Significant increase in prostatectomy and decrease in radiation for clinical T3 prostate cancer from 1998 to 2012

We aimed to describe changes in treatment patterns for clinical T3 prostate cancer (PCa) from 1998 to 2012, specifically investigating what factors influence receipt of prostatectomy or radiation. Using the Surveillance, Epidemiology, and End Results database, we studied 11,604 men with clinical T3N0M0 PCa from 1998 to 2012, with treatment categorized as radiation, radical prostatectomy (RP), or no curative therapy. We calculated rate of treatment type by year of diagnosis to investigate trends in treatment patterns, further stratifying by clinical T3a, defined as unilateral and bilateral extracapsular extension (n = 3,842), vs. T3b (defined as extension to seminal vesicles (n = 3,665). Finally, a multivariable logistic regression analysis measured association of demographic and clinical variables with type of treatment received for years 2010 to 2011. Rates of prostatectomy increased significantly from 1998 to 2012 (12.5% vs. 44.4%), radiation decreased significantly (55.8% vs. 38.4%), and receipt of no treatment also decreased (31.7% vs. 17.2%, all P<0.001). These trends were similar for clinical T3a and T3b. Rates of prostatectomy surpassed radiation by 2008 in clinical T3a, reaching 49.8% vs. 37.1%, respectively, in 2012 (P = 0.002), and were statistically similar to radiation in 2012 for clinical T3b, reaching 41.6% vs. 42.1% (P = 0.92). Multivariable logistic regression analysis demonstrated that patients were less likely to receive prostatectomy than radiation if biopsy Gleason scores of 8 to 10 (adjusted odds ratio [AOR] = 0.41, 0.32-0.53), higher initial prostate-specific antigen (AOR = 0.97, 0.97-0.98), and older age (AOR = 0.92, 0.90-0.03, all P<0.01). The likelihood of RP was similar among cT3b vs. cT3a (AOR = 0.95, 0.71-1.26, P = 0.74). Since 1998, there has been a significant increase in the use of RP for clinical T3 PCa and a significant decrease in the use of radiation such that in 2012, the use of prostatectomy exceeded the use of radiation

Receipt of definitive therapy in elderly patients with unfavorable‐risk prostate cancer

BACKGROUND Conservative management of aggressive prostate cancer in the elderly without definitive therapy has been associated with a 10‐year prostate cancer‐specific mortality of approximately 50%. The authors examined the prevalence of definitive therapy in elderly patients with intermediate‐risk or high‐risk disease. METHODS 411,343 patients who were diagnosed from 2004 through 2012 with intermediate‐risk or high‐risk prostate cancer were identified in the National Cancer Database. Multivariable logistic regression adjusting for sociodemographic characteristics and comorbidity was used to examine the association between age and receipt of definitive therapy, defined as radical prostatectomy or radiotherapy, and of primary androgen deprivation therapy (ADT) among patients who did not receive definitive therapy. RESULTS In total, 87.1% of high‐risk patients and 91.9% of intermediate‐risk patients received definitive therapy. When stratified by age, 93.7%, 92.1%, 90.8%, 87.6%, 80.9%, and 55.2% of high‐risk patients and 96.1%, 94.7%, 93.4%, 89.7%, 82.7%, and 62.8% of intermediate‐risk patients ages <60, 60 to 64, 65 to 69, 70 to 74, 75 to 79, and ≥80 years received definitive therapy, respectively. For both high‐risk and intermediate‐risk patients, increasing age was significantly associated with a decreased likelihood of receiving definitive therapy overall (both P < .001) and a greater likelihood of receiving primary ADT among those who did not receive definitive therapy (both P < .001). CONCLUSIONS Older age was significantly associated with a decreased likelihood of receiving definitive therapy and an increased likelihood of receiving primary ADT in this national cohort of patients with intermediate‐risk or high‐risk prostate cancer. Notably, approximately 40% to 45% of patients aged ≥80 years did not receive definitive therapy. These findings are alarming given the dismal outcomes of conservatively managed unfavorable‐risk prostate cancer. Cancer 2017;123:4832‐40. © 2017 American Cancer Society. In a national cohort of patients with intermediate‐risk or high‐risk prostate cancer, age is significantly associated with decreased receipt of definitive therapy. 40% to 45% of patients aged 80 years and older do not receive definitive therapy despite a high risk of cancer‐specific mortality from the conservative management of aggressive prostate cancer

Occult High-risk Disease in Clinically Low-risk Prostate Cancer with ≥50% Positive Biopsy Cores: Should National Guidelines Stop Calling Them Low Risk?

