Two international genitourinary pathology societies have published a white paper calling for improvements in the detection and diagnosis of indolent prostate cancers (PCs).
According to the new document, limitations in the ability to differentiate noncancerous prostate lesions from more aggressive and potentially life-threatening tumors are resulting in too many patients experiencing adverse outcomes, mainly from complications of unnecessary treatment from radiation therapy and radical prostatectomy, mainly incontinence and erectile dysfunction.
To address the issue, the Genitourinary Pathology Society (GUPS) and the International Society of Urological Pathology (ISUP) are calling for a multidisciplinary team approach with urologists, radiologists, radiation oncologists, and pathologists determining how best to manage cases of indolent PC. The document appeared last month in European Urology.
“Reliable identification of indolent prostate cancer at needle biopsies is not possible,” the societies stated. “This is because sampling errors, disease progression, or the different molecular makeup may contribute to such discrepancies.”
The societies define indolent PC as “low-volume, well-differentiated acinar neoplasm with invasive histologic features that do not spread outside the prostate, become symptomatic, or shorten a patient’s life if left untreated.”
Despite the overlap between clinically insignificant PC and indolent tumors, they “do not necessarily mean the same entity,” the paper said.
Gladell Paner, MD, director of Genitourinary Pathology at the University of Chicago, Chicago, and a co-author of the new document, said the new thinking represents a “major shift, with expert genitourinary pathologists now accepting that there is indeed a ‘noncancerous-behaving entity’ within our current diagnosis of prostate cancer.”
However, Paner added, “We are not yet capable of isolating these purely nonlethal tumors based on current criteria and technology.”
Glen Kristiansen, MD, past president of ISUP and chairman of the Institute of Pathology at University Hospital Bonn in Bonn, Germany, said renaming Grade Group 1 tumors as noncancerous lesions is just one approach.
“We can do something about this problem from the patient care perspective, but we cannot do it alone as pathologists,” Kristiansen said. “We need a multidisciplinary approach at this point to define indolent cancer.”
Most pathologists say Grade Group 1 looks like cancer, but many urologists say the lesions do not act like a malignancy because they tend not to spread or kill. The authors of the white paper argued that uropathologists have agreed to collaborate with urologists, radiologists, and radiation oncologists to reach an interdisciplinary consensus to write new guidelines and patient-centered pathology reports.
A similar multidisciplinary process occurred in redefining certain thyroid growths as noncancers, as reported in JAMA in 2016.
‘Smoldering’ no Longer
Redefining Grade Group 1 prostate tumors as noncancers has been debated for years, but pathologists, in particular, have resisted the idea.
Mathew Cooperberg, MD, MPH, the Helen Diller Family Chair in Urology at the University of California, San Francisco, said the white paper could lead urologists and other prostate experts to collaborate with uropathologists to develop new guidelines to redefine Grade Group 1 tumors and spare these patients from the emotional distress and financial toxicities that often accompany a diagnosis of cancer.
The document “shows that this question, after a lot of years of smoldering, is getting the appropriate attention that it deserves at the highest levels. Really clear engagement from the pathology community is essential,” Cooperberg said.
Rajal B. Shah, MD, immediate past president of GUPS and a senior uropathologist at the UT Southwestern Medical Center in Dallas, and the lead author on the white paper, said a multidisciplinary approach to the problem includes integrating clinical, pathological, genomic, and radiological information unique to each patient to better understand the disease.
Shah said the goal of the effort is to educate stakeholders involved in PC care, including urologists, radiologists, radiation oncologists, and pathologists, that not all Grade Group 1 lesions can effectively be identified as indolent with 100% accuracy.
Shah said the field needs more collaboration, research support, and resources to better identify which Grade Group 1 or Gleason score 6 cancers diagnosed in prostate needle biopsies are truly indolent and can be safely watched by patients enrolling in active surveillance vs men who should be treated.
The document cites a controversial 2024 Danish study in European Urology Oncology that reported 14% of men found to have indolent lesions died from PC within 15 years of diagnosis. The authors said defects in the study, such as a lack of central pathology review, likely resulted in the mortality rate attributable to true Grade Group 1 PCs being much higher than would be anticipated.
Approximately 20%-30% of Grade Group 1 tumors on initial biopsy are upgraded to a higher grade following a radical prostatectomy.
Ming Zhou, MD, PhD, past president of GUPS and vice chair of Oncological Pathology at Mount Sinai Health System in New York City, said that while he signed the white paper, he felt it did not go far enough. “I do not think you will ever succeed in persuading pathologists to think GG1 [Grade Group 1] is not cancer-based on pathology and genetics. But for patient management, we should consider labeling it as noncancer,” he said.
No relevant financial conflicts were reported.
Howard Wolinsky is a Chicago-based medical writer. He has been working on a study funded by the US Centers for Disease Control and Prevention with Cooperberg and Paner which, in part, will gather minority patients’ views on the renaming of Grade Group 1 as a noncancer.