the mCSPC stage than those of Western men. Patients of both ethnicities with mCRPC had similar mutational spectra. Furthermore, FOXA1 class-2 was less common than FOXA1 class-1 and showed no enrichment in metastasis, contrary to the findings in the Western cohort. Our study provides a valuable resource for a better understanding of PC in China and reveals the genomic alterations associated with PC disparity across races.

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer.

Maximum tumor diameter (MTD) on pretreatment magnetic resonance imaging (MRI) has the potential to further risk stratify for men with prostate cancer (PCa) prior to definitive local therapy. We aim to evaluate the prognostic impact of radiographic maximum tumor diameter (MTD) in men with localized prostate cancer. From a single-center retrospective cohort of men receiving definitive treatment for PCa (radical prostatectomy [RP] or radiotherapy [RT]) with available pretreatment MRI, we conducted univariable and multivariable Cox proportional-hazards models for progression using clinical variables including age, NCCN risk group, radiographic extracapsular extension (ECE), radiographic seminal vesical invasion (SVI), and MTD. RP and RT cohorts were analyzed separately. Covariates were used in a classification and regression tree (CART) analysis and progression-free survival was estimated with the Kaplan-Meier method and groups were compared using log-rank tests. The cohort included 631 patients (n=428 RP, n=203 RT). CART analysis identified 4 prognostic groups for patients treated with RP and 2 prognostic groups in those treated with RT. In the RP cohort, NCCN low/intermediate risk group patients with MTD>=15 mm had significantly worse PFS than those with MTD <= 14 mm, and NCCN high-risk patients with radiographic ECE had significantly worse PFS than those without ECE. In the RT cohort, PFS was significantly worse in the cohort with MTD >= 23 mm than those <= 22 mm. Radiographic MTD may be a useful prognostic factor for patients with locoregional prostate cancer. This is the first study to illustrate that the importance of pretreatment tumor size may vary based on treatment modality.

Relationships between erectile dysfunction, prostate cancer treatment type and inflatable penile prosthesis implantation.

PurposeThe prevalence of erectile dysfunction (ED) and the utilization of inflatable penile prosthesis (IPP) among prostate cancer patients are understudied. The aim of the study was to examine the relationships between ED, prostate cancer treatment type and IPP implantation in a national cohort.Materials and MethodsWe identified a retrospective cohort of Surveillance, Epidemiology, and End Results (SEER)-Medicare patients diagnosed with locoregional prostate cancer between 2006 and 2011 and treated with surgery or radiation. Chi-square tests were used to detect significant differences in ED rates as well as use of IPP among the subset with ED. Multivariable logistic regression was used to examine factors associated with the use of IPP.ResultsAmong 31,233 patients in our cohort, 10,334 (33.1%) received prostatectomy and 20,899 (66.9%) received radiation. ED within 5 years was significantly more common in the prostatectomy group relative to those the radiation group (65.3% vs. 33.8%, p<0.001). In the subset of 13,812 patients with ED, the radiation group had greater median time to ED diagnosis compared to the prostatectomy group (346 vs. 133 days, p<0.001). IPP implantation was more frequent for prostatectomy patients than for radiation patients (3.6% vs. 1.4%, p<0.001). Cancer treatment type, race, and marital status were significantly associated with IPP utilization.ConclusionsED is highly prevalent among prostate cancer patients, and IPP implantation is be underutilized. ED rates, time to ED diagnosis and utilization of IPP differed significantly by prostate cancer treatment type.

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer

Feasibility and Oncologic Outcome of Salvage Surgery in Isolated Seminal Vesicle Remnants after Radical Prostatectomy

