Research Update: Spontaneous Tumor Regression
Dr. Eric Kauffman received a Kidney Cancer Association Research Award in 2021 for a project called “Biology of spontaneously regressing renal cell carcinoma primary tumors” that looked at how and why some kidney tumors shrink on their own, without treatment.
Here, KCA’s Chief Scientific Officer, Dr. Salvatore La Rosa, shares some recent updates and learnings from Dr. Kauffman’s research.
A rare but fascinating phenomenon sometimes occurs in kidney cancer. For a small number of patients, their tumors can shrink on their own, without any treatment.
This is called primary tumor spontaneous regression (PT-SR). A KCA-funded study led by Dr. Eric Kauffman at Roswell Park Cancer Center set out to better understand why PT-SR happens and whether we can learn to predict it or even encourage it in more patients.
Kauffman and his research team compared people whose kidney tumors shrank during active surveillance – a period of closely monitoring a kidney cancer diagnosis without immediate surgery or treatment – with people whose tumors continued to grow.
By analyzing both tumor tissues and blood samples, the researchers looked closely at the kinds of immune cells present – especially T cells, the body’s cancer-fighting soldiers and recently reported some interesting findings.
In some kidney cancers, they found that tumors that shrank more had many more of certain types of anti-cancer T cells and macrophage clusters than tumors that did not shrink. In another type of kidney cancer, tumor shrinkage seemed related to changes in blood supply, possibly more so than immune alterations.
In blood samples, people who had PT-SR had many more of certain T cell types that suggest their immune systems were better prepared to attack the tumor even before shrinkage began.
We spoke with Kauffman again to get an update about his research project.
KCA: Previously, you observed that 1 in 5 of your active surveillance patients experience PT-SR. Is that still the case?
Kauffman: Our latest PT-SR study update was reported at the American Urological Association’s annual meeting in Las Vegas in May 2025. Of note, this was the largest series of biopsy-confirmed RCC patients on active surveillance reported to date (n=182), to my knowledge.
In this updated analyses, we found the incidence of PT-SR to be about 1 in every 4 biopsy-confirmed RCC patient on active surveillance. This incidence is a bit higher than our initial study identified (1 in every 5), likely because our patient cohort has been on surveillance longer, and the duration on surveillance appears to be significantly associated with PT-SR. That is, the longer a patient is on active surveillance, the more likely that PT-SR occurs.
The subtype of the RCC tumor is important when considering PT-SR incidence. In particular, PT-SR is quite common in papillary RCC and chromophobe RCC patients (including over 40% of patients) but rather infrequent in clear cell RCC patients (about 10%). Patients with more than one RCC tumor (including a history of prior surgery for a different RCC tumor) also have significantly higher rates of PT-SR.
KCA: Can you clarify the extent of natural regression observed in PT-SR patients – how can we visualize the changes in size?
Kauffman: By our own definition, all PT-SR have at least 30% size (volume) reduction, which can be subtle (e.g., a large grape vs. a small grape). That said, most of our PT-SR cases had greater than 50% size reduction, with the median being close to a 60% size reduction. This extent of regression is comparable to, say, a strawberry that reduces to the size of a large grape; or an average-size grape that reduces to the size of a blueberry.
The subtype of the RCC tumor makes a big difference in not only how often it regresses, but also to what extent it regresses. For example, chromophobe RCC not only regresses the most frequently, but it also typically has major (over 70%) size reduction – such as a strawberry shrinking to a blueberry – while clear cell RCC tends to have only minor (30-50%) volume reductions, and papillary RCC tends to fall somewhere in between (50-70%).
On occasion, we have observed chromophobe or papillary RCC cases to regress completely without subsequently re-growing, which is exciting!
KCA: Is PT-SR temporary and the tumor will begin to grow again? Or does a patient who experiences PT-SR then have a tumor that will regress, stabilize, or have a reduced growth rate indefinitely?
Kauffman: It varies. Some patients stabilize at a “trough” size while others have gradual return of growth after reaching a trough. Only about 1 out of every 5 PT-SR cases grow all the way back to the original size that it was prior to regression. When this happened in our patients, it usually took at least a couple years after the start of PT-SR for the tumor to grow back to its original peak size. If these tumors continued to keep growing, they often needed to be treated.
KCA: Do patients who experience PT-SR eventually need surgery or treatment for their tumors? Is their treatment much different from people who don’t experience PT-SR?
Kauffman: We have found that patients with PT-SR are significantly less likely to need treatment (i.e., surgery or thermal ablation). As mentioned, some PT-SR patients experience rebound growth during active surveillance, which may eventually require treatment.
Our latest analyses looked at whether the occurrence of PT-SR reduces the likelihood of eventually needing treatment. In the absence of PT-SR, most (over 50%) of biopsy-confirmed RCC patients on active surveillance needed treatment within 5 years. In contrast, only a minority (less than 20%) of RCC patients needed treatment within 5 years if they experienced PT-SR at any point.
KCA: What is the main takeaway you’d like to leave patients and families with from your research?
Kauffman: When diagnosed at a small size, RCC kidney cancers are often very non-aggressive and a notable portion even regress spontaneously if treatment is deferred, particularly the non-clear cell subtypes of RCC. We are still learning why this happens so that we can make better recommendations to early stage RCC patients as to whether or not they need treatment, and also to help us come up with new types of treatments to fight off these cancers.
We congratulate Dr. Kauffman again on receiving a KCA grant and are grateful for his detailed explanation here of what his research on spontaneously regressing tumors has uncovered thus far.
While PT-SR is cause for hope and continued research, it’s still very uncommon, affecting only a minority of people. Most kidney tumors will not shrink by themselves. People who experience PT-SR still require ongoing surveillance and many will need treatment eventually.
But understanding how the immune system is involved in cases of PT-SR helps us better care for people with kidney cancer. Kauffman’s study analyzed the exact types and activation states of the T cells inside primary kidney tumors, offering a roadmap for future therapies. If doctors can identify patients whose immune systems are already primed to shrink tumors, those patients might safely avoid unnecessary treatment.
Even more exciting, scientist could work on ways to actively “prime” or otherwise manipulate the immune systems of other patients to mimic this natural tumor regression. This opens the door to new treatments that use your own body’s defenses to fight cancer.
As research continues, these discoveries move us closer to a future where kidney cancer is not just watched through “active surveillance” but actively overcome.