LDR-Brachytherapy monotherapy appears unsuited for NCCN unfavorable intermediate-risk prostate cancer patients.

BACKGROUND: To validate the subdivision of intermediate-risk (IR) prostate cancer (PCa) into favorable intermediate-risk (FIR) and unfavorable intermediate-risk (UIR) PCa in a historical patient cohort and to compare 2 different radiotherapy regimens. METHODS: Patients with intermediate-risk (IR) PCa, treated either by 125J-LDR-brachytherapy monotherapy (BT) or by combined-modality radiation therapy (CRT), were retrospectively subclassified into FIR and UIR and reanalyzed with regard to biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and prostate cancer-specific survival (CSS). Kaplan-Meier product-limit method and log-rank tests were applied to estimate survival probabilities and compare survival, respectively. Uni- and multivariable analyses were performed using Cox proportional hazard regression. RESULTS: Of 490 IR patients, 252 had received BT (86.5% FIR, 13.5% UIR), and 238 had received CRT (30% FIR, 70% UIR). Retrospective analysis revealed that BRFS at 10 years was 81% for BT, and 94% for CRT in FIR patients. For UIR patients, BRFS at 10 years was 37% for BT, and 89% for CRT. MFS at 10 years for FIR patients was 87% for BT, and 94% for CRT. For UIR patients MFS at 10 years was 78% for BT, and 95% for CRT. In multivariable analysis treatment (BT vs. CRT) was the single associated factor for biochemical recurrence, and for metastases in the UIR group (BFRS, P < 0.001, HR 16.07 (CI 4.23-61.10); MFS, P = 0.011, HR 8.43 (CI 1.62-43.9). CONCLUSIONS: Subclassification of IR prostate cancer into FIR and UIR subcategories appears mandatory. For FIR patients, outcomes after BT monotherapy were acceptable. However, clinical failure after 125J-LDR-BT in UIR patients was notably increased, suggesting that BT monotherapy was less successful in this risk group. In contrast, the outcome in UIR patients after CRT was excellent.

Definitions of "Cure" After Low-Dose-Rate Brachytherapy in Low- and Intermediate-Risk Prostate Cancer: Phoenix or Surgical?

Purpose: The aim of this study was to compare a surgical with a Phoenix-derived definition of cure at 4 years after treatment by 125J low-dose-rate brachytherapy (LDR-BT) in patients with low- and intermediate-risk prostate cancer. Methods and Materials: A total of 427 evaluable men with low-risk (62.8%) and intermediate-risk (37.2%) prostate cancer were treated with LDR-BT (160 Gy). Cure was defined at 4 years either as not having experienced a biochemical recurrence by the Phoenix definition, or by a surgical definition, using a posttreatment prostate-specific antigen of ≤0.2 ng/mL. Biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and cancer-specific survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard diagnostic test evaluations were used to compare both definitions with regard to later metastatic failure or cancer-specific death. Results: At 48 months, 427 patients were evaluable with a Phoenix-defined and 327 with a surgical-defined cure. At 5 and 10 years BRFS was 97.4% and 89% and MFS was 99.5% and 96.3% in the Phoenix-defined cure cohort, and BRFS was 98.2% and 92.7% and MFS was 100% and 99.4% in the surgical-defined cure cohort. Specificity for cure was 100% for both definitions. Sensitivity was 97.4% for the Phoenix and 96.3% for the surgical definition. The positive predictive value was 100% for both, whereas the negative predictive value was 29% for the Phoenix and 7.7% for the surgical definition. Accuracies of a correct prediction of cure were 94.8% and 96.3% for the Phoenix and the surgical definition, respectively. Conclusions: Both definitions are useful for a reliable assessment of cure after LDR-BT in patients with low-risk and intermediate-risk prostate cancer. Cured patients might follow a less stringent follow-up schedule from 4 years onward, whereas patients not achieving cure at 4 years should be monitored for an extended time.

Comparison of outcome endpoints in intermediate- and high-risk prostate cancer after combined-modality radiotherapy.

PURPOSE: To compare a standard radio-oncological and a surgical biochemical failure definition after combined-modality radiation therapy (CRT) in men with intermediate- and high-risk prostate cancer. METHODS: 425 men were treated with external beam radiotherapy (59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Biochemical recurrence (BR) was defined either as radio-oncologic (rBR), using a +2 ng/mL prostate-specific antigen (PSA) increase above a nadir value, or as surgical (sBR), using a 2-year posttreatment PSA of ≥0.2 ng/mL. Biochemical recurrence-free, metastasis-free, cancer-specific, and overall survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard validation tests were used to compare both thresholds. RESULTS: After a median of 7 years, overall recurrence rates were 10.4% and 31.5% for rBR and sBR definitions, respectively. Both failure definitions proved sensitive for the prediction of metastases and cancer-specific death, whereas the rBR definition was significantly more specific. The accuracies of a correct prediction of metastases and death of prostate cancer were 73.1% vs. 96.2% and 72.2% vs. 92.9% for sBR vs. rBR, respectively. The inferior validity results of the sBR definition were attributable to a PSA-bounce phenomenon occurring in 56% of patients with sBR. Still, using the less suitable sBR definition, the results of CRT compared favorably to BRFS rates of surgical interventions. CONCLUSION: After CRT, the radio-oncological (aka Phoenix) failure definition is more reliable than a fixed surgical endpoint. Exclusively in high-risk patients, sBR offers a direct comparison across surgical and nonsurgical treatment options at 5 and 10 years.