Background: To demonstrate the feasibility of resecting isolated locally relapsing seminal vesicle remnants after primary radical prostatectomy and radiotherapy. Early oncologic outcomes and prognostic risk factors for relapse are demonstrated. Objectives and Methods: A total of 32 patients underwent open resection of locoregional prostate cancer recurrence in seminal vesicles, as documented on either MRI, ¹¹C-choline, or ⁶⁸Ga-PSMA PET/CT scans. Age, PSA-DT, PSA, and time to recurrence after primary treatment resection status were used in a uni- and multivariate Cox regression analysis for biochemical relapse after surgery. Results: Median patient age at time of salvage surgery was 70 (57–77) years. Median PSA and PSA-DT was 2.79 (0.4–61.54) ng/mL and 5.4 (1.6–20.1) months, respectively. Median surgical time and hospital stay was 132 (75–313) min and 5.5 (4–13) days, respectively. After a mean follow-up of 29 (2–92) months, 3 patients died at 8, 14, and 40 months after salvage surgery, and 6 (18.75%) patients remain without biochemical relapse and further treatment. Median progression-free survival was 12 (1–81) months. In the univariable Cox regression analysis, age at time of surgery, preoperative PSA, and the time from primary treatment to salvage surgery were identified as significant parameters for biochemical relapse. Only the interval from primary to salvage surgery was significant in the multivariate analysis with a hazard ratio of 1.008 (95% CI: 1.001–1.015, p = 0.018). In the entire cohort, 4 adjunctive surgeries (3 ureteroneocystostomies and 1 nephrectomy) were needed due to local progressive disease. Conclusion: Seminal vesicle resection is feasible with no significant intra- or postoperative complications. Almost all patients progressed to biochemical or systemic relapse. Salvage surgery must be seen as a preventive for local symptoms, in our experience most often postrenal ipsilateral obstruction.

Preoperative 68Ga-PSMA PET/CT defines a subgroup of high-risk prostate cancer patients with favorable outcomes after radical prostatectomy and lymph node dissection.

High-risk prostate cancer is associated with adverse pathology and unfavorable outcomes after radical prostatectomy. 68Ga-PSMA PET/CT is more accurate than conventional imaging for preoperative staging. We aimed to evaluate whether lymph node involvement on 68Ga-PSMA PET/CT prior to radical prostatectomy in patients with high-risk prostate cancer is associated with worse short-term oncologic outcomes. We retrospectively reviewed 149 patients with high-risk localized or locoregional prostate cancer who underwent 68Ga-PSMA PET/CT prior to radical prostatectomy between 2015 and 2020. None of the patients received neoadjuvant or adjuvant treatment. The study endpoints were PSA persistence and biochemical recurrence. Logistic regression models were used to identify preoperative predictors of PSA persistence. Kaplan-Meier analyses were used to estimate biochemical recurrence-free survival. Of 149 identified patients, 19 (13%) were found to have lymph node involvement on preoperative 68Ga-PSMA PET/CT. The sensitivity, specificity, and accuracy of 68Ga-PSMA PET/CT for identifying pathologic lymph node involvement were 68%, 95%, and 92%, respectively. PSA persistence rate was lower among patients with PET-negative lymph nodes than those with PET-positive nodes (15 vs. 84%, p < 0.001). Positive nodes on imaging (OR = 41.03, p < 0.001) and clinical T2c-T3 stage (OR = 6.96, p = 0.002) were associated with PSA persistence on multivariable analysis. Among patients with PET-negative nodes the 1- and 2-year biochemical recurrence-free survival rates were 87% and 76%, respectively. Preoperative staging with 68Ga-PSMA PET/CT may identify a subgroup of high-risk prostate cancer patients with favorable short-term outcomes after radical prostatectomy without adjuvant treatment. Future studies will evaluate whether these results are sustained during long-term follow-up.

Physician and facility drivers of spending variation in locoregional prostate cancer.

Prostate cancer is the most common male cancer, with a wide range of treatment options. Payment reform to reduce unnecessary spending variation is an important strategy for reducing waste, but its magnitude and drivers within prostate cancer are unknown. In total, 38,971 men aged ≥66years with localized prostate cancer who were enrolled in Medicare fee-for-service and were included in the Surveillance, Epidemiology, and End Results-Medicare database from 2009 to 2014 were included. Multilevel linear regression with physician and facility random effects was used to examine the contributions of urologists, radiation oncologists, and their affiliated facilities to variation in total patient spending in the year after diagnosis within geographic region. The authors assessed whether spending variation was driven by patient characteristics, disease risk, or treatments. Physicians and facilities were sorted into quintiles of adjusted patient-level spending, and differences between those that were high-spending and low-spending were examined. Substantial variation in spending was driven by physician and facility factors. Differences in cancer treatment modalities drove more variation across physicians than differences in patient and disease characteristics (72% vs 2% for urologists, 20% vs 18% for radiation oncologists). The highest spending physicians spent 46% more than the lowest and had more imaging tests, inpatient care, and radiotherapy spending. There were no differences across spending quintiles in the use of robotic surgery by urologists or the use of brachytherapy by radiation oncologists. Significant differences were observed for patients with similar demographics and disease characteristics. This variation across both physicians and facilities suggests that efforts to reduce unnecessary spending must address decision making at both levels.

