The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer - Beyond the Abstract

As the second leading cause of cancer death in men, prostate cancer (PCa) will be diagnosed in 1 in 8 men during their lifetime.¹ National Comprehensive Cancer Network (NCCN) risk stratification for prostate cancer currently includes clinical T-stage, pre-treatment PSA level, Gleason score, lymph node involvement, and distant metastases. However, in addition to genomic classifiers, other pathologic factors in patients undergoing radical prostatectomy (RP) have been identified to be associated with oncologic outcomes, including lymphovascular invasion, margin status, and maximum tumor diameter (MTD) of the dominant prostate cancer nodule among others.^2-6

With increased access to and utilization of pretreatment MRI as part of the workup for newly diagnosed prostate cancer, additional radiographic features including MTD, seminal vesicle invasion (SVI) and extracapsular extension (ECE) can be evaluated during pretreatment.⁷ These radiographic features are not currently included in risk stratification; however, they may provide clinically useful information for identifying candidates for optimal upfront therapy due to high risk pretreatment factors.

In our study,⁸ we analyzed a cohort of 631 patients diagnosed with localized PCa with pre-treatment MRI, treated with either RP or RT at a single institution, and evaluated the impact of pretreatment MRI information on progression free survival (PFS). Through the use of a CART analysis, we identified prognostic groups for patients undergoing RP and RT. We separately analyzed the surgery and radiation groups due to different definitions of biochemical failure in each population.

The figure below (Figure 1) shows our CART Analysis for progression of disease. Note that for patients treated with surgery, MTD appeared prognostic among patients with NCCN low, favorable-intermediate, and unfavorable-intermediate risk disease when >= 15mm. Among NCCN high-risk disease, the presence of ECE on MRI was prognostic. For patients treated with radiation, MTD was prognostic regardless of NCCN risk grouping.

Figure 1, RHR = relative hazard ratio

Figure 2, below, shows progression free survival in patients treated with surgery. Groups are defined by CART analysis. Note the separation between curves by MTD size for the patients with NCCN low, favorable intermediate, or unfavorable intermediate disease. Furthermore, among NCCN high risk patients, those with radiographic ECE had the worst outcomes of any cohort. Our findings agreed with previously published work that suggested that MTD > 14mm in RP specimens was associated with increased biochemical failure, metastasis, and prostate cancer-specific mortality, independent of extracapsular extension, seminal vesicle invasion, positive surgical margins, and Gleason score.⁶

Figure 2. progression free survival in patients treated with surgery.

Lastly, Figure 3, below, shows progression free survival among patients treated with definitive radiation. Note that patients with MTD larger than 23 mm had inferior progression free survival compared to those with MTD less than 22 mm. Similarly, recently published data in the setting of brachytherapy boost demonstrated that intermediate and high-risk patients with MTD > 24mm had a 5-year biochemical failure of 31%, as compared to 4% in those with MTD<=24mm.⁹ Our study included a larger sample size of patients treated with any modality of RT including monotherapy and combination therapies.

Figure 3. progression free survival among patients treated with definitive radiation

In summary, we showed that the maximum tumor diameter was independently predictive of worse outcomes. Pretreatment MRI findings, including maximum tumor diameter, extracapsular extension, and seminal vesicle invasion are not currently included in NCCN risk stratification despite being widely available. We hope that the results of our paper will serve as motivation to further investigate MRI findings as additional prognostic factors in risk stratification.

Although our study focused on tumor size, we also included data on extracapsular extension which is particularly important for high-risk patients. Thus, MRI could be used for more reasons than just maximum tumor diameter. Radiologic findings of extracapsular extension have not previously been described as favorable or unfavorable, but in our study, NCCN high-risk patients with extracapsular extension on MRI had significantly worse progression-free survival than those without extracapsular extension.

Furthermore, our data revealed inferior oncologic outcomes in patients with larger tumors, notably in definitive radiation cohorts regardless of NCCN risk groups. This provides further justification for dose escalation efforts such as focal dose escalation to the dominant prostate nodule, as recently reported in the FLAME trial.¹⁰ As management of biochemical recurrence can cause significant toxicity and impact quality of life, improving patient selection for potential treatment escalation for upfront therapy may improve treatment efficacy and prevent the need for subsequent salvage treatments.

1. University of Utah School of Medicine, Salt Lake City, UT
2. Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT

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