A peer-level look at how oncologists monitor emerging resistance, repeat molecular testing after progression, interpret actionability, and decide what to do when a new molecular finding does not automatically create a new treatment option.
Audience: Oncologists
Countries: 6
Completion Rate: 72.2%
SGID: 8975843
-Hero findings
– Quick Read — Key Findings
Targeted therapy can produce deep or durable responses when a tumor remains dependent on the molecular pathway being targeted. Progression changes the problem. The oncologist must decide whether the original target has evolved, whether a bypass pathway has emerged, whether disease biology has changed more broadly, and whether a test result can be translated into a treatment that is actually available.
The National Cancer Institute notes that cancers can become resistant when the target itself changes or when tumor cells find alternative ways to grow, and that biomarker profiles can shift over time, which is one reason repeat testing may be considered when disease returns or progresses. The MDForLives survey focuses on that transition point: how often resistance is encountered, when oncologists monitor for it, how repeat molecular testing is used, what makes a result actionable, and why post-progression treatment can stay difficult even when the biology is better defined.
45.1% say they encounter primary or acquired resistance frequently, while another 23.9% encounter it very frequently.
For many oncologists, resistance is not an exceptional end-stage event but part of the expected journey once a patient stays on targeted therapy long enough for tumor evolution, clonal selection, or bypass signaling to matter. That frequency changes the value of preparedness: a practice that expects resistance can set up the testing pathway, tissue-or-blood strategy, multidisciplinary review, and next-line evidence questions before progression forces all of them into a single visit.
63.8% say molecular findings or the resistance mechanism influence the next treatment strategy; 58.0% also prioritize evidence for available options and 53.6% the patient’s clinical status and disease trajectory.
The hierarchy matters: molecular information is the most selected input, but it sits beside evidence and disease trajectory, and a new alteration only becomes useful when the oncologist can judge whether it truly drives resistance, whether a matched strategy has meaningful evidence, and whether the patient can benefit now. That is why post-progression precision oncology remains a synthesis problem, moving from progression to mechanism, actionability, evidence, and patient context before treatment selection, not straight from mutation to drug.
34.8% routinely use molecular or clinical monitoring in appropriate patients before clear progression, while repeat testing is most often used selectively according to cancer type and treatment history.
The survey does not show a single universal surveillance model; oncologists use molecular monitoring and retesting where the expected information gain justifies the test and where cancer type, prior therapy, and likely resistance mechanisms make the result interpretable. Disease-specific guidance shows why: in advanced NSCLC with driver alterations, current ASCO guidance advises assessing for new mutations after progression because new targetable mechanisms can emerge, a principle that does not generalize identically across cancers but shows retesting is most valuable when there is a plausible treatment consequence.
44.9% use repeat testing primarily to identify an actionable resistance mutation or biomarker, and the same 44.9% use it to guide selection or sequencing of subsequent therapy.
The tie is revealing: repeat testing is not treated only as a diagnostic exercise, but as a request for a result that explains the resistance and changes the treatment sequence. NCI similarly notes that biomarker testing can identify treatment-linked changes yet also return findings that do not support a treatment decision, a distinction that matters more after progression, when the pressure to translate information into action is greatest.
68.1% identify limited effective treatment options after progression as a major barrier, ahead of difficulty identifying actionable resistance mechanisms at 47.8%.
This is the central tension: better molecular characterization does not guarantee a better therapeutic choice, because a mechanism can be identified and still have no approved, accessible, evidence-supported, or tolerable next option. The same tension helps explain why 53.6% say molecular information changes the strategy only sometimes, in selected patients, since the clinical utility of testing is constrained by the therapy landscape around the result.
45.6% expect more effective resistance-targeted therapies and combinations to have the greatest impact over the next 3–5 years; 33.8% choose earlier resistance detection through ctDNA and molecular monitoring.
The ordering is important: earlier detection is valuable, but respondents put greater weight on having better therapies to act on the information, mirroring the barrier data where limited effective options outrank testing access or turnaround. The open-ended responses reinforce it, returning repeatedly to earlier or more standardized molecular testing, better identification of resistance mechanisms, effective second-line or resistance-specific therapies, and closer multidisciplinary correlation between results and treatment.
Across the findings, oncologists appear comfortable with the principle that resistance should be investigated. Molecular findings influence the next strategy, repeat testing is common in selected settings, and resistance-guided therapy leads once a new actionable pathway is identified.
But the strongest barrier sits downstream: limited effective treatment options after progression, which reframes every earlier step, since monitoring, ctDNA, tissue re-biopsy, NGS, and molecular tumor-board review are most useful when they connect to a decision that is evidence-supported, available, and appropriate for the patient’s trajectory. So the survey points to a practical next phase for targeted therapy resistance: detect the mechanism earlier where it matters, interpret it more consistently, and expand the treatment options that turn molecular information into a meaningful change in care
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Direct answers to common clinical questions about acquired resistance, repeat molecular testing, ctDNA, actionability, and treatment selection after progression.
Direct answers to the questions healthcare professionals are most likely to ask about these findings.