Contemporary Incidence and Outcomes of Prostate Cancer Lymph Node Metastases

The incidence of localized prostate cancer has decreased with shifts in prostate cancer screening. While recent population based studies demonstrated a stable incidence of locoregional prostate cancer, they categorized organ confined, extraprostatic and lymph node positive disease together. However, to our knowledge the contemporary incidence of prostate cancer with pelvic lymph node metastases remains unknown. We used SEER (Surveillance, Epidemiology and End Results) data from 2004 to 2014 to identify men diagnosed with prostate cancer. We analyzed trends in the age standardized prostate cancer incidence by stage. The impact of disease extent on mortality was assessed by adjusted Cox proportional hazard analysis. During the study period the annual incidence of nonmetastatic prostate cancer decreased from 5,119.1 to 2,931.9 per million men (IR 0.57, 95% CI 0.56-0.58, p <0.01) while the incidence of pelvic lymph node metastases increased from 54.1 to 79.5 per million men (IR 1.47, 95% CI 1.33-1.62, p <0.01). The incidence of distant metastases in men 75 years old or older reached a nadir in 2011 compared to 2004 (IR 0.81, 95% CI 0.74-0.90, p <0.01) and it increased in 2012 compared to 2011 (IR 1.13, 95% CI 1.02-1.24, p <0.05). The risk of cancer specific mortality significantly increased in men diagnosed with pelvic lymph node metastases (HR 4.5, 95% CI 4.2-4.9, p <0.01) and distant metastases (HR 21.9, 95% CI 21.2-22.7, p <0.01) compared to men with nonmetastatic disease. The incidence of pelvic lymph node metastases is increasing coincident with a decline in the detection of localized disease. Whether this portends an increase in the burden of advanced disease or simply reflects decreased lead time remains unclear. However, this should be monitored closely as the increase in N1 disease reflects an increase in incurable prostate cancer at diagnosis.

Variation in Locoregional Prostate Cancer Care and Treatment Trends at Commission on Cancer Designated Facilities: A National Cancer Data Base Analysis 2004 to 2013.

Contemporary treatment trends for prostate cancer show increased rates of active surveillance. However, nationwide applicability of these reports is limited. Additionally, the effect of Commission on Cancer facility type on prostate cancer treatment patterns is unknown. We used the National Cancer Data Base to identify men diagnosed with prostate cancer, between 2004 and 2013. Our cohort was stratified on the basis of the National Comprehensive Cancer Network prostate cancer risk classes. Cochran-Armitage tests were used to evaluate temporal trends. Random effects hierarchical logit models were used to assess treatment variation at Commission on Cancer facility and institution level. In 825,707 men, utilization of radiation therapy declined and utilization of radical prostatectomy increased for all prostate cancer risk groups between 2004 and 2013 (P< .0001). Observation for low-risk prostate cancer increased from 16.3% in 2004 to 2005 to 32.0% in 2012 to 2013 (P< .0001). Significant treatment variation was observed on the basis of Commission on Cancer facility type. Across all risk groups, the lowest rates of radical prostatectomy and highest rates of external beam radiation therapy were observed in community cancer programs. The highest rates of observation for low-risk disease were observed in academic centers. Treatment variation according to institution ranged from 14% (95% confidence interval, 0.12-0.15) for androgen deprivation therapy up to 59% (95% confidence interval, 0.45-0.73) for cryotherapy. The increased utilization of observation in low-risk prostate cancer is an encouraging finding, which appears to be mainly derived by a decrease in radiotherapy utilization in this risk group. Regardless of tumor characteristics, significant variations in treatment modality exist among different facility types and institutions.

