Researchers at the Johns Hopkins Kimmel Cancer Centre and its Bloomberg~Kimmel Institute for Cancer Immunotherapy have released updated consensus guidelines and an associated reproducibility study to standardise how pathologists assess tumour response to neoadjuvant therapy (administered prior to surgery) across a dozen solid tumour types.

The work was funded in part by the National Institutes of Health and The Mark Foundation, and it was completed in collaboration with the Society for Immunotherapy of Cancer (SITC) and the International Neoadjuvant Melanoma Consortium (INMC).

The recommendations, published Nov. 4 in Annals of Oncology, provide the first unified, pan-tumour framework for evaluating residual viable tumour (RVT, the amount of cancer cells remaining), necrosis (cancer cell death) and regression (a constellation of histologic findings that includes inflammation and features of wound healing) after presurgical treatment.

They refine and expand earlier immune-related criteria first proposed in lung cancer in 2018, and in a pan-tumour fashion in 2020, which are now updated based on five years of real-world use, questions from the field and new reproducibility data.

A related reproducibility study, published Feb. 2 in Annals of Oncology, found that the tumour guidelines can be applied across many different tumour types and achieve consistent results when used by different pathologists around the world.

“Neoadjuvant therapy is rapidly expanding across cancer types, and pathologic response is emerging as a predictor of long-term survival and an important clinical trial endpoint,” says lead author Julie Stein Deutsch, M.D., assistant professor of dermatology, pathology and oncology.

“However, scoring systems have varied widely by tumour type, making it difficult to compare across studies or apply results reliably in practice. This unified approach establishes a common language that will benefit clinical care, research and future regulatory use.”

The updated framework was prompted by growing evidence that tissue changes seen under a microscope that indicate a cancer is shrinking or responding to treatment — particularly after immunotherapy — appear remarkably consistent across cancers.

The research team previously reviewed about 500 specimens treated with anti-PD-1 immunotherapy drugs alone or in combination with other agents (such as chemotherapy or targeted therapy) and observed similar patterns of response regardless of tumour origin.

John Hopkins Kimmel Cancer Centre investigators worked with SITC and INMC to create a single, harmonised standard, recognising that parallel systems risked confusion and limited comparability.

“Most pathologists around the world are generalists, not tumour-type specialists,” says senior author Janis Taube, M.D., director of dermatopathology and co-director of the Bloomberg~Kimmel Institute tumour microenvironment laboratory.

“Switching between multiple scoring systems is inefficient and can lead to inconsistent reporting. Our findings support a pan-tumour system — and importantly, no existing tumour-specific system outperforms this unified approach in predicting patient outcomes.”

A major advance with the new guidelines is their demonstrated reproducibility, the researchers say.

In a multi-institutional, international study involving 14 pathologists, RVT scoring using the updated criteria proved highly reproducible after a short, standardised training session.

Using the standardised criteria, pathologists demonstrated high concordance in scoring RVT, regression and necrosis, regardless of tumour type, anatomic location or whether the specimen was a surgical resection or biopsy.

The findings were presented at the American Society of Clinical Oncology annual meeting in 2024.

These findings reinforce the rationale for a unified, pan-tumour approach to pathologic response assessment comparable to Response Evaluation Criteria in Solid Tumours (RECIST), the standard method doctors use to measure how tumours change in size on imaging scans, and provide a validated foundation for standardised data collection as neoadjuvant (therapy given before surgery) and perioperative (therapy given before and after surgery) approaches continue to expand across cancer types, the researchers say.

“Reproducibility is essential,” says Deutsch.

“Different pathologists must arrive at similar scores if these metrics are going to guide patient care and clinical trials. Our training materials make that possible, and we are partnering with SITC to disseminate these resources.” The researchers say next steps include refining clinically meaningful RVT thresholds for specific tumour types as additional survival data become available.

Source: Johns Hopkins Medicine