Caring for Patients With Cancer in the Face of Self-Vulnerability During the COVID-19 Pandemic—Reply
Authors: Coral Olazagasti, Nagashree Seetharamu
Journal: JAMA Oncology (2020)

All that glitters is not gold; Often have you heard that told: Many a man his life hath sold… Your answer had not been inscroll'd: Fare you well; your suit is cold.Shakespeare, The Merchant of Venice, act 2, scene 7In Reply The famous allegory within this play involves suitors of Portia choosing among gold, silver, or iron caskets for the right to her hand in marriage.Ultimately, a poor Venetian correctly chooses the iron casket and they return to Venice to marry.We thank Briganti et al for their kind comments regarding our Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) trial 1 and respond to their arguments as summarized into thematic questions: (1) The definition of oligometastasis and how we chose our end points; and(2) whether all oligorecurrent castration-sensitive prostate cancers (oligoCSPCs) should be treated with systemic therapy and metastasis-directed therapy (MDT).The oligometastatic state 2 is defined by cases that may be amenable to a curative therapeutic strategy, namely through MDT.We could not have cleanly answered, in our ORIOLE trial, this very critical question of whether stereotactic ablative radiation (SABR) local therapy alone could alter the natural history of metastatic disease with systemic therapy onboard.OligoCSPC may be in fact the only space in oncology where we could answer this question.Our primary and secondary end points were chosen with a phase 2 signal-finding goal 3 balanced against the potential harm of forestalling standard-ofcare systemic therapy. 4Therefore, our primary end point was by design short and complemented by our secondary and exploratory end points, whereby which we demonstrated that the oligometastatic state may exist in CSPC, as shown by highly significant improvements not only in progression-free survival but, importantly, the development of new metastases by MDT alone. 1 With the short observation arm as a comparator, we were also able to definitively show in humans that SABR itself generates an adaptive systemic immune response. 1 In the era of precision medicine, we do not strive to treat all patients the same, but to neither overtreat nor undertreat any patients.We do not accept the assumption that all oli-goCSPCs have the same biology and should be treated identically.Preliminary data suggest that oligoCSPC is a heterogenous collection of risk groups. 4 There are certainly patients with oligoCSPC with more aggressive biology that will need systemic therapy and MDT, but per retrospective data (eg, ≥23% long-term disease control following MDT alone from Suardi and colleagues 5 ) and the prospective circulating tumor DNA stratified cohort from ORIOLE, there are sizeable fractions of men who benefit meaningfully from complete consolidation with just MDT alone.Thus, it is important to perform research that seeks to identify and inform about all these different oligoCSPC risk groups. 6 In conclusion, the meaning of the "all that glitters is not gold" allegory is that constructs of substance are not a matter of superficial golden appearance, but are in fact made of far more mundane, resolute metal.Similarly, we view the