The ongoing PROTEUS study aims to evaluate the effectiveness of perioperative Apalutamide combined with androgen-deprivation therapy in improving oncological outcomes for a specifically defined high-risk prostate cancer (PCa) group who were treated with radical prostatectomy (RP). Interestingly, the PROTEUS inclusion criteria did not rely on established risk categories such as the European Association of Urology (EAU) or the National Comprehensive Cancer Network (NCCN) high-risk classification. Consequently, little is known about the natural course of patients eligible for PROTEUS who were diagnosed with high-risk PCa and treated with RP without receiving any neoadjuvant systemic treatment. To address this knowledge gap, this analysis included 701 patients eligible for PROTEUS who have undergone RP, revealing that a significant proportion did not fit into the established high-risk classifications (EAU high-risk: 58.2% and NCCN high-risk: 53.1%). Event-free survival (EFS) rates at 36 and 60 mo of the overall cohort of patients eligible for PROTEUS were 57.6% (95% confidence interval [CI]: 53.9-61.7) and 45.9% (95% CI: 41.9-50.4), respectively. Notably, patients solely eligible for PROTEUS criteria exhibited more favorable EFS rates than those who also met EAU and/or NCCN high-risk criteria. This study highlights the need to enhance treatment strategies for patients with high-risk PCa and suggests potential implications for future research based on PROTEUS data. The results aim to inform clinical practices and the understanding the natural history and its outcomes of patients eligible for PROTEUS who were diagnosed with PCa and underwent RP without neoadjuvant systemic treatment.

Abstract Purpose Currently available post-hoc TITAN study data indicate favorable cancer-control in metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with apalutamide, even in patients with high metastatic burden, such as ≥ 10 bone metastases. However, these findings have never been validated in real-world setting. Patients and methods We relied on the FRAMCAP (FRAnkfurt Metastatic Cancer database of the Prostate) and stratified apalutamide-treated mHSPC patients according to number of bone metastases (≥ 10 vs. < 10). Primary endpoints were time to metastatic castration-resistant prostate cancer (ttCRPC) and overall survival (OS). Finally, exploratory analyses were made against mHSPC treatment with abiraterone and docetaxel. Results Of 105 apalutamide-treated mHSPC patients, median age was 71 years and median PSA 46 ng/ml. In total, 23% of included patients had ≥ 10 bone metastases. Patients with ≥ 10 bone metastases harbored higher PSA level at treatment start (254 vs. 29 ng/ml) and achieved less PSA response under treatment (PSA nadir 0.64 vs. 0.03 ng/ml, both p < 0.01). Regarding ttCRPC, no statistically significant difference was observed between ≥ 10 vs. < 10 bone metastases with median ttCRPC of 32 vs. 37 months (p = 0.15). Regarding OS, median OS was significantly shorter for ≥ 10 vs. < 10 bone metastases (29 vs. 64 months, hazard ratio: 2.5, p = 0.02), even after multivariable adjustment for baseline patient and tumor characteristics. In further analyses, apalutamide (32 months) showed numerically longer median ttCRPC compared to abiraterone (18 months) and docetaxel (16 months) in patients with ≥ 10 bone metastases. Conclusion In real-world setting, apalutamide-treated mHSPC patients presenting with a high bone metastatic burden achieve virtually similar ttCRPC outcomes compared to those with a lower metastatic burden. Exploratory comparisons with other first-line doublet mHSPC treatment options indicate a potential advantage of apalutamide. Clinical trial registration Not applicable.

