High-intermediate Group Research Articles

The prostate cancer risk stratification (ProCaRS) project: Recursive partitioning risk stratification analysis

BackgroundThe Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision-making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema. MethodsThe RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively. ResultsThe recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ⩽6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ⩾87.5% OR PSA >30). ConclusionsProposed RS subcategories have been identified by a RPA of the ProCaRS database.

Did GOG99 and PORTEC1 change clinical practice in the United States?

ObjectiveTo assess the practice of adjuvant radiation (RT) for endometrial cancer in the United States following the publication of the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC1), and Gynecologic Oncology Group-Adjuvant Radiation for Intermediate Risk Endometrial Cancers (GOG99). MethodsA retrospective cohort study using the NCI SEER database compared the use of RT pre and post publication of PORTEC1 (1996–99 v 2000–03) and GOG 99 (2000–03 v 2004–07). Criteria for intermediate (IR) and high-intermediate (HIR) risk categories as defined by PORTEC1 and GOG99 were applied. Chi-squared statistics and adjusted multivariable Poisson models were used. ResultsRT did not increase for HIR (RR 1.05, 95%CI 0.99, 1.11) or IR groups (RR 1.0, 95% CI 0.95, 1.05) following GOG99 publication, or for HIR (RR 1.01, 95% CI 0.86, 1.19) or IR groups (RR 0.88, 95% CI 0.77–1.00) following PORTEC1 publication. Radiation rates changed heterogeneously across the country without a discernible pattern of cause. Among radiated patients, brachytherapy use increased, whereas external beam use decreased after GOG99 publication. ConclusionsAs the debate regarding the utility of adjuvant radiation in early stage endometrial cancer continues, we found that overall, clinicians had not adopted GOG99 or PORTEC1 results into their clinical practice in the years immediately after publication. However, we did identify significant variation in practice by geographic location. Given that barely half the women deemed highest risk for recurrence received radiation, these findings illustrate that clinical practice reflects the continued controversy surrounding adjuvant radiation in the treatment of endometrial cancer.

Expanded risk groups help determine which prostate radiotherapy sub-group may benefit from adjuvant androgen deprivation therapy.

PurposeTo assess whether an expanded (five level) risk stratification system can be used to identify the sub-group of intermediate risk patients with prostate cancer who benefit from combining androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT).Materials and methodsUsing a previously validated 5-risk group schema, a prospective non-randomized data set of 1423 men treated at the British Columbia Cancer Agency was assessed for the primary end point of biochemical control (bNED) with the RTOG-ASTRO "Phoenix" definition (lowest PSA to date + 2 ng/mL), both with and without adjuvant ADT. The median follow-up was 5 years.ResultsThere was no bNED benefit for ADT in the low or low intermediate groups but there was a statistically significant bNED benefit in the high intermediate, high and extreme risk groups. The 5-year bNED rates with and without ADT were 70% and 73% respectively for the low intermediate group (p = non-significant) and 72% and 58% respectively for the high intermediate group (p = 0.002).ConclusionThere appears to be no advantage to ADT where the Gleason score is 6 or less and PSA is 15 or less. ADT is beneficial in patients treated to standard dose radiation with Gleason 6 disease and a PSA greater than 15 or where the Gleason score is 7 or higher.

CHOP Versus CHOP Plus ESHAP and High-Dose Therapy with Autologous Peripheral Blood Progenitor Cell Transplantation for High-Intermediate–Risk and High-Risk Aggressive Non-Hodgkin's Lymphoma

The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%–57% in CHOP vs. 43%, 95% CI: 23%–65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%–58% vs. 15%, 95% CI: 4%–32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%–98% vs. 37%, 95% CI: 7%–69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%–70% for ESHAP/HDT vs. 30%, 95% CI: 13%–48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%–39% for ESHAP/HDT vs. 8%, 95% CI: 1%–26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL.

Standing on Your Own Feet

The Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision-making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema.The RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively.The recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ⩽6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ⩾87.5% OR PSA >30).Proposed RS subcategories have been identified by a RPA of the ProCaRS database.