Putting patients first to redefine prostate cancer classifications Free

The debate over removing the cancer designation for low-grade prostate cancer has taken center-stage recently. Proponents of a name change for grade group 1 (GG1) prostate cancer cite 1) extremely low rates of progression, metastasis, and death; 2) patient anxiety related to having a cancer diagnosis; and 3) the harms of overdiagnosis and overtreatment as reasons to remove the cancer label from GG1 prostate cancer (1). Opponents of this name change point to the fact that 1) although less common, patients with GG1 cancers can demonstrate extraprostatic extension, metastases, and recurrence following treatment; 2) GG1 cancers meet the histologic definition of a cancer (ie, loss of the basement membrane); and 3) the name change may lead to adverse oncologic outcomes if any of the 25%-50% of patients with prostate cancer reclassification are lost to follow-up because of removal of the cancer label (2,3).

In this important study, Berlin and colleagues (4) use a quantitative approach rooted in discrete choice experiments to assess patient perspective in 3 distinct populations: healthy individuals, canonical partners, and individuals with GG1 prostate cancer. Across all 3 cohorts, study participants favored noncancer labels for GG1 prostate cancer (P < .01), and a presentation of a noncancer label compared with a cancer label was associated with a higher preference for active surveillance (4). This confirms our intuition that a cancer label induces anxiety and fear of cancer progression that may be impervious to even the best clinician’s counseling. The main limitation of this approach is that the results are confined to patient perspectives of simulated scenarios, and discrete choice experiments are largely testing preferences between specific choices without accounting for the many other factors that influence preference and choice, including health literacy, cultural values and norms, and a wide range of social factors. This methodologic approach likely simplifies a complex decision process that involves a wide range of inputs that span beyond the discrete choices presented in this study. For this reason, other approaches including larger sample surveys and qualitative research methods that include a diverse patient population to assess knowledge, attitudes, and preferences for a name change could provide additional insight that complements the results of this study.

Clinicians and researchers who are in favor of a name change have recommended re-assigning GG1 prostate cancer the designation of prostatic acinar neoplasm of low malignant potential or prostatic acinar neoplasm of uncertain malignant potential (1,4). These patients would be recommended to undergo follow-up similar to current active surveillance protocols with routine prostate-specific antigen testing and interval prostate biopsies (1). The recommendation for removing the cancer label for GG1 is susceptible to the many challenges in the management of prostate cancer. Foremost is the tremendous heterogeneity in cancer phenotypes that patients present with at diagnosis, following treatment, and in survivorship. This wide range of cancer phenotypes—coupled with a high incidence and prevalence—increases the risk of overdetecting and overtreating low-risk prostate cancers. Of the 290 000 individuals (5) estimated to be diagnosed with prostate cancer in 2023, roughly 25%-40% (6,7) of them will be diagnosed with a low-risk prostate cancer. The natural history of these cancers is overwhelmingly indolent, with less than 1%-3% of these patients developing metastatic prostate cancer (8,9). Perhaps more importantly, few individuals with low-risk prostate cancer have died from prostate cancer (<1%) with close monitoring with routine prostate-specific antigen testing and prostate biopsy with up to 15 years of follow-up (8,9).

Historically, approximately 30% of individuals with GG1 prostate cancer experience a cancer grade reclassification at biopsy within 1 year following their initial diagnosis (10). These upgrading events are termed reclassification because they are more likely a result of differential prostate sampling at surveillance biopsy rather than cancer progression. Prostate cancer is the only solid organ cancer that employs a systematic, templated biopsy that aims to provide a representative sample of the whole gland tissue rather than utilizing biopsies directed at suspicious radiographic lesions. The recent addition of prostate magnetic resonance imaging (MRI) and targeted biopsies has improved the detection of clinically significant prostate cancers and the quality of prostate biopsies to detect cancer (11,12). Studies have shown that MRI still misses approximately 20% of tumors detected on systematic biopsy, which is a limitation of relying on target-only biopsies for diagnosing prostate cancer (11). Studies of prostate MRI in active surveillance populations have not demonstrated a strong link between MRI use and cancer reclassification (13,14). However, MRI may improve patient selection for observation if used at initial diagnostic biopsy (14). The diagnostic challenges of prostate cancer—a largely multifocal cancer—combined with the aforementioned heterogeneity of prostate cancer creates an important consideration in the debate. It is important to note that cancer grade reclassification is the main driver for definitive treatment use in the 50% or more of individuals with low-risk prostate cancer undergoing active surveillance with long-term follow-up (8,9). It is unclear from the work of Berlin and colleagues (4) how patients would feel about name changes with these risk for reclassification and/or treatment over 10-15 years.