The impact of subsequent metastasis on survival in Medicare patients with prostate cancer.

94 Background: This study assessed the impact of subsequent metastasis on survival in Medicare prostate cancer (PC) patients initially diagnosed with locoregional disease. Methods: Using data from the United States Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims, we identified patients diagnosed with locoregional PC between 2000 and 2011, age ≥ 66 at diagnosis, and who first had a diagnosis of metastasis ≥ 4 months after PC diagnosis (cases). Cases were matched to controls (patients without metastasis) in a 1:4 ratio to assess the incremental impact of developing metastasis. For each control, the timeline to develop metastasis was matched to the cases. Kaplan-Meier (K-M) analysis was used to compare all-cause, cancer-specific, and other-cause mortality between cases and controls. Cox proportional hazards regression was used to adjust for other factors associated with all-cause mortality. Results: There were 10,370 cases and 39,200 controls. Mean age at baseline was 79 years in each group. Among the cases, the median time to first metastasis was 37 months, 85% had bone metastasis, and the median survival time (months) after metastasis was 18 months compared to 118 months for controls (P &lt; 0.0001: Log-Rank). In K-M analysis, metastasis was associated with significantly (P &lt; 0.0001: Log-Rank) higher all-cause, cancer-related, and other-cause mortality. In multivariable survival analysis, metastasis was associated with increased all-cause mortality (HR = 4.6, 95% CI = 4.4-4.7, P &lt; 0.0001). High risk disease (based on Gleason score, comorbidity Index, and performance status) and delayed diagnosis of metastases were associated with worse survival. Conclusions: Development of metastasis in elderly PC patients diagnosed with locoregional disease significantly increases mortality.

Planning of External Beam Radiotherapy for Prostate Cancer Guided by PET/CT.

In this paper, we give an overview of articles on non-choline tracers for PET/CT for patients with prostate cancer and planning of radiotherapy guided by PET/CT. Nineteen articles described (11)C-Acetate PET/CT. Of 629 patients 483 (77%, 95% CI 74% - 80%) had positive (11)C-Acetate PET/CT scans. Five articles described (18)F-FACBC PET/CT. Of 174 patients, 127 (73%, 95% CI 68% - 78%) had positive scans. Both tracers detected local lesions, lesions in regional lymph nodes, and distant organs. Ten articles described (18)F-NaF PET/CT and found that 1289 of 3918 patients (33%) had positive reactive lesions in bones. PET/CT scan can guide external beam radiotherapy (EBRT) planning for patients with loco-regional prostate cancer. In six studies with 178 patients with localized prostate cancer, PET/CT pointed out dominant intraprostatic lesions (DIL). Oncologists gave EBRT to the whole prostate and a simultaneously integrated boost to the DIL. Four studies with 254 patients described planning of EBRT for patients with PETpositive lymph nodes. After the EBRT, 15 of 29 node-positive patients remained in remission for median 28 months (range 14 to 50 months). Most articles describe (11)C- and (18)F-Choline PET/CT. However, (11)C-Acetate and (18)F-FACBC may also be useful tracers for PET/CT. Planning of radiotherapy guided by MRI or PET/CT is an investigational method for localized prostate cancer. Current clinical controlled trials evaluate whether the method improves overall survival.

Association between urologist characteristics and radiation oncologist consultation for patients with locoregional prostate cancer.

