How do case reports and retrospective series influence clinical adoption of PRRT compared with randomized evidence?
Executive summary
Case reports and retrospective series often act as the spark that draws clinical attention to interventions such as peptide receptor radionuclide therapy (PRRT), providing early signals of feasibility, safety and real‑world outcomes that randomized controlled trials (RCTs) later test more rigorously [1] [2]. However, the hierarchy of evidence and the strengths of randomization mean that widespread, guideline‑level adoption typically requires confirmatory RCTs or large, well‑designed observational cohorts to resolve bias and confounding [3] [4].
1. Early signals: how case reports and series create clinical momentum
Case reports and small retrospective series are uniquely positioned to detect novel effects or adverse events and to document feasibility in complex therapies; by describing new or unusual treatments they alert clinicians and generate hypotheses for further study [1] [5]. These descriptive reports are relatively easy and quick to produce and therefore often drive early off‑label use or compassionate‑use programs by showing that patients can be treated and sometimes benefit in routine settings [5] [6].
2. Real‑world credibility: retrospective series and external validity
Retrospective cohorts and registry analyses can include more diverse, comorbid and older patients than many RCTs, thereby demonstrating effectiveness in real‑world practice and longer follow‑up for safety signals—information clinicians value when deciding whether to adopt a specialized therapy [7] [8]. Advances in analytic methods such as propensity scoring have strengthened observational inferences, enabling these studies to estimate treatment effects where RCTs are lacking or impractical [9].
3. Limits of descriptive evidence: bias, confounding and the risk of premature adoption
Despite their practical value, case reports and retrospective series are vulnerable to selection bias, confounding by indication and incomplete data capture, which can exaggerate benefits or underreport harms—weaknesses that limit causal inference and can mislead clinical practice if relied upon alone [1] [10]. The traditional evidence hierarchy places RCTs above case series for a reason: randomization minimizes confounding and strengthens claims of causality, which is essential before declaring a therapy superior or standard of care [3] [4].
4. Complementary roles: when observational data and RCTs should coexist
High‑quality RCTs and well‑designed observational studies serve complementary purposes: RCTs answer the question "can this work under ideal conditions?", while observational research answers "does this work in routine practice, and for whom?"—a balance particularly important for complex treatments like PRRT where patient selection, dosing, and long‑term toxicity vary across centers [9] [8]. Systematic adoption pathways often begin with case reports → retrospective cohorts → prospective studies/RCTs, with each step refining indications and safety monitoring [5] [2].
5. Practical and ethical reasons RCTs may lag and how that affects adoption
Practical barriers—rarity of disease subtypes, ethical concerns about withholding potentially effective therapy, and the logistical cost of trials—mean RCTs are sometimes delayed or infeasible, giving retrospective evidence outsized influence on practice in the interim [5] [11]. In such situations clinicians and regulators must weigh imperfect evidence from series and registries against patient need and biological plausibility, recognizing that observational signals require cautious interpretation [10] [6].
6. A cautious prescription: how clinicians should integrate evidence when RCTs are absent
The prudent path is to treat case reports and retrospective series as hypothesis‑generating and operationally informative but not definitive: use them to identify candidate patients, inform consent about uncertain benefit, and design prospective studies or registries that can confirm effectiveness and safety; reserve broad, guideline‑level endorsement for settings where randomized or robust comparative data exist or where observational datasets reproduce consistent signals across diverse populations [1] [8].
Note: none of the provided sources address PRRT specifically; the analysis therefore applies general principles about evidence synthesis and the interplay between case reports, retrospective series and randomized trials to therapies like PRRT rather than asserting PRRT‑specific trial outcomes.