To identify contemporary, clinically low-risk patients with ≥50% cores positive and compare the risk of upgrading at prostatectomy with other low- or intermediate-risk patients. We studied 14,902 patients with prostate cancer in the Surveillance, Epidemiology, and End Results database in 2010-2011 treated with prostatectomy. Patients were categorized by National Comprehensive Cancer Network clinical risk groups, separating low-risk patients by percent positive biopsy cores (PBC). We measured incidence of pathologic high-risk disease, defined as pT3a-T4 or Gleason 8-10, and multivariable logistic regression was used to determine if patients with clinical low-risk disease and ≥50% PBC were similar to other low- or intermediate-risk patients. This analysis was repeated with favorable and unfavorable intermediate risk. At prostatectomy, 9.2% of clinically low-risk patients with <50% PBC, 18.6% of clinically low-risk patients with ≥50% PBC, and 27.6% of clinically intermediate-risk patients had occult, high-risk disease (P <.001). On multivariable logistic regression, low-risk patients with ≥50% PBC were more likely than low-risk patients with <50% PBC to have pathologic high-risk disease (adjusted odds ratio [AOR] 2.28, 95% confidence interval 1.90-2.73, P <.001), had similar risk to favorable intermediate patients overall (AOR 1.09, 0.91-1.31, P = .33), and had higher risk than favorable intermediate patients aged over 60 years (AOR 1.28, 1.00-1.64, P = .04). Low-risk patients with ≥50% PBC had a mean tumor size similar to unfavorable intermediate-risk patients (21.3 vs 21.0 mm, P = .82). Nearly 1 in 5 clinically low-risk prostate cancer patients with ≥50% PBC harbor occult pT3a-T4 or Gleason 8-10, suggesting that national guidelines should not classify low-risk patients with ≥50% cores positive as “low risk,” and patients should be made aware of this excess risk if considering active surveillance

Impact of percent positive biopsy cores on cancer-specific mortality for patients with high-risk prostate cancer

•The impact of positive biopsy cores (PBC) in high-risk prostate cancer is unclear.•We examined ≥50% PBC and prostate cancer-specific mortality (PCSM).•≥50% PBC was prognostic of a 2-fold risk of PCSM in a cohort of high-risk patients. A high percent positive biopsy cores (PBC), typically dichotomized at ≥50% is prognostic of worse cancer-specific outcomes for patients with low- and intermediate-risk prostate cancer (CaP). The clinical significance of ≥50% PBC for patients with high-risk disease is poorly understood. We examined the association between ≥50% PBC, compared to <50% PBC, and prostate cancer-specific mortality (PCSM) for patients with high-risk disease. We identified 7,569 men from the Surveillance, Epidemiology, and End Results program who were diagnosed with high-risk CaP (Gleason score of 8–10, prostate-specific antigen >20 ng/mL, or cT3-T4 stage) in 2010–2011 and had 6 to 24 cores sampled at biopsy. Multivariable Fine and Gray competing risks regression was utilized to examine the association between ≥50% PBC and PCSM. Median follow-up was 3.8 years. 56.2% of patients (4,253) had ≥50% PBC. On competing risks regression, ≥50% PBC was associated with a significantly higher risk of PCSM compared to <50% PBC (adjusted hazard ratio [AHR] 2.00, 95% confidence interval [CI] 1.48–2.70, P < 0.001). On subgroup analyses, ≥50% PBC was associated with a significantly higher risk of PCSM only for cT1–T2 disease (AHR 2.23, 95% CI 1.62–3.07) but not cT3–T4 disease (AHR 0.83, 95% CI 0.39–1.76), with a significant interaction (Pinteraction = 0.016). No significant interactions by Gleason score, prostate-specific antigen level, use of definitive therapy, or number of biopsy cores sampled were observed. In this large cohort of patients with high-risk CaP, ≥50% PBC was independently associated with an approximately 2-fold increased risk of PCSM for patients with cT1–T2, but not cT3–T4, tumors. Percent PBC, which is a widely available clinical value, should be routinely used to risk stratify men with high-risk disease and identify patients whom may benefit from treatment intensification