Physicians managing patients with prostate cancer play a critical role in subsequent specialist consultations and initial treatment choice, especially in cases for which no consensus exists regarding optimal treatment strategy. The NCCN Guidelines for Prostate Cancer recommend radiation as a therapy option for patients with locoregional prostate cancer. The authors examined the association of urologist characteristics with the likelihood that patients would consult radiation oncologists. A retrospective cohort of 39,934 patients aged 66 years or older who were diagnosed with locoregional prostate cancer between 2004 and 2007, and the 2405 urologists who performed the patient diagnostic biopsies were constructed using the SEER-Medicare linked database and the American Medical Association Physician Masterfile. Logistic multilevel regression analysis was used to evaluate the influence of urologists' characteristics on radiation oncologist consultation within 9 months of locoregional prostate cancer diagnosis. Overall, 24,549 (61.5%) patients consulted a radiation oncologist. After adjusting for patient and urologist characteristics, patients diagnosed by urologists in noninstitutional settings (eg, physician office) were significantly more likely to consult a radiation oncologist (odds ratio [OR], 1.40; 95% CI, 1.17-1.67; P=.0002) compared with those diagnosed by urologists in institutional settings with a major medical school affiliation. In addition, patients diagnosed by urologists older than 57 years were significantly more likely to consult a radiation oncologist (OR, 1.21; 95% CI, 1.07-1.38, P=.003).

Locoregional prostate cancer treatment pattern variation in independent cancer centers: policy effect, patient preference, or physician incentive?

Surveillance, Epidemiologic, and End Results (SEER) registry data abstracted from a priority 2 or higher reporting source from 2006 to 2008 were used to compare treatment patterns in 45–64-year old men diagnosed with locoregional prostate cancer (LRPC) across states with or without radiation therapy-directed certificate of need (CON) laws and across independent cancer centers (ICCs) compared to large multi-specialty groups (LMSGs). Adjusted treatment percentages for the five most common LRPC treatments (surgery, external beam radiation therapy (EBRT), combination brachytherapy with EBRT, brachytherapy, and observation) were compared using cross-sectional logistic regression between CON-unregulated and -regulated states and between LMSGs and ICCs. LRPC EBRT rates were no different across CON regions, but are increased in ICCs compared to LMSGs (37.00% vs. 13.23%, P < 0.001). Variation in LRPC treatment patterns by reporting source merits further scrutiny under the Affordable Care Act of 2010, considering the intent of incentivized accountable care organizations (ACOs) established by the Patient Protection and Affordable Care Act of 2010 (PPACA) and the implications of early descriptions of these new healthcare provider organizations on prostate cancer treatment patterns.

Risk Of Acute and Chronic Leukemias Following Radiation Treatment For Locoregional Prostate Cancer In The United States Over 35-Years

