Login to Access Video or Poster Abstract: MP20-02
Sources of Funding: Department of Veterans Affairs and NIH K24 CA160653

Introduction

Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions and inform patient prognosis. However, significant heterogeneity remains, especially among those with high risk disease, and thus improved stratification is needed.

Methods

Data on 3335 men, including 605 high risk, undergoing radical prostatectomy without adjuvant treatment were collected in the SEARCH database. Patients were grouped into five categories: low risk (biopsy Gleason 2-6, T1a-T2a, and PSA <10ng/ml), favorable intermediate risk (FIR), unfavorable intermediate risk (UIR), standard high risk (SHR), very high risk (VHR). Intermediate risk patients by NCCN guidelines (T2b or T2c, biopsy Gleason 7, or PSA 10-20ng/ml) were UIR if they had biopsy Gleason 4+3, ≥50% positive biopsy cores, or multiple intermediate-risk factors (T2b or T2c, biopsy Gleason 7, or PSA 10-20ng/ml), and FIR otherwise. High risk patients by NCCN guidelines (biopsy Gleason score 8-10, T3-T4, or PSA ≥20ng/ml) were VHR if they had primary Gleason 5, >50% positive biopsy cores, T3b-T4 or multiple high-risk factors (biopsy Gleason score 8-10, T3-T4, or PSA ≥20ng/ml), and SHR otherwise. Cox models were used to test the association between risk group and time to biochemical recurrence (BCR) and distant metastases (DM). Competing risks was used to test the association between risk group and prostate cancer-specific mortality (PCSM). Models were adjusted for age, race, year, and surgical center.

Results

Median follow-up was 78 mo. Men with VHR disease had increased risk of BCR (p<0.001), DM (P=0.004), and PCSM (P=0.011) in comparison to SHR, but there were no differences in BCR, DM, or PCSM between SHR and UIR patients (p>0.4). FIR men had increased risk of BCR (HR 1.34, p=0.006) and DM (HR 2.42, p=0.035) compared to low risk men, but there was no difference in PCSM (p=0.17). Therefore, we propose a novel risk grouping: Group 1 (low risk), Group 2 (FIR), Group 3 (UIR and SHR), and Group 4 (VHR). These groups have markedly different outcomes, with 10 year DM rates of 0.7%, 2.8%, 6.9%, and 16.3% (p<0.001) for Groups 1-4 respectively, and 10 year PCSM of 0.3%, 1.9%, 3.3%, and 10.9% (P<0.001). The c-index of this grouping was 0.80 for DM vs. 0.76 for D'Amico risk groups.

Conclusions

Patients classified as VHR have increased rates of PSA relapse, DM, and PCSM in comparison to SHR patients, whereas UIR and SHR patients have similar prognosis. Novel therapeutic strategies are needed for patients with VHR, likely involving multimodality therapy.

Funding

Department of Veterans Affairs and NIH K24 CA160653