Factors associated with the omission of androgen deprivation therapy in radiation-managed high-risk prostate cancer

Androgen deprivation therapy (ADT) has been shown to improve survival for men with unfavorable-risk prostate cancer (PCa). We investigated the utilization and factors associated with the omission of ADT in radiation-managed high-risk PCa. We used the National Cancer Database to identify men with National Comprehensive Cancer Network high-risk PCa treated with external beam radiation therapy (EBRT) with or without brachytherapy boost from 2004 to 2012. Multivariable logistic regression adjusting for clinical and sociodemographic factors was used to identify independent predictors for ADT use. A total of 57,968 radiation-treated high-risk PCa men were included in our analysis. There were 49,363 patients (85.2%) treated with EBRT alone and 8605 patients (14.8%) treated with EBRT plus brachytherapy boost. Overall, 77% of men received ADT. In multivariable regression analysis, the use of brachytherapy boost was associated with a significantly lower utilization of ADT (70% vs. 78%; adjusted odds ratio [AOR]: 0.65; 95% CI: 0.62–0.69; p-Value <0.0001), as was treatment at an academic vs. nonacademic center (AOR: 0.90; 95% CI: 0.86–0.95; p-Value <0.0001) and treatment in 2010–2012 compared to 2004–2006 (AOR: 0.85; 95% CI: 0.81–0.90; p-Value <0.0001). Conversely, greater ADT use was seen with higher Gleason scores, PSA, and T-category (all p-Values <0.001). Approximately one in four men with radiation-managed high-risk PCa do not receive ADT, which may reflect concerns about its toxicity profile despite known improvements in overall survival. Practice patterns suggest that some providers believe dose escalation through brachytherapy boost may obviate the need for ADT in some high-risk patients, but this hypothesis requires further testing

Disparities in the Receipt of Local Treatment of Node-positive Prostate Cancer

We found that black men, those with lower incomes, older men, and those with Medicaid or no insurance had lower odds of receiving local treatment (surgery or radiation) for node-positive prostate cancer. These factors were associated with reduced overall survival; however, after adjustment for receipt of local treatment, the survival disparities associated with these factors disappeared or were reduced. We sought to determine whether any sociodemographic disparities are present in the receipt of local treatment for node-positive prostate cancer. We identified 9771 patients with clinical N1M0 prostate cancer diagnosed from 1998 to 2012 using the National Cancer Database. We used multivariable logistic regression modeling to identify patient-specific factors that were associated with a reduced likelihood of receiving prostate or pelvic radiation or radical prostatectomy. We also used Cox regression modeling to estimate the differences in overall survival (OS) using these factors. The factors associated with a reduced likelihood of receiving local therapy included black race versus white race (43.6% vs. 49.4%; adjusted odds ratio [AOR], 0.76; P = .001), bottom income quartile versus top quartile (44.7% vs. 52.7%; AOR, 0.69; P = .001), age > 66 years versus ≤ 66 years (40.8% vs. 55.1%; AOR, 0.48; P < .001), diagnosis before 2005 versus after 2005 (30.5% vs. 61.7%; AOR, 0.66; P < .001), and Medicaid or no insurance versus private insurance (41.0% vs. 49.4%; AOR, 0.41; P < .001). Although patients had reduced 5-year OS if they were from lower income quartiles (adjusted hazard ratios [AHRs], 1.18-1.22; P < .05), were older (AHR, 1.82; P < .001), or had Medicaid or no insurance (AHR, 1.24; P = .032), these disparities were no longer present or were smaller in magnitude after adjustment for receipt of local treatment. Significant treatment disparities exist in the receipt of local therapy for node-positive prostate cancer. Given the accumulating evidence supporting this practice, the factors underlying these disparities should be studied and addressed

