Julie A. Carlson

The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study

PURPOSE To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. METHODS AND MATERIALS The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. RESULTS A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. CONCLUSIONS In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.

The prognostic significance of Gleason scores in metastatic prostate cancer

PURPOSE Although the majority of metastatic prostate cancer (mPCa) will arise from tumors with Gleason scores (GS) of 8 to 10 existing tumor grade analyses for mPCa have been almost uniformly limited to comparisons of ≤7 vs. ≥8. In this analysis, we comprehensively evaluate the GS as a prognostic factor for mPCa in the era of the updated Gleason grading system. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with mPCa, GS 6 to 10, diagnosed from 2006 to 2008. GS and primary-secondary Gleason pattern variations were analyzed for overall survival and prostate cancer-specific survival (PCSS). RESULTS A total of 4,654 patients were evaluable. At 4 years, the overall survival rates were 51%, 45%, 34%, 25%, and 15% and PCSS rates were 69%, 57%, 44%, 33%, and 21% for GS 6, 7, 8, 9, and 10, respectively. Survival differences for GS 7 vs. 8, 8 vs. 9, and 9 vs. 10 were highly significant on both univariate and multivariate analyses accounting for age, prostate-specific antigen level, and T stage (all P<0.001). Gleason pattern 5 was an independent prognostic factor, both overall for patients with GS 6 to 10 and on primary-secondary Gleason pattern comparisons within the GS 8 (4+4 vs. 3+5 and 5+3) and GS 9 (4+5 vs. 5+4) subgroups. No survival differences were observed between 3+4 vs. 4+3. Overall, lower prostate-specific antigen level, younger age, and lower GS were associated with improved survival, with GS being the strongest prognostic factor for PCSS. CONCLUSIONS In this large population-based cohort, stratified survival outcomes were observed for GS 6 to 10, with sequential comparisons of GS 7 to 10, and the presence and extent of Gleason pattern 5 representing independent prognostic factors in the metastatic setting.

External Validation of the Benefit of Adjuvant Radiotherapy for Pathologic N1M0 Prostate Cancer

TO THE EDITOR: The recently published report by Abdolleh et al on a series of more than 1,100 patients with pN-positive prostate cancer (PCa) provides new insights into the prognostic stratification of N1M0 PCa, as well as predictive analyses to better inform patient selection for adjuvant external-beam radiotherapy (aRT). In the authors’ analysis of aRT by risk groups, patients with study-defined intermediate-risk disease (one to two positive lymph nodes, Gleason score 7, and either pT3b/pT4 or positive surgical margins) and high-risk disease (three to four positive lymph nodes) achieved improved survival with aRT in univariable and multivariable models. Conversely, patients with study-defined very low–, low-, and very high–risk disease did not seem to benefit from aRT. In an effort to validate their findings in a distinct patient population, the authors also analyzed a SEER cohort of patients with pN-positive PCa from 1999 to 2009. Similar, although not identical, risk groups were analyzed and an overall survival benefit of aRT was redemonstrated for intermediateand high-risk patients alone. However, the authors acknowledge that because of the historic conventions of data acquisition in SEER, the external validation risk groups differed from those defined in their primary analyses, as did a number of factors included in their multivariable models. Important differences included the analytic groupings for both Gleason and T stage, and the absence of surgical margin status for pT2/T3a disease, which would be necessary to properly stratify patients into low-risk versus intermediate-risk categories. Prostate-specific antigen (PSA) values were not required for study-defined risk stratifications but were accounted for in the multivariable models of the primary analysis; PSA was absent from the SEER analysis. Conversely, the authors elected to include race in the multivariable analysis of their SEER cohort but not in their primary analysis. We recently published a SEER analysis of N1M0 PCa in which we evaluated the effect of local therapy (prostatectomy, radiotherapy, or both); our analysis also demonstrated a trend toward improved overall survival in favor of the addition of aRT compared with prostatectomy alone. Given our familiarity with some of the unique features of PCa data in SEER, we were in fact able to generate identical risk stratifications as those defined in the primary analysis by Abdollah et al, and we sought to validate their findings in SEER using these identical risk groups. To provide some background information: In 2004, in a cooperative effort with the American Joint Committee on Cancer (AJCC), SEER began coding “Collaborative Stage” data, which include diagnostic PSA levels and individual Gleason scores for PCa. In addition, surgical margin status is coded specifically for patients with pT2 and pT3a PCa but not for those with pT3b or pT4 disease. Although this may be considered a rather curious approach to margin status coding, it happens to be a fortunate circumstance for our purposes, given that surgical margin status is needed only for patients with pT2/T3a PCa to inform the risk stratifications that were proposed by Abdollah et al. Therefore, by the year 2004, all data that would be required to replicate identical risk stratifications were available in SEER. In addition, all data were available to replicate multivariable analyses that are identical to those reported by Abdollah et al, with the exception of surgical margin status, which, for the reasons mentioned, could be used for risk stratification but could not be included in multivariable analyses because of a lack of data for patients with pT3b/T4 disease. Using the most recent SEER release (SEER*Stat version 8.1.5) and largest data pool (SEER 18 Registries), we searched for patients, in years overlapping those used by Abdollah et al, for which adequate

The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

PURPOSE To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. METHODS AND MATERIALS The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. RESULTS The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were observed for cause-specific survival and OS across analyses. CONCLUSIONS In this large population-based cohort, glioma histology represented a significant predictor for the survival impact of RT. Adjuvant RT was associated with improved survival for AAs, with benefits comparable to those observed for GBMs over the same 10-year interval. No survival advantage was observed with adjuvant RT for AOs.

Are We Appropriately Selecting Therapy For Patients With Cervical Cancer? Longitudinal Patterns-of-Care Analysis for Stage IB-IIB Cervical Cancer

PURPOSE We performed a patterns-of-care analysis evaluating the effects of newer technology and recent research findings on treatment decisions over 26 years to determine whether patients with cervical cancer are being appropriately selected for treatment to optimize the therapeutic ratio. METHODS AND MATERIALS A retrospective analysis was conducted using the Surveillance, Epidemiology and End Results (SEER) program from 1983 to 2009. We identified 10,933 women with stage IB-IIB cervical carcinoma. RESULTS Of the 10,933 subjects identified, 40.1% received surgery, 26.8% received radiation (RT), and 33.1% received surgery plus RT. RT use increased after 2000 compared to prior to 2000, with a corresponding decrease in surgery and surgery plus RT. Among patients with risk factors including tumor size >4 cm, positive parametria, and positive lymph nodes, declining use of surgery plus RT was observed. However, 23% of patients with tumors >4 cm, 20% of patients with positive parametria, and 55% of node-positive patients continued to receive surgery plus RT as of 2009. Factors associated with increased use of surgery plus RT included patient age <50 and node-positive status. CONCLUSIONS In this largest patterns-of-care analysis to date for patients with locally advanced cervical cancer, we found a substantial proportion of patients continue to undergo surgery followed by radiation, despite randomized data supporting the use of definitive radiation therapy, with lower morbidity than surgery and radiation.