Dr. Eric Kauffman received a 2021 Young Investigator Award for his project “Biology of spontaneously regressing renal cell carcinoma primary tumors.” Kauffman is based at the Roswell Park Comprehensive Cancer Center in Buffalo, New York.
We spoke with Kauffman about his work and what it could mean for people with kidney cancer.
How frequent is frequent when you say spontaneous regression in small renal masses (SRMs) is ‘a frequent phenomenon’?
We checked for occurrence of spontaneous primary tumor regression among over 100 consecutive patients diagnosed with kidney cancer on biopsy who underwent active surveillance management, and we observed the spontaneous regression event to occur in around 1 in every 5 patients. In some cases the regression magnitude was mild, in some cases it was moderate, and in some cases it was extensive, including occasional potentially complete regression. The typical magnitude of regression was around a 70% reduction in volume. In each case, we confirmed the regression magnitude with software-assisted volumetrics and independent radiologist reviews, in order to ensure the size reduction was not due to technical factors such as imprecise original radiologic measurements. Intriguingly, the spontaneous regression event is much more frequent among less common subtypes of renal cell carcinoma collectively known as non-clear cell subtypes, where we observed regression in 1 in every 2-4 patients, depending on the specific subtype. Furthermore, the regression magnitude was significantly higher in these non-clear cell subtypes. On the other hand, spontaneous primary tumor regression of the most common kidney cancer subtype, clear cell, was pretty uncommon, at around 1 in 10 patients, with typically only mild regression of around 30-50%.
The reason we discovered frequent spontaneous regression is due in part to our unique clinical practice at Roswell Park Comprehensive Cancer Center, in which the vast majority of all SRM patients (>95% of SRM patients in my own practice) are managed with an initial period of active surveillance rather than immediate treatment. We have reported on the safety and feasibility of this “conservative” approach, and are excited to see consensus guideline groups broadening their recommendations for active surveillance in recent years.
Are these SRMs typically benign or malignant?
Spontaneous cancer regression is defined as the reduction in cancer size in the absence of treatment. All patients in this study had malignant tumors based on biopsy. Although the vast majority of these cases did not undergo surgical resection and hence were not confirmed to be malignant pathologically, our prior studies have shown 100% histological concordance with surgical resection among patients with a malignant preoperative biopsy.
Note, while most of these cases were SRMs, we did not restrict our study to SRMs (that is, tumors < 4 cm in longest diameter), and a few of the regression events were in tumors larger than 4 cm. We included all active surveillance patients with a biopsy showing kidney cancer, regardless of initial size.
Do we know why spontaneous regression happens?
Simply put, we don’t know. The event is not well studied on a molecular or cellular level. Proposed theories include possible biopsy-induced infarct within the tumor, however we have observed occasional regression prior to any biopsy, suggesting another mechanism. An immune mechanism is intuitive, especially given the increasingly apparent role of immune regulation in kidney cancer progression, as exemplified by the fact that our most successful kidney cancer drugs are now immunotherapies. If regression is indeed immune-mediated, it’s a neat idea that our natural body defenses can on their own effectively fight some kidney cancers.
Active surveillance (AS) is a reasonable treatment strategy for SRMs, but this is not always acceptable to patients. What do you think patients need to understand about SRMs and AS that they might not currently?
Regardless of the underlying mechanism, spontaneous regression is a real clinical phenomenon that occurs more frequently than previously thought. This phenomenon further underscores the general indolence of early stage kidney cancers, and provides new additional support for the idea that many of these tumors can be safely observed without the need for invasive treatments.
When patients hear the word “cancer”, it is almost instinct to want to “throw the kitchen sink” at it, that is, to do whatever treatment necessary. It’s a newer understanding that both doctors and patients are becoming more used to, that is, realizing that treatment is not always needed. We are getting better at knowing when that is the case.
What do you think other clinicians need to understand about SRMs and AS?
I would just echo my last point above. Clinicians need to understand that many early stage kidney cancers are not aggressive and that the treatment risks (as low as they are) often outweigh the cancer risk. Many of these early stage cancers grow very slowly or stop growing completely, and now we can add to this understanding that some even spontaneously regress to variable degrees in the absence of treatment. To me, this is all the more reason to hold off treatment until it looks to be imminently necessary.
What motivates you?
I had personal reasons for pursuing a career in urology and cancer medicine and research, related to losing my father to prostate cancer and my mother being a cancer survivor. This experience continues to motivate me.