Simultaneous Optimization of Organ Transplant Rates, Urologic Cancer Outcomes

To kick off the Society of Urologic Oncology Annual Meeting, Phillip M. Pierorazio, MD, and Scott E. Eggener, MD, moderated a session on simultaneous optimization of solid organ transplant rates and urologic cancer outcomes, including considerations for prostate, kidney, and urothelial, as well as testicular, penile, and adrenal cancers.

Dr. Pierorazio started off with a key take-home goal of the session – that malignancies of low metastatic potential are still malignancies of low metastatic potential in transplant patients.

Kymberly D. Watt, MD, of Mayo Clinic, took to the microphone to discuss historical patterns and modern management of urologic malignancies in solid organ transplant recipients. One year after liver transplant, cause of death is typically nonhepatic (63.3%), with the most common being malignancy (29.5%). As for urologic cancers, all are in the ballpark of 3-times the general population risk for transplant recipients for developing a de novo malignancy, with the exception being prostate cancer (which has a comparable risk).

“We can anticipate a lot more patients coming to transplant with a history of GU malignancy,” she stated, with a possible requirement of different surveillance in some of these cancers (including individuals with immunosuppression). Screening for de novo cancers is vital, she added, and aggressive treatment of post-transplant cancers is needed to improve outcomes, including the use of immunotherapy despite the risk of rejection.

Next, Marc-Oliver Timsit, MD, PhD, of Université Paris Cité, offered updates on GU cancer management before and after transplant for elevated PSA and prostate cancer. Immunosuppression does not fuel prostate cancer, he began, and cited the data to support this statement. Screening for prostate cancer in transplant candidates reduces access to transplant, he continued, highlighting a 2016 analysis in which over 75% of candidates with a positive PSA screening result did not receive a transplant due to “obsolete” guideline recommendations.

In transplant recipients, the options for treating prostate cancer are the same as in the general population. AST guidelines are the first to push barriers based on excellent survival after prostate cancer treatment, Dr. Timsit detailed. Lastly, he acknowledged that while there is an individual benefit of transplanting patients with prostate cancer versus those with dialysis, the matter of organ shortage needs to be addressed as well as “wasting” a scarce resource for a prostate cancer patient likely to survive less than 15 years.

Venkatesh Krishnamurthi, MD, of Cleveland Clinic, took to the podium next to discuss GU cancer management before and after transplant for renal masses and renal cell carcinoma (RCC). He provided a framework for the approach to transplant candidates who are found to have a renal mass or diagnosed with RCC, including a separation of asymptomatic incidental masses and symptomatic masses, as well as those transplant recipients who develop a de novo diagnosis of renal cancer.

He referenced a guidelines panel’s recommendations for renal cancer screening in patients deemed “high-risk.” In patients where a renal mass is identified, a waiting period is listed, but with vague terminology and suggestions.

Then, Dr. Krishnamurthi highlighted a recent systematic review of the risk of tumor recurrence in patients undergoing renal transplantation for end-stage renal disease after previous treatment for a urologic cancer. Within this review, he mentioned a take-home message that “even if you treat the patient at the time of transplant, when there is low-stage renal cancer, there is a very low risk of recurrence.” As for higher-stage disease, the review showed that variables including stage, nodal status, and histopathology play a role in cancer-specific survival.

What is the risk of developing kidney cancer following renal transplant? Dr. Krishnamurthi explained how the risk is 6-times higher for the transplant population than the general population, largely driven by the risk of developing papillary RCC. However, most of these cancers are relatively indolent and can be found at an early stage, he noted. These patients have a slightly higher risk of mortality, he added.

Next up was Piyush K. Agarwal, MD, of the University of Chicago, to cover pre- and post-transplant of bladder cancer. The risk of bladder cancer is elevated in pre-transplant patients, he started, but screening for bladder cancer is not recommended, though occasionally done prior to listing on a transplant registry. The management of these patients is the same as any patient with bladder cancer, he added.

Modifying the waiting period for these patients is paramount, he continued. The Cincinnati Transplant Tumor Registry defined a waiting period of 2 to 5 years, but they did not take into account stage, grade, and distinction between non-muscle invasive and muscle-invasive bladder cancer was not made. In fact, most cancer patients with end-stage renal disease are older and a 2-5 year waiting period leads to death from dialysis burden rather than cancer; a 2018 review of patients with bladder cancer on dialysis demonstrated a cancer-specific survival of 86% to 98%, but an overall survival (OS) of 43% to 88%. A Norwegian study with a waiting period of 1 year demonstrated that kidney transplant recipients with previous malignancy had the same OS and graft survival as kidney transplant recipients without cancer, which suggests that waiting period is not associated with recurrence or overall mortality.

Dr Agarwal then provided a summary of recommendations and evidence for each bladder setting: a 6-month waiting period for non-muscle invasive and low-risk as well as for non-muscle invasive and intermediate risk, a 24-month waiting period for non-muscle invasive and high-risk as well as muscle-invasive after radical cystectomy, and no recommendation given for muscle-invasive treated with trimodal therapy.

Christine O. Ibilibor, MD, MSc, of the University of Virginia, gave a quick overview of the considerations in penile, testicular, and adrenal cancers. Only 1% of urologic cancers in transplant recipients are penile cancer patients, and there is currently no prespecified waiting time for these patients, which means the waiting period needs to be balanced against tumor stage as well as risk of distant recurrence. Testicular cancers are even rarer than penile cancer in the post-transplant setting, though wait time recommendations are provided by KDIGO as at least 2 years for localized disease and 2 to 5 years for invasive disease. As for adrenal cancer—the rarest of all urologic malignancies in transplant recipients—there is no prespecified wait times and it should be a collaborative decision among appropriate parties.

Comparative analyses of surgical outcomes between solid organ transplant recipients with penile, testicular, or adrenal cancer and those without these cancers are limited, she added, noting that standard-of-care surgery is always appropriate in these situations.

Rounding out the session was a discussion on clinical considerations from a urologic oncologist-transplanter: Talal Al Qaoud, MD, FRCSC, of the MedStar Georgetown Transplant Institute. He started with de novo RCC in renal transplant grafts. The risk of graft RCC is much smaller than native kidney RCC, he stated, and the risk factors are immunosuppression, donor age, and longer graft survival.

Dr. Al Qaoud highlighted a case example to highlight that the majority of masses in the renal graft are managed by partial nephrectomy and with similar outcomes to native kidney RCC. Additionally, a majority of patients preserve renal function and avoid returning to dialysis.

Moving on to using kidneys with small renal masses, these are select cases with T1a and low risk of transmission, and there is no difference in outcomes between living donor and deceased donor kidneys with small renal masses. Additionally, there is no consensus on immunosuppression modulation as well as no consensus on surveillance strategy.

As for immunotherapy and immunomodulation, there is more liberal use in kidney cancer because of the back-up option of dialysis. But what is the best agent? It is not clear, and more data is needed for immunosuppression modulation. Prospective studies are needed to better understand the risk factors of rejection and therapeutic targets.