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External validation of genomic classifier-based risk-stratification tool to identify candidates for adjuvant radiation therapy in patients with prostate cancer

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Abstract

Objective

To externally validate a Genomic Classifier (GC) based risk-stratification nomogram identifying candidates who would benefit from adjuvant radiation (aRT) therapy after radical prostatectomy (RP).

Methods

We identified 350 patients who underwent RP, between 2013 and 2018, and had adverse pathological features (positive margin, and/or pT3a or higher) on final pathology. Genomic profile was available for all these men. The clinical recurrence-free survival was estimated using the Kaplan–Meier method. The external validity of the nomogram was tested using the concordance index (c-index), calibration plot, and decision curve analysis.

Results

The median follow-up of the cohort was 26.5 months. Overall, 14% of the patients received aRT. During the follow-up period, 3.4% of the patients developed metastasis. Overall 3-year metastasis-free survival was 95% (95% CI 0.92–0.98). The c-index of the nomogram was 0.84. The calibration of the model was favorable. Decision-curve analysis showed a positive net benefit for probabilities ranging between 0.01 and 0.09, with the highest difference at threshold probability around 0.05. At that threshold, the net benefit is 0.06 for the model and 0 for treating all the patients.

Conclusion

Our report is the first to confirm the validity of this genomic-based risk-stratification tool in identifying men who might benefit from aRT after RP. As such, it can be a useful instrument to be incorporated in shared decision making on whether administration of aRT will lead to a clinically meaningful benefit. Such a model can also be useful for patients’ classification in future clinical trials.

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Authors and Affiliations

  1. Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA

    David I. Lee

  2. Department of Surgery, King Hussein Cancer Center, Amman, Jordan

    Mohammed Shahait

  3. Vattikuti Urology Institute (VUI), Henry Ford Hospital, Detroit, USA

    Mohammed Shahait

  4. Department of Pathology, Perelman School of Medicine University of Pennsylvania, Philadelphia, USA

    Deepansh Dalela & Jacob Keeley

  5. Department of Radiation Oncology, Perelman School of Medicine University of Pennsylvania, Philadelphia, USA

    Priti Lal

  6. Wayne State University, Detroit, USA

    Neha Vapiwala

  7. VUI Center for Outcomes Research Analytics and Evaluation, Senior staff, Vattikuti Urology Institute (VUI), Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI, 48202-2689, USA

    Firas Abdollah

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  1. David I. Lee
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  2. Mohammed Shahait
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  3. Deepansh Dalela
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  4. Jacob Keeley
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Contributions

DIL: concept, manuscript writing. MS: concept, data collection, manuscript writing. DD: manuscript editing. JK: data analysis. PL: manuscript editing. NV: manuscript editing. FA: result interpretation, manuscript writing and editing.

Corresponding author

Correspondence to Firas Abdollah.

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Conflict of interest

Firas Abdollah is a consultant for GenomeDx Biosciences.

Ethical approval

Approved by the IRB of the University of Pennsylvania.

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Lee, D.I., Shahait, M., Dalela, D. et al. External validation of genomic classifier-based risk-stratification tool to identify candidates for adjuvant radiation therapy in patients with prostate cancer. World J Urol 39, 3217–3222 (2021). https://doi.org/10.1007/s00345-020-03540-1

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  • DOI: https://doi.org/10.1007/s00345-020-03540-1

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