Objective To evaluate the diagnostic performance of different staging modalities and oncological outcomes in patients with intermediate-risk (IR) prostate cancer (PCa) undergoing radical prostatectomy (RP) with pelvic lymph node dissection (PLND).Patients and Methods Patients with IR PCa who underwent RP and PLND between 2015 and 2021 were retrospectively analysed. Patients who had received neoadjuvant hormone therapy were excluded. The effectiveness of computed tomography (CT), magnetic resonance imaging (MRI), and prostate-specific membrane antigen-positron emission tomography (PSMA-PET) in detecting lymph node invasion (LNI) was assessed. Kaplan-Meier analysis was used to evaluate biochemical recurrence-free and metastasis-free survival.Results Among 8043 patients with IR PCa undergoing RP with PLND, 624 (7.8%) had LNI. PSMA-PET was performed in 400 patients: six true positives, 40 false negatives, 14 false positives, and 340 true negatives. CT was used in 2079 patients: two true positives, 228 false negatives, seven false positives, and 1842 true negatives. MRI was performed in 148 patients: one true positive, 11 false negatives, and 136 true negatives, with no false positives. Sensitivity was highest for PSMA-PET (13%), followed by MRI (8.3%) and CT (0.9%). Negative predictive values were 92.5% for MRI, 89.5% for PSMA-PET, and 89% for CT. Patients with negative PSMA-PET findings had significantly better biochemical recurrence-free and metastasis-free survival than those with suspicious findings on PSMA-PET.Conclusions All evaluated staging modalities demonstrated limited sensitivity in detecting LNI in patients with IR PCa, including PSMA-PET. Given the poor diagnostic performance of conventional imaging, such methods may be omitted in this setting. PSMA-PET may still be considered selectively, as it provides modest sensitivity and prognostic value, although its role remains limited.

BACKGROUND:The therapeutic landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has expanded significantly with triplet regimens, raising questions about their real-world applicability. This study evaluates the efficacy and safety of darolutamide- and abiraterone-based triplets using real-world data from the ARON-3 study. METHODS:A retrospective analysis was conducted on 247 mHSPC patients treated with DARO+DOCE+ADT or ABI+DOCE+ADT across 37 institutions in 14 countries. Key outcomes included progression-free survival (PFS), overall survival (OS), PSA kinetics, and safety. A propensity score was estimated based on key clinical variables and included as a covariate in Cox regression models to adjust for baseline imbalances between treatment groups. RESULTS:Data from 247 patients receiving triplet therapy were analyzed. The median OS for the entire cohort was not reached (NR). The median PFS was 24.8 months (95% CI: 18.7-33.6), with NR for DARO+DOCE+ADT and 21.5 months (95% CI: 13.1-25.2) for ABI+DOCE+ADT (P=0.007). In patients with visceral metastases, DARO+DOCE+ADT demonstrated superior outcomes, achieving higher OS rates at 6 months (97% vs. 83%, P=0.002) and 12 months (92% vs. 74%, P<0.001) compared to ABI+DOCE+ADT. The safety profiles of both regimens were comparable, although grade 3-4 fatigue was more frequently observed in the ABI+DOCE+ADT group. After adjusting for baseline imbalances through propensity score inclusion in multivariate models, the differences in OS (P=0.103) and PFS (P=0.135) between treatment groups did not reach statistical significance, although a numerical trend favoring DARO+DOCE+ADT was observed. CONCLUSIONS:Both regimens demonstrate efficacy, with DARO+DOCE+ADT offering superior outcomes in high-volume disease, especially visceral metastases. Nonetheless, the limited sample size and potential biases highlight the need for further follow-up and biomarker-driven studies in larger cohorts to refine treatment strategies.

To assess the diagnostic performance, predictors, and clinical utility of MRI-guided prostate biopsy over an 18 year period in a real-world tertiary care setting. We retrospectively analyzed patients who underwent MRI-guided prostate biopsy between 2006 and 2024 at a German tertiary care center. Clinical data, PI-RADS, PSA levels, prostate volume, and biopsy outcomes were evaluated. Logistic regression models assessed associations between clinical variables and cancer detection, clinical significance (ISUP ≥ 3), and upgrading after radical prostatectomy (RPE). Among 496 patients (mean age 66 ± 8 years; PSA, median (IQR): 7.2 ng/ml (5–10)), cancer was detected in 33

Cancer-specific mortality (CSM) rates in patients with rare histological prostate cancer subtypes after treatment with radical prostatectomy (RP) versus radiation therapy (RT) are largely unknown. Relying on the Surveillance, Epidemiology, and End Results database (2004–2020), we identified patients with five prostate cancer subtypes treated with RP or RT. Kaplan–Meier analyses and Cox regression models addressed CSM. Of 427,055 patients, 425,692 (99.68

