Author:

Francesco Perrone

Abstract

Inspired by a 2014 call to action from American oncologist Nandita Khera, Italian researchers discovered that, despite universal healthcare coverage, 26% of cancer patients reported financial difficulties before treatment, with younger patients, women, and those in southern Italy most affected. Financial distress correlated with poorer quality of life and increased mortality risk. The study led to development of PROFFIT (Patient Reported Outcome for Fighting Financial Toxicity), a 16-question tool specifically designed for the Italian healthcare context, which identifies causes of financial burden, including transportation costs, care coordination inefficiencies, and out-of-pocket expenses. Recognized by ESMO in 2024 as a validated alternative to the American COST questionnaire, PROFFIT has been adapted for use in the UK and is being validated in Turkey, demonstrating that financial toxicity remains a significant issue even in universal healthcare systems.

Introduction

In 2014, in a section of the Journal of Clinical Oncology called Art of Oncology, a young American oncologist, Nandita Khera, wrote a brief and highly provocative article calling for evaluating and reporting the financial toxicity of cancer treatments ^[1]. Until that moment, oncologists had focused primarily on the efficacy of treatments and their medical toxicities, not their economic impact.

Khera described two young patients who were offered palliative therapies that, at best, might extend their survival by a few months, at the cost not only of potential medical toxicities but also of a significant financial burden that would severely affect their families’ economic stability. Both patients asked her for advice on how to manage the cost of these treatments, and she simply admitted she was unable to respond. Ultimately, both patients made decisions influenced more by economic considerations than by their health status.

A Scientific Call to Action

Khera’s article was both a provocation and a pressing request to the scientific community: to take seriously the economic impact of cancer care and to measure it just as we have always measured and categorized medical toxicities.

The provocation hit the mark, as the scientific literature began to fill with publications on financial toxicity in cancer care. From 205 articles published and indexed by PubMed in 2014 to 5,518 by 2024 (keywords: ((financial toxicity) OR (financial hardship)) AND (cancer)).

The first articles, unsurprisingly, came from the United States, where the healthcare system structure inevitably involves significant patient contributions to cancer treatment costs. These articles demonstrated that cancer patients are at a much higher risk of bankruptcy than non-cancer individuals of similar age and gender ^[2]. Studies showed that cancer patients experiencing financial hardship have a lower quality of life than those who are economically stable ^[3]. Other studies revealed that bankruptcy is associated with a higher risk of death—an hazard ratio of 1.79—for American cancer patients ^[4].

The Italian Experience and Initial Findings

Khera’s call to action also prompted reflection in Italy, where it was believed that the existence of the National Health Service (SSN) protected patients from the effects described in the United States. In 2016, encouraged by articles indicating that tools had long existed to measure the economic effects of cancer, researchers decided to explore clinical trial databases coordinated by the National Cancer Institute of Naples over the previous two decades to identify signs of financial distress among patients.

The data came from 16 prospective clinical trials promoted by the Institute, all of which used the EORTC C30 questionnaire, which includes question 28 asking whether physical conditions and medical treatment caused financial difficulties in the past 7 days. These trials, already closed and published, included a total of 3,670 patients with lung, breast, or ovarian cancer ^[5].

The first finding was that 26% of patients reported some degree of financial difficulty before starting treatment. This percentage was higher among patients under 65 years (33%), female patients (32%), and those enrolled by oncology centers in central or southern Italy and the islands. The second significant finding was a correlation between baseline financial distress and post-treatment quality of life: patients reporting economic hardship at the start had a 35% higher risk of worsened quality of life after treatment. Moreover, 22.5% of patients worsened their response to question 28 during treatment and—unexpectedly—had a higher risk of death (hazard ratio 1.20) compared to those who did not worsen. Although less extreme than the U.S. hazard ratio of 1.79, this finding is significant, especially considering that in Italy, antineoplastic drugs are fully covered by the SSN and the study population enrolled in clinical trials could have been potentially socioeconomically advantaged.

The Need for a Dedicated Measurement Tool

Question 28 of the EORTC C30 questionnaire is simple and direct but not very explanatory. The information that one person had financial difficulties in the past week reveals nothing about the type or cause of those difficulties. A deeper investigation was needed.

Based on these premises, and thanks to funding from AIRC (Italian Association for Cancer Research), a project was launched to develop a tool for measuring financial toxicity in Italy and identifying its determinants. The methodology mirrored that used in the United States to develop the COST questionnaire ^[6], formalized by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), and based on contributions from caregivers and especially patients ^[7].

The decision to create a new tool in Italy was supported by other authors ^[8], recognizing that financial toxicity is strongly shaped by the healthcare system structure. The differences between the U.S. and Italy were significant, and a mere translation of the American tool would likely have missed key aspects ^[9]. Subsequent research confirmed this relevant point. COST, with its 11 questions, mainly explores psychological reactions to financial toxicity—as paying for cancer care is normal for American patients. In contrast, the Italian tool includes many items about the causes of financial toxicity, reflecting how Italian patients react by questioning the reasons behind their financial burden.

PROFFIT: Development, Validation, and Impact

The Italian tool, named PROFFIT (Patient Reported Outcome for Fighting Financial Toxicity), consists of 16 questions. From the outset, the goal was not only to describe the extent of financial toxicity but also to identify its causes and determinants to inform potential healthcare policy changes. Seven items form the PROFFIT-score, ranging from 0 to 100, estimating the respondent’s financial difficulties. The remaining nine items are considered individually and represent potential determinants of financial toxicity, grouped into three conceptual areas: (i) transportation and distance from care centers, (ii) efficiency of SSN care coordination, and (iii) out-of-pocket expenses not adequately covered by the SSN.

A series of studies were conducted to develop and validate PROFFIT for reliability ^{[7] [10]}. It was later validated in an independent cohort to assess its correlation with responses to question 28 and with patients’ reported quality of life ^[11]. Recent analyses confirmed the medium-term stability of these correlations (submitted).

In 2023, PROFFIT was translated and validated for use in the UK, based on structural similarities between the Italian SSN and the British NHS ^[12]. A Turkish version is currently under validation ^[13].

In 2024, PROFFIT was recognized in an ESMO Consensus Statement as the only validated alternative to COST for assessing financial toxicity in cancer patients ^[14]. It is now used by multiple research groups in studies focused on financial toxicity or integrated into trials comparing therapeutic strategies ^{[15] [19]}.

Conclusions

The economic impact of cancer, once ignored, is now a central topic in scientific debate. In Italy, research has shown that, despite the presence of the National Health Service, financial toxicity is a real phenomenon, perhaps negatively impacting and worsening patients' quality of life and prognosis. The development of specific measurement tools such as the PROFFIT questionnaire marks a significant step forward. Beyond quantifying the problem, PROFFIT identifies its structural causes, thus providing a solid basis for implementing targeted healthcare policies and making oncology increasingly attentive not only to clinical aspects but also to the economic and social well-being of patients. Collaboration between research centers and the use of these tools represent the path to ensuring more equitable and comprehensive cancer care.

References

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[15] NCT05947149. Health Related Quality of Life (HRQoL) in Patients With Solid Tumors Treated With Hadrontherapy (HadroQoL). 2023.

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[18] NCT06887244. Evaluation of the Effectiveness of Nurse Tele-consultation on the Quality of Elective Colonoscopy, Procedure-related Anxiety, and Financial Toxicity. 2025.

[19] NCT06955910. Assessing Financial Toxicity Using the PROFFIT Questionnaire in Patients Treated With Mini-invasive Approach for Urological Malignancies. UROFIT Study. 2025.

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[21] Key Players: Francesco Perrone, Silvia Riva