Prof Declan Murphy discusses PROTEUS pathologic response findings in prostate cancer

In this video, Declan Murphy, MB, BCH, BaO, FRACS, FRCS, Urol, discusses the pathologic outcomes from the phase 3 PROTEUS trial (NCT03767244) and what the findings may mean for treatment of high-risk localized or locally advanced prostate cancer. Murphy is a urologist and the director of GU oncology at the Peter McCallum Cancer Center in Melbourne, Australia.

Murphy explains that the PROTEUS trial met its co-primary pathologic end point, demonstrating a 9-fold increase in pathologic complete response or minimal residual disease (pCR/MRD) with neoadjuvant apalutamide (Erleada) plus androgen deprivation therapy (ADT) compared with ADT alone.¹ However, he emphasizes that the headline result should be interpreted in the context of the relatively low absolute rates, with pCR/MRD occurring in approximately 9% of patients in the intensified-treatment arm vs 1% in the control arm (OR, 10.17; 95% CI, 5.27 to 19.64; P < .0001). Despite the substantial relative improvement, most patients continued to have significant residual cancer in the prostate, underscoring the importance of local therapy.

“Systemic therapy on its own is clearly not good enough for the management of this type of cancer,” Murphy says, noting that surgery and radiation remain critical components of treatment.

Murphy also highlights the trial’s exploratory residual cancer burden (RCB) analysis as a potentially important avenue for future research. A RCB of of 0.25 cm³ or smaller was observed in 30.6% of patients receiving apalutamide plus ADT vs 11.7% of those receiving ADT alone (OR, 3.36; 95% CI, 2.67 to 4.23; P < .0001). Murphy suggests that these findings could eventually support response-adapted treatment strategies, in which patients demonstrating a profound response after 6 months of intensified neoadjuvant therapy could be evaluated for whether they need the full additional 6 months of adjuvant treatment. Although this approach remains a hypothesis, he sees the ability to stratify patients according to their pathologic response as an important direction for future clinical trials.

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