Background and objective:Local treatment (LT) to the prostate demonstrated better cancer-control outcomes in combination with androgen deprivation therapy (ADT) monotherapy for patients with low-volume metastatic hormone sensitive prostate cancer (mHSPC). However, the association of LT with outcomes in patients receiving ADT plus androgen receptor pathway inhibitors (ARPI) across different mHSPC subtypes is under debate. Methods:Relying on the multicentric international ARON-3 database, patients with de novo low-volume mHSPC undergoing ARPI treatment were selected. Stratification was made according to LT vs. no LT with the primary endpoint of time on treatment (ToT) and overall survival (OS). Key findings and limitations:Of 454 patients with de novo low-volume mHSPC, LT was administered in addition to ARPI in 18%. In the 6-mo landmark cohort, ToT was longer in patients who received additional LT, although the association did not reach statistical significance (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.27-1.10, p = 0.088). The restricted mean survival time (RMST) at 36 mo reported a difference of 2.76 mo (95% CI: 0.32-6.58, p = 0.031) in the LT group compared with the no-LT group. OS was significantly longer in patients receiving ARPI and LT compared with ARPI alone (HR: 0.09, 95% CI: 0.01-0.64, p = 0.016). The RMST at 36 mo reported a difference of 4.67 mo (95% CI: 3.18-6.17, p < 0.001) in favor of the LT group. In the ridge regression, LT remained the only statistically significant predictor of ToT and OS. Conclusions and clinical implications:The current study suggests that adding LT to ARPIs in patients with de novo low-volume mHSPC may be associated with improved ToT and OS. The addition of LT to ARPI as the backbone of therapy may be considered in patients presenting with de novo low-volume mHSPC.

Introduction Most patients with metastatic hormone-sensitive prostate cancer (mHSPC) are burdened by bone metastases. However, the impact of concomitant distant lymph node metastases at diagnosis in these patients is unknown. Materials and methods We relied on a single-center retrospective mHSPC patient cohort treated between 2014 and 2024 to compare time to metastatic castration-resistant prostate cancer (mCRPC) and overall survival (OS) between M1b vs. M1a + b mHSPC patients. Univariable and multivariable Cox regression models were applied. Results Among 432 patients, 64% harbored M1b vs. 36% M1a + b mHSPC. Median PSA was numerically higher (82 vs. 46 ng/ml, p = 0.2) and rates of LATITUDE high-risk (76% vs. 55%) and CHAARTED high-volume disease (70% vs. 50%) were significantly higher in the M1a + b group (both p < 0.001). Regarding time to mCRPC, median time to CRPC was 26 vs. 16 months for M1b vs. M1a + b patients (hazard ratio [HR]: 1.6, p < 0.01). Regarding OS, median OS was not significantly different, with median OS of 53 vs. 47 months for M1b vs. M1a + b patients (p = 0.9). After controlling for patient and tumor characteristics in multivariable Cox regression analyses, concomitant lymph node metastases were not an independent risk for shorter time to CRPC or OS in patients with bone metastases (both p > 0.15). Conclusion Patients with concomitant distant lymph node metastases in mHSPC with bone metastases (M1a + b) harbor more unfavorable baseline cancer characteristics relative to M1b without lymph node metastases, translating into significantly shorter time to mCRPC. However, after controlling for patient and tumor characteristics, neither time to mCRPC nor OS seems not be affected by concomitant lymph node metastases.

Objective To externally validate the Martini-Klinik nomogram based on patient and clinical tumor characteristics predicting the indication for adjuvant radiation therapy after radical prostatectomy according to guideline recommendations of the European Association of Urology (EAU) in high-risk prostate cancer patients treated with radical prostatectomy. Methods Relying on a tertiary-care database, we identified high-risk prostate cancer patients treated with radical prostatectomy (01/2014-12/2024). External validation was assessed in terms of accuracy, calibration and net benefit, using decision curve analyses. Results Of 404 high-risk prostate cancer patients, 182 (45%) had the indication for adjuvant radiation therapy according to current EAU guidelines. The nomogram predicted the outcome with 79% accuracy. A high level of agreement between the predicted and observed probability of indication for adjuvant radiation therapy was observed. Minimal overestimation from the ideal predictions were noted for predicted probabilities between 25% and 50%, as well as a minimal underestimation between the predicted probability of 0% and 20% as well as 75% and 100%. In decision curve analyses, the use of the nomogram resulted in greater net benefit for all threshold probabilities between 25% and 95%, relative to both competing strategies - none or all treated. Conclusions This external validation within a contemporary tertiary-care cohort confirmed the ability of the Martini-Klinik nomogram to predict the indication for adjuvant radiation therapy after radical prostatectomy according to current EAU guideline recommendations in high-risk prostate cancer patients. The present nomogram may support clinicians in preoperative patient counseling about the risk for adjuvant treatment.