▪ BackgroundProstate cancer is the most common cancer diagnosis in men, and one of the leading indications for radiation therapy. The risk of resultant secondary leukemias has not been consistently established. We investigated the risk of all leukemias in a population-based cohort of patients (pts) with locoregional prostate cancer definitively treated with radiotherapy. MethodsWe queried the Surveillance, Epidemiology, and End Results (SEER) 17 registries to identify a cohort of men >20 years old (n = 183,268) with locoregional prostate adenocarcinoma newly diagnosed between January 1973 and December 2008. Pts who underwent initial treatment with radical prostatectomy (RP) were compared to pts receiving RP with external beam radiotherapy (RP w/EBRT) to investigate the risk of radiation-induced leukemias. These cohorts tend to be well matched regarding age, medical comorbidities and disease characteristics. All new leukemias occurring as a second primary cancer at least one year after the first diagnosis of prostate cancer were identified in SEER using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) morphology codes. Secondary leukemias included acute myeloid leukemia (AML); chronic myelogenous leukemia (CML); acute and chronic lymphocytic leukemia (ALL & CLL) and other categories as reported in SEER. Pts were observed from date of prostate cancer diagnosis until leukemia occurrence, death, or last date of follow-up. Univariate and multivariate analyses were performed using the Fine and Gray competing risk regression analysis with leukemia as a time-dependent endpoint and death from any cause or the diagnosis of any other second cancer as competing events. RP w/ EBRT group was compared with the RP cohort as the reference group, controlling for age. Hazard ratios (HR) with 95% confidence intervals (CIs) are reported. ResultsMedian age was 67 years (yrs, range 22 – 105) at prostate cancer diagnosis: 67 yrs in RP and 68 yrs in RP w/ EBRT pts (p<0.0001); 158,913 (86.7%) were treated with RP and 24,355 (13.3%) with RP w/EBRT. Median follow-up was 7.6 yrs [(range, 1 – 35.5): 7.5 yrs in the RP group and 8.3 yrs in the RP w/ EBRT group, (p<0.0001)].In total, 949 (0.5%) leukemia cases were identified: 336 (0.2%) acute leukemias [266 (0.2%) in the RP group and 70 (0.3%) in the RP w/ EBRT]; 538 (0.3%) chronic leukemias [462 (0.3%) in the RP group and 76 (0.3%) in the RP w/ EBRT] and 75 (0.04%) of unspecified histology. Histologic subtypes (per ICD-O-3 codes) were: AML (n=249), acute monocytic leukemia (n=18), ALL (n=24), other acute leukemias (n=45), other myeloid/monocytic/lymphocytic leukemias (n=48), aleukemic/subleukemic/NOS (n=27), CML (n=131) and CLL (n=407).Median age at acute leukemia diagnosis was 77 yrs [(range, 50 – 101): 78 yrs in the RP group and 76 yrs in RP w/EBRT pts, (p=0.0271)] and for chronic leukemias was 76 yrs [(range, 47 – 101): 76 yrs in the RP group and 77 yrs in the RP w/EBRT pts, (p=0.50)].The median time to develop acute leukemias was 6.0 yrs [(range, 1 – 28.2): 6.1 yrs in the RP group and 5.7 yrs in the RP w/EBRT pts, (p=0.20)] and chronic leukemias was 6.9 yrs [(range, 1 – 29.8): 6.7 yrs in the RP group and 8.6 yrs in the RP w/EBRT pts, (p=0.0020)]. The cumulative incidence rate (CIR) at 20 years for acute leukemias was 0.24% for the RP pts vs. 0.32% for the RP w/EBRT pts (p=0.0196). The CIR at 20 years for chronic leukemias was 0.47% for the RP pts vs. 0.36% for the RP w/EBRT pts (p=0.10).In univariate analyses, age >70 yrs (HR=1.40; CI, 1.13 – 1.74; p=0.0023), and those who received RP w/ EBRT (HR=1.49; CI, 1.14 – 1.94; p=0.0033) were significantly more likely to develop acute leukemias. In multivariate analysis, both advanced age (HR=1.40; CI, 1.13 – 1.74; p = 0.0023) and RP w/ EBRT (HR=1.49; CI, 1.14 – 1.94; p=0.0032), remained significantly associated with increased risk of acute leukemias. Radiation treatment was not significantly associated with the risk of developing chronic leukemias among pts treated with RP w/EBRT vs. RP [HR=0.91; CI, 0.72 – 1.16; p=0.45). ConclusionsAmong the best matched prostate cancer treatment cohorts, those who underwent EBRT following RP had a 49% increased risk of subsequent acute leukemias, although the absolute number of cases was low. Risk assessment in this cohort spans a time frame where radiation technologies have rapidly advanced and hence treatment period effects need to be considered in interpretation of results Disclosures:No relevant conflicts of interest to declare.

The Role of the Urologist in Whether Locoregional Prostate Cancer Patients Consult With a Radiation Oncologist

Multiple treatment options exist for prostate cancer patients, and therapeutic recommendations may differ depending on characteristics of the specialist consulted. The clinical judgment of specialists who advise patients can play a critical role in the initial treatment choice, especially in cases where there is no professional consensus regarding the optimal treatment strategy. We examined the association between the medical school affiliation of a prostate cancer patient's urologist and the likelihood the patient would consult a radiation oncologist. Using the Surveillance, Epidemiology and End Results–Medicare linked database and the American Medical Association Physician Masterfile, we conducted a retrospective cohort study of 39,915 patients aged 66 years or older who were diagnosed between 2004 and 2007 with locoregional prostate cancer, and the 2,404 urologists who performed the patients’ diagnostic biopsies. Multilevel regression analysis was used to evaluate the influence of patients’ urologists’ practice affiliations with medical schools on the patients’ consultation with a radiation oncologist within 9 months of diagnosis. Overall, 25,110 (62.9%) patients consulted with a radiation oncologist. After adjusting for patient, tumor and urologist characteristics, patients who saw urologists practicing within non-institutional settings were significantly more likely to consult with a radiation oncologist (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.05-1.34, p = 0.006) when compared to those who saw urologists practicing within settings with a major medical school affiliation. In addition, patients who saw urologists aged 58 years or older were significantly more likely to consult with a radiation oncologist (OR, 1.71; 95% CI, 1.16-2.50, p = 0.006) when compared to those who saw urologists younger than 43 years old. Locoregional prostate cancer patients who received their diagnostic biopsy by urologists practicing in non-institutional settings and those who saw older urologists were significantly more likely to eventually consult with a radiation oncologist. This may have implications on which patient eventually receives radiation as initial therapy.