A 2023 meeting of prostate cancer experts in San Francisco, California, led to the creation of a working group that aims to create a systematic consensus process for renaming GG1 prostate cancer. However, that debate and discussion have not always been centered around a broad representation of patient voices and perspectives. Previous studies have demonstrated that patient input in prostate and bladder cancer can provide important and sometimes unique insight into patients’ priorities around their research and clinical needs (15-17). We commend the authors for taking an important first step toward understanding the patient perspective of the impact of removing the cancer label from GG1 prostate cancer. However, more needs to be done to incorporate the patient voice in the discussion of a major change to the terms we use to describe prostate cancer. Involving patients in the prioritization, design, and implementation of important clinical and research priorities in bladder and endometrial cancer—through partnerships with the Bladder Cancer Advocacy Network and Endometrial Cancer Action Network for African-Americans, respectively—are driving important research initiatives to improve patient outcomes and quality of life through patient-engaged research and action through large multisite phase IV studies (16,18,19).

Incorporating the patient voice as a research partner creates value and drives meaningful study design and implementation. In prostate cancer, important clinical ideas have demonstrated implementation difficulties (ie, accrual challenges) in several clinical trials addressing important topics. These difficulties may have been diminished had patients been meaningfully engaged in discussions around the prioritization of these topics and in the design of these studies. As a methodology, patient-centered outcomes research provides a framework for engagement (ie, partnership; transparency, honesty, and trust; co-operative learning; and reciprocal relationships) to center our research efforts around our patients by making them research partners and collaborators. In bladder cancer, engagement of patient and bladder cancer advocates highlighted that patients would not be willing to enroll in a randomized study of cystectomy vs bladder-sparing therapies for recurrent, nonmuscle invasive bladder cancer (16). This information led to the pragmatic study design of the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer study. This decision to pursue a nonrandomized study design to answer an important clinical question to patients and clinicians was later validated by the results of a feasibility trial in the United Kingdom demonstrating that patients would not participate in a randomized trial (20).

There are important lessons to learn from the challenges we have experienced with clinical trial accrual in prostate cancer and from the recent successes of patient engagement in bladder cancer. Given the gravity of this discussion around a name change in prostate cancer, research collaboration and partnership with our prostate cancer patients and advocates are paramount to ensuring that the questions we ask, the approaches we take, and the interpretation of our results represent the experiences, perspectives, and preferences of our patients and the individuals (ie, their partners, primary care providers) who support them. Ultimately, the decision to remove the cancer label may be the right one if it serves the needs of our patients in managing these low-grade and low-risk cancers. As the debate goes on, it is with strong partnership with our patients and prostate cancer advocacy communities that we will find the correct path forward on how we address the cancer designation of low-grade prostate cancers.

Data availability

No new data were generated or analyzed for this editorial.

Author contributions

Yaw A Nyame, MD, MS, MBA (Conceptualization; Writing—original draft; Writing—review & editing), John L Gore, MD, MS (Writing—review & editing), and Daniel W Lin, MD (Writing—review & editing).

Conflict of interest

The authors report no relevant conflicts of interest with regards to this editorial. YAN is a consultant for Ortho-Clinical Diagnostic.

Acknowledgement

YAN is supported by the US Department of Defense, Office of the Congressionally Directed Medical Research Programs (W81XWH2110531). YAN, JLG, and DWL are supported by the NCI (P50CA97186).

The funders did not play a role in writing of the editorial or the decision to submit the manuscript for publication.

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