[177Lu]Lu-PSMA-617 is a standard-of-care therapy for metastatic castration-resistant prostate cancer (mCRPC). Given the heterogeneous clinical responses, accessible prognostic tools are needed. We recently demonstrated that the Bellmunt Risk Score (BRS)—comprising ECOG performance status >0, hemoglobin <10 g/dL, and the presence of liver metastases—predicts overall survival (OS) in a primary mCRPC cohort. This study aims to externally validate the BRS in an independent cohort. We retrospectively evaluated 243 mCRPC patients treated with [177Lu]Lu-PSMA-617 at an independent tertiary center. The BRS was calculated at baseline (range 0-3). Endpoints included OS analyzed via Kaplan-Meier estimators, multivariable Cox regression, Harrell’s C-index, and time-dependent area under the curve (tAUC). The cohort was distributed into BRS 0 (17.6

OBJECTIVE:Patient and treatment stratification for metastatic hormone-sensitive prostate cancer (mHSPC) is usually based on metastatic burden according to CHAARTED criteria, classifying high-volume disease as at least 4 bone metastases, one outside the axial skeleton, or one visceral metastasis. We aimed to examine the impact of the number of bone metastases independently of CHAARTED criteria. MATERIAL AND METHODS:Using the FRAMCAP (FRAnkfurt Metastatic Cancer database of the Prostate), time to castration resistant prostate cancer (ttCRPC) and overall survival (OS) were analyzed in patients with mHSPC stratified into 1 to 3 vs. 4 to 7 vs. ≥8 bone metastases, irrespective of axial skeletal location. Comparisons were made against CHAARTED low- and high-volume mHSPC outcomes. RESULTS:Of 398 patients with mHSPC, 43% harbored 1 to 3, 19% 4 to 7 and 38% ≥8 bone metastases. CHAARTED high-volume mHSPC was diagnosed in 52%. Median ttCRPC was lowest for ≥8 bone metastases (16.2 months), followed by 4 to 7 (17.3 months) and 1 to 3 bone metastases (28.4 months; P < 0.01). Similar ttCRPC outcomes were observed when stratification was made into CHAARTED low- (28.4 months) vs. high-volume mHSPC (17.2 months). Median OS was also significantly shorter for ≥8 bone metastases (34.5 months), followed by 4 to 7 (53.3 months), and 1 to 3 (56.4 months; P < 0.001). Comparable OS outcomes were observed in CHAARTED low- (58.3 months) vs. high-volume mHSPC (43.4 months). CONCLUSION:The number of bone metastases, regardless of their localization in the axial skeleton, has a significant influence on cancer-control outcomes. Especially, patients with ≥4 bone metastases have comparable outcomes to CHAARTED high-volume patients with mHSPC with at least one metastasis outside the axial skeleton.

OBJECTIVE:Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is a novel staging modality for prostate cancer (PCa) patients with a high positive predictive value for lesions within and outside of the prostate. To assess the ability of the maximum standardized uptake value (SUVmax) at PSMA PET/CT to predict adverse pathology at radical prostatectomy (RP). MATERIAL AND METHODS:Within a high-volume center database, we identified intermediate and high-risk PCa patients who had a PSMA PET/CT with an available intraprostatic SUVmax before RP between 2016 and 2021. Logistic regression modeling was used to test for the ability of SUVmax to predict non-organ confined disease or adverse pathology (non-organ confined and/or Gleason grade group ≥3) during RP. Kaplan-Meier analyses were used to compare biochemical recurrence (BCR)-free survival after RP stratified according to SUVmax. RESULTS:Overall, 544 patients were identified. Of those, median lesional intraprostatic SUVmax was 9.5 at PSMA PET/CT. Median PSA was 8.1 ng/ml prior to RP. 50.7% vs. 49.3% had D'Amico intermediate and high-risk characteristics. Median follow-up was 24.6 months. BCR-free survival at 48 months after RP was 72.1% vs. 62.2% (p = 0.03) for patients with SUVmax <9.5 vs. SUVmax ≥9.5 at PSMA PET. In logistic regression models, SUVmax (continuously coded and stratified in <9.5 vs. ≥9.5) represented an independent predictor for non-organ confined disease and adverse pathology. CONCLUSIONS:SUVmax ≥9.5 at PSMA PET/CT is an independent predictor of adverse pathology at RP. Moreover, it is associated with worse BCR-free survival after RP.

