In addition to the role prior to diagnosis and following diagnosis before treatment that was discussed in previous sessions, genomic testing may assist with important treatment decisions following radical prostatectomy including whether to offer early radiotherapy or simply observation and, among those with biochemical recurrence, whether to intensify therapy with androgen deprivation in addition to radiotherapy.
In this setting, both Decipher and Prolaris may provide actionable information. Decipher was designed around the prognostication of metastasis, an endpoint which has recently been shown to be much more strongly associated with overall survival than other, predominately PSA-based, surrogates.
In this setting, following radical prostatectomy, the reported output of genomic testing appears similar to those derived from biopsy pathology.
Dr. Wagner highlighted data that, compared to conventionally utilized clinicopathologic features including PSA, stage, grade, and NCCN or CAPRA nomograms, Decipher has a higher AUC for the prediction of development of metastasis. Depending on when it is performed, this information may be useful in driving decisions whether to offer adjuvant versus salvage radiotherapy or whether to offer androgen deprivation therapy with postoperative radiotherapy.
Dr. Wagner briefly cited more than a dozen studies supporting the utility of genomic testing in each of these clinical scenarios.
Assessing the first of these scenarios, immediately following radical prostatectomy, Dr. Wagner described that the use of Decipher can result in intensified post-operative care, either with closer follow-up or adjuvant radiotherapy. Further, there are data to support that Decipher may be predictive of the benefit of early postoperative radiotherapy. In patients with low Decipher scores, the cumulative incidence of metastasis was similar for patients who underwent either early adjuvant radiotherapy or salvage radiotherapy. In contrast, for those with high Decipher scores, the early initiation of radiotherapy was associated with a significantly lower rate of metastases.
These results were subsequently validated in a prospective study in which Decipher test results were used to inform treatment recommendations: in patients with low or intermediate Decipher scores, rates of metastasis were similarly low whether patients followed recommendations (observation) or underwent adjuvant radiotherapy. In contrast, those with high Decipher scores who followed recommendations (radiotherapy with or without ADT) had significantly lower rates of metastasis than those who opted for observation.
Dr. Wagner then provided a number of hypothetical examples in which the addition of genomic risk stratification may change therapeutic decisions, for patients with comparable clinicopathologic characteristics.
Further, in patients who initially opted for post-operative observation and have now developed biochemical recurrence, the Decipher score may provide risk prognostication that can aid with the decision whether to use concurrent ADT with salvage radiotherapy. While the RTOG 9601 trial demonstrated the benefit of hormone therapy when added to salvage radiotherapy for patients with biochemical recurrence following radical prostatectomy. A retrospective analysis of this study demonstrated that Decipher risk category significantly modified the benefit of adding ADT: while the addition of ADT improved distant metastasis, prostate-cancer specific mortality, and overall survival for men with intermediate and high Decipher scores, rates of distant metastasis and prostate cancer specific mortality were marginally improved for patients receiving ADT who had low Decipher risk and overall survival was actually worse with ADT in this group.
Again, Dr. Wagner provided a number of hypothetical examples to support the use of genomic testing in this disease space. He further highlighted that Decipher is the only molecular assay recommended in the NCCN guidelines for radiotherapy following radical prostatectomy.
In addition to these data examining Decipher, Prolaris has also been assessed in this space. Notably, while Decipher used metastasis as the key endpoint for test derivation and validation, Prolaris is designed based on biochemical recurrence as the outcome of interest. Prolaris leverages not just the genomic information, but also clinical features as captured in the CAPRA-S score, to provide a clinically validated 10-year risk of biochemical recurrence. As with Decipher, there is a wealth of literature supporting the use of Prolaris in this space.
Further, while originally designed to predict biochemical recurrence, when combined with clinical data, Prolaris has recently been shown to be prognostic of metastasis and death following radical prostatectomy.
This ability to predict the development of metastasis and death following radical prostatectomy may allow the identification at increased risk of treatment failure who could benefit from early subsequent therapy. In addition, recent work which is not yet published from Dr. Trock suggested that Prolaris could be used in a dichotomous fashion (CCR score 2.242 as cut-off) to guide treatment decisions with those above the threshold having a high probability of treatment failure and thus having the greatest potential to benefit from further therapy.
Concluding, Dr. Wagner summarized that Prolaris provides further risk stratification within each clinicopathologically defined risk group with the ability to identify patients at high risk of biochemical recurrence, metastasis and death who may benefit from further therapy.
Presented by: Joseph Robert Wagner, MD, Chief, Urology, Hartford Hospital & Director, Robotic Surgery, Hartford Hospital
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, @WallisCJD on Twitter during the AUA2021 May Kick-off Weekend May 21-23