Role of the urologist in whether locoregional prostate cancer patients consult with a radiation oncologist.

e16029 Background: Multiple treatment options exist for prostate cancer patients, and therapeutic recommendations may differ depending on characteristics of the specialist consulted. The clinical judgment of specialists can play a critical role in the initial treatment choice, especially in cases where there is no professional consensus regarding the optimal treatment strategy. We examined the association between prostate cancer patients’ urologists’ practice affiliation with medical schools on the likelihood the patient would consult a radiation oncologist. Methods: Using the Surveillance, Epidemiology and End Results – Medicare linked database and the American Medical Association Physician Masterfile, we conducted a retrospective cohort study of 39,915 patients aged 66 years or older who were diagnosed between 2004 - 2007 with locoregional prostate cancer, and the 2,404 urologists who performed the diagnostic biopsies. Multilevel regression analysis was used to evaluate the influence of patients’ urologists’ practice affiliations with medical schools on the patients’ consultation with a radiation oncologist within 9 months of diagnosis. Results: Overall, 25,110 (62.9%) patients consulted with a radiation oncologist. After adjusting for patient, tumor and urologist characteristics, patients who saw urologists practicing within non-institutional settings were significantly more likely to consult with a radiation oncologist (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.05-1.34, p = 0.006) when compared to those who saw urologists practicing within settings with a major medical school affiliation. In addition, patients who saw urologists ≥ 58 years old were significantly more likely to consult with a radiation oncologist (OR, 1.71; 95% CI, 1.16-2.50, p = 0.006) when compared to those who saw urologists &lt; 43 years old. Conclusions: Locoregional prostate cancer patients who received their diagnostic biopsy by urologists practicing in non-institutional settings and those who saw older urologists were significantly more likely to eventually consult with a radiation oncologist. This may have implications on which patient eventually receives radiation as initial therapy.

The impact of technology diffusion on treatment for prostate cancer.

5044 Background: Robotic prostatectomy and intensity modulated radiotherapy (IMRT) hold the promise of improving cancer control and minimizing side-effects for patients with prostate cancer, but are associated with significant upfront investments. Many worry that the perceived advantages of these new technologies and the need to recoup start-up costs could shift decision making in favor of local therapy in lieu of expectant management. In this context, we examined the association of market-level technology penetration with receipt of local therapy. Methods: We used the Surveillance Epidemiology and End Results (SEER) - Medicare linked database to identify all patients with loco-regional prostate cancer who were treated or managed expectantly from 2003 to 2007 (n=59,241). We measured technology penetration as the number of providers performing robotic prostatectomy or IMRT per population in a market (hospital referral region). We then performed multinomial logistic regression to examine the association of technology penetration with receipt of prostatectomy, radiotherapy, or no local therapy. Results: For each 1,000 patients diagnosed with prostate cancer, 171 underwent prostatectomy, 493 radiotherapy, and 336 had no local therapy. Markets with high robotic prostatectomy penetration had higher use of prostatectomy (175 vs. 141 per 1,000 men, p=0.004) but decreased use of radiotherapy (584 vs. 613 per 1,000 men, p=0.046), resulting in a stable rate of local therapy (Table). High versus low IMRT penetration did not significantly impact use of prostatectomy and radiotherapy (Table). Conclusions: Increased penetration of robotic surgical technology was associated with more use of prostatectomy and less use of radiotherapy. However, increased penetration of both robotic prostatectomy and IMRT did not change the overall rate of local therapy. Our findings allay concerns that new technology spurs additional local therapy of prostate cancer. [Table: see text]