BACKGROUND AND OBJECTIVE:Recently published data comparing the impact and duration of androgen deprivation therapy (ADT) on metastasis-free survival (MFS), progression-free survival (PFS), and overall survival (OS) in patients undergoing salvage radiation therapy (sRT) after radical prostatectomy have not been compared directly; this study aims to address this knowledge gap. METHODS:We performed a systematic review and network meta-analysis (NMA) on MFS, PFS, and OS using data from the RADICALS-HD, NRG/RTOG 9601, RTOG 0534, and GETUG-AFU 16 trials, as well as three trials from the ARTISTIC meta-analysis (GETUG-AFU 17, RADICALS-RT, and RAVES) on adjuvant versus salvage radiotherapy. The primary outcome was MFS; the secondary outcomes were PFS and OS. Stratification was made according to ADT duration (ADT for 24 mo vs ADT for 6 mo vs no ADT). Subgroup analyses addressed high-risk cohorts with Gleason score ≥8 and positive surgical margins (PSMs). KEY FINDINGS AND LIMITATIONS:Data from 3710 prostate cancer patients were analyzed. Addition of ADT to sRT improved MFS and PFS significantly, regardless of the duration, but had no significant effect on OS. Hazard ratios (HRs) for ADT for 24 mo versus no ADT were 0.70 (confidence interval [CI] 0.53-0.92) for MFS, 0.51 (CI 0.43-0.61) for PFS, and 0.80 (CI 0.63-1.01) for OS; for ADT for 6 mo versus no ADT, the respective HRs were 0.79 (CI 0.65-0.97), 0.57 (CI 0.48-0.67), and 0.93 (CI 0.72-1.20). In subgroup analyses, ADT for 24 mo was ranked highest for MFS in patients with PSMs and Gleason score ≥8. CONCLUSIONS AND CLINICAL IMPLICATIONS:The NMA supports the addition of ADT to sRT, particularly a 24-mo duration, which provides the best MFS and PFS outcomes. While OS did not improve significantly, patients with Gleason score ≥8 or PSMs also benefit from prolonged ADT.

Radium- 223 and Lutetium- 177 prostate-specific membrane antigen radioligand therapy (Lu- 177-PSMA) are approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Data on cancer-control outcomes of sequential therapy of Lu- 177-PSMA after radium- 223 are rare. Using the Frankfurt Metastatic Cancer database of the Prostate (FRAMCAP) database, we analyzed progression-free (PFS) and overall (OS) survival of patients after radium- 223 pretreatment vs. radium- 223-naïve controls undergoing Lu- 177-PSMA radioligand within 1 st- 7 th line mCRPC treatment. Of 329 Lu- 177-PSMA mCRPC patients 19

OBJECTIVE:Demographic changes will lead to higher proportions of metastatic hormone-sensitive (mHSPC) and castration resistant metastatic prostate cancer (mCRPC) patients with higher frailty index and multiple comorbidities. MATERIALS AND METHODS:We relied on an institutional tertiary-care database to explore the effect of frailty (Eastern Cooperative Oncology Group [ECOG]), as well as cardiovascular (CVD) and secondary malignancy (SecCa) comorbidities on overall survival (OS) and time to mCRPC in mHSPC and OS in mCRPC patients with Kaplan-Meyer estimates and Cox regression models. RESULTS:Of 802 mHSPC patients, 61% were ECOG0 vs. 32% ECOG1 vs. 6.5% ECOG≥2. Significant differences in baseline patient and baseline mHSPC characteristics were observed for all three groups (all P ≤ 0.05). In time to mCRPC analyses and OS analyses of mHSPC and mCRPC patients, significant disadvantages were observed for ECOG 1/≥2 patients, relative to ECOG0, even after multivariable adjustment. Moreover, 31% of included patients had history/active CVD, which yielded significant median OS differences in mHSPC patients (95 vs. 63 months, multivariable hazard ratio: HR: 1.77, P < 0.01), but not in mCRPC patients (P = 0.085). After stratification according to SecCa, 14% had a SecCa which led to significant median OS differences in mCRPC patients (50 vs. 37 months, P < 0.01) but not in mHSPC patients (76 vs. 64 months, P = 0.089). Patients with higher frailty index and comorbidities showed significant differences in therapy lines. CONCLUSION:Frailty and specific comorbidities significantly influence cancer-control outcomes in mHSPC, as well as mCRPC patients, even after controlling for adverse tumor characteristics.