Risk of prostate cancer mortality in men with a history of prior cancer

To describe outcomes of patients with prostate cancer diagnosed after another malignancy and identify factors associated with prostate cancer death in this population, as little is known about the clinical significance of prostate cancer as a subsequent malignancy. We studied 18 225 men diagnosed with prostate cancer after another malignancy from 1973 to 2006. We compared demographic and clinical variables, and the proportion of death from prostate cancer vs prior malignancy with t-test and chi-squared analyses. Fine and Gray's regression was used to consider the effect of treatment on prostate cancer death. We then studied a second cohort of 88 013 men with prostate cancer as a first or second malignancy to describe current diagnostic and treatment patterns. One in seven men died from prostate cancer in our first cohort. More died from prostate cancer following colorectal cancer (16.8% vs 13.7%), melanoma (13.4% vs 7.56%), and oral cancer (19.1% vs 4.04%), but fewer following bladder cancer, kidney cancer, lung cancer, leukaemia and non-Hodgkin's lymphoma (all P < 0.001). Prostate cancer treatment was associated with a nearly 50% lower risk of death when high-grade or high-stage (adjusted hazard ratio 0.55, 95% confidence interval [CI] 0.47-0.64). Patients who died from prostate cancer had higher grade and stage disease, and received less treatment than patients who died from prior malignancy. The second cohort showed subsequent prostate cancer had more high-risk disease (36.3% vs 22.2%, P < 0.001) and less prostate cancer treatment (adjusted odds ratio 0.872, 95% CI 0.818-0.930) than primary prostate cancer. Prostate cancer remains a significant cause of mortality when diagnosed as a subsequent cancer. These results suggest prostate cancer treatment should be seriously considered in patients with prior malignancies, especially those with high-grade or locally advanced prostate cancer

National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer

Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level <10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. ADT use in low-risk prostate cancer has declined nationally but may remain an issue of concern in certain populations and regions

Low rates of androgen deprivation therapy use with salvage radiation therapy in patients with prostate cancer after radical prostatectomy

The RTOG 9601 and GETUG-AFU 16 randomized controlled trials demonstrated that the addition of androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) improves progression-free and, for RTOG 9601, overall survival. We examined national trends in the use of ADT with SRT. Of the 484,009 patients in the National Cancer Database from 2004 to 2012 with localized or locally advanced prostate cancer treated with radical prostatectomy (RP), 4,200 men received SRT (≥6mo after surgery). We used Pearson’s chi-squared test to evaluate changes in ADT use, and multiple logistic regression to examine predictors of ADT use. Overall, 32.1% of SRT patients received ADT, which increased after initial results of RTOG 9601 showed an improvement in metastasis-free survival in 2010 (28.5% in 2008/2009 vs. 34.5% in 2011/2012, P = 0.006). Predictors of ADT use include presurgery prostate-specific antigen>20ng/ml vs.<10ng/ml (adjusted odds ratio [AOR] = 1.34, P = 0.002; 36.7% vs. 29.6%); positive vs. negative margins (AOR = 1.29, P = 0.001; 34.9% vs. 27.8%); Gleason 3+4 (AOR = 1.53; 21.3%), Gleason 4+3 (AOR = 2.40; 32.0%), or Gleason 8 to 10 (AOR = 4.49; 49.2%) vs. Gleason 2 to 6 (P≤0.005 for all; 13.2%); and pathologic T3a (AOR = 1.46; 30.9%), T3b (AOR = 2.50; 47.6%), or T4 (AOR = 4.14; 60.9%) vs. T2 (P<0.001 for all; 19.1%). Starting SRT 12 to 23.9 months (AOR = 0.69; 23.2%) or≥24 months (AOR = 0.25; 8.0%) after RP was associated with decreased odds of ADT use vs. starting SRT 6 to 8.9 months after RP (P≤0.002 for both; 35.0%). Although less than one-third of SRT patients from the study era received ADT, there is evidence that physicians and patients have begun slowly adopting this practice with the 2010 reporting of a decrease in the cumulative incidence of metastases with the addition of ADT to SRT. Given the newly reported survival benefit of RTOG 9601, additional work will be necessary to identify which patients benefit the most from the use of ADT with SRT to individualize treatment. •We studied trends in androgen deprivation therapy (ADT) use with salvage radiation.•From 2004 through 2012, 32.1% of salvage radiation patients received ADT.•ADT use rose to 6% with the 2010 reporting of a metastasis benefit by RTOG 9601.•Higher Gleason score, pT3–4 stage, and positive margins were predictors of ADT use