BACKGROUND AND OBJECTIVE:Prostate-specific-membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is more accurate than conventional imaging for lymph node (LN) staging in prostate cancer. However, it has limitations in detecting micrometastatic lymph node invasion (LNI). Our aim was to evaluate the accuracy of PSMA PET/CT for overall and size-dependent LNI detection in contemporary patients undergoing radical prostatectomy (RP) and pelvic lymph node dissection (PLND). METHODS:Within a high-volume center database, we identified 873 patients who underwent PSMA PET/CT for primary staging before RP and PLND between 2016 and 2021. Data for lymph node status on imaging and histology results were analyzed. KEY FINDINGS AND LIMITATIONS:Of 873 patients, 25% (n = 220) had LNI. Median prostate-specific antigen was 8.3 ng/ml (interquartile range 4.3-14.3). The majority of patients had high-risk (53%) or intermediate-risk disease (45%). In the overall cohort, the per-patient sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy calculated for LNI detection via PSMA PET/CT were 45.5%, 92.6%, 67.6%, 83.4%, and 80.8%, respectively. The median metastatic LN size in the group of 120 patients with false-negative PET/CT results was 2.5 mm. For metastatic LNs ≥5 mm, the sensitivity and NPV increased to 68.8% (+23.3%) and 95.4% (+12.0%), respectively. The main limitation is the lack of central review of PSMA PET/CT scans. CONCLUSIONS AND CLINICAL IMPLICATIONS:PSMA PET/CT is accurate in the staging of pelvic LNs before RP, especially for detection of metastases in LNs with a diameter ≥5 mm.

PURPOSE: The optimal time point of salvage radiotherapy (sRT) for biochemical recurrence (BCR) following radical prostatectomy is still under debate. Current European guidelines recommend salvage intensity-modulated and image‐guided radiotherapy for men with two consecutive PSA rises. However, no specific PSA threshold for initiation time is recommended. Nonetheless, lower PSA level may be associated with better cancer-control outcomes. METHODS: Relying on the University Cancer Center Frankfurt database, we evaluated differences in metastasis-free survival (MFS) among patients treated with early sRT (< 0.5 ng/ml) vs. sRT at PSA ≥ 0.5ng/ml. Subgroup analyses addressed sRT patients with high-risk features for indication of adjuvant radiation therapy, including Gleason score 8–10 and/or pT3–4 stage and/or pN1. RESULTS: Of 190 sRT patients, 69% received early sRT at median PSA 0.24ng/ml vs. 0.89ng/ml. MFS was significantly better for early sRT patients, relative to sRT at PSA > 0.5 ng/ml (hazard ratio [HR]: 8.44, p < 0.01). Similarly, sRT patients with high-risk features also had significant better MFS at sRT with PSA < 0.5ng/ml (HR: 12.69, p < 0.01). After additional multivariable adjustment, early sRT at PSA < 0.5ng/ml was independently associated with better MFS outcomes for all patients (HR: 8.2) and high-risk sRT subgroups (HR: 55.6, both p < 0.05). Finally, we validated the initiation of sRT at an even lower cut-off of a PSA level ≤ 0.25ng/ml. However, this did not result in a significantly different outcomes, probably due to sample size limitations. CONCLUSION: Our results validate European guidelines’ recommendation to initiate sRT at low PSA levels < 0.5ng/ml providing better MFS, especially in patients with high-risk features, refusing adjuvant radiation therapy.