SUO 2020: Our Obligation to Clinical Trials: Urologists and SWOG
Dr. Thompson began by discussing the context of national clinical trials infrastructure, as it relates to the national clinical trials network sponsored by the National Cancer Institute. The National Clinical Trials Network (NCTN) comprises a number of groups that collaborate, including SWOG, Alliance, NRG Oncology, ECOG-ACRIN, COG, and others.
SWOG currently has almost 1200 member sites with 37 active trials. Dr. Thompson then reviewed the history of SWOG, beginning in 1956 when it was founding as the Southwest Cancer Chemotherapy Study Group to test treatments of childhood leukemia. In the context of GU care, Bacillus Calmette Guerin (BCG) was examined and led to this becoming the standard of care for patients with non-muscle invasive bladder cancer. In 2005, the biospecimen bank was established and now contains nearly one million samples. Currently, the SWOG network comprises more than 1000 institutions with more than 12,000 members including physicians, advocates, scientists, nurses, and others. Further, the Hope Foundation has provided more than $30 million in funding to support both clinical research and education.
However, the impact of SWOG, as Dr. Thompson highlighted, can be better appreciated when considering that SWOG trials have led to the approval of 14 new cancer drugs, changed the standard of care more than 100 times, and saved more than 3 million years of human life, according to estimates from Dr. Joseph Unger, PhD.
Dr. Thompson then highlighted SWOG trials which have impacted the care of patients with urologic malignancies, on an organ-site basis. He first began highlighting data among patients with advanced prostate cancer with emphasis on studies of intermittent versus continuous ADT in patients with M1 disease; of docetaxel and estramustine vs docetaxel and prednisone; leuprolide with or without flutamide; and orchiectomy with or without flutamide. Moving earlier in the disease process, he highlighted the SELECT trial of supplements in patients at risk of prostate cancer; S8794 which examined the role of adjuvant radiotherapy; Prostate Cancer Prevention Trial (PCPT) of finasteride on the development of prostate cancer, as well as many subsequent papers from this cohort.
He then transitioned to highlighting SWOG trials of influence in bladder cancer, including those assessing the role of neoadjuvant chemotherapy prior to cystectomy for locally advanced bladder cancer and the role of BCG (both in comparison to other intra-vesical agents and in terms of maintenance regimes) in non-muscle invasive disease.
He then emphasized a few SWOG-led trials in kidney cancer. Most notable among these are nearly a dozen trials of phase III trials of promising agents which proven ineffective and the classic Flanigan paper assessing the role of cytoreductive nephrectomy in the interferon-era. As these trials in kidney cancer particular demonstrate, these trials have been important not just in finding approaches that are effective but excluding those that do not work.
Dr. Thompson then highlighted a number of completed trials that are currently awaiting results. Chief among these are S0931 assessing the role of adjuvant everolimus for high-risk kidney cancer and S1011 of extended versus limited node dissection at the time of cystectomy for muscle-invasive bladder cancer.
S1011 particularly highlights the role of SWOG as a multidisciplinary organization including urologists which can address study questions that may not be of interest to pharmaceutical companies. Further, S1216, examining orteronel in patients with newly diagnosed metastatic castration sensitive prostate cancer represents potentially another new standard of care in this rapidly evolving disease space.
Additionally, S1500 will provide phase II data in papillary renal cell carcinoma (RCC) which is relatively understudied compared to clear cell renal cell carcinoma.
Dr. Thompson then highlighted a number of ongoing trials that are still accruing.
Among these S1602, the PRIME trial, assessing intravesical Tice BCG vs intravesical Tokyo BCG vs intravesical Tokyo BCG with t-cell priming using intra-dermal Tokyo BCG, has relatively rapidly accrued, in spite of COVID-19 and is anticipated to close in December 2020. In contrast to an anticipated 25 patients monthly, nearly 30-40 per month have been recruited. This trial in particular will have rapid clinical impact given the ongoing shortages of Tice BCG.
Next, Dr. Thompson highlighted a few trials which are due to open soon.
Among these, S1931 again highlights the multi-disciplinary care possible within a collaborative group trial. This study, in parallel to the Flanigan trial of past eras, will address the role of cytoreductive nephrectomy among patients receiving checkpoint inhibitor-based systemic therapy regimes.
Dr. Thompson then discussed the importance of collaboration between cooperative groups and emphasized that, within SWOG, there are champions for various trials led by other cooperative groups.
Within SWOG, the GU committee membership encompasses a total of 249 members currently, including urologists, medical oncologists, radiation oncologists, pathologists, biostatisticians, PhD scientists, dietary medicine, cancer prevention, radiology, epidemiology, surgical oncology, and patient advocates. Further, subgroup represented includes translational medicine, radiation oncology, imaging (including radiomics), pathology, a SPORE liaison, early therapeutics, cancer control, oncology research professional nurses, data coordinators, CRA liaisons, pharmaceutical science expertise, patient advocates, and a protocol coordinator. Additionally, there are organ site chairs with joint medical oncology and urology expertise for each of bladder, prostate, and kidney cancer.
Beyond the conduct of specific trials, Dr. Thompson emphasized the role of SWOG in funding for both research support and early career development. In addition to financial support, career development opportunities include grant writing workshops and a fellowship program.
Dr. Thompson then provided the perspective of many involved in SWOG as to why it’s important to have urologists engaged. Dr. Neeraj Agarwal, a medical oncologist, emphasized that urologist involvement facilitates access to the tumor tissue necessary to biomarker development. Further, urologists are often the first point of contact for a patient newly diagnosed with a urologic cancer. Early emphasis on the importance of clinical trials may be critical for ongoing engagement and may make patients more receptive to actual enrollment in the future. Mr. Rick Bangs, a patient advocate concurred with the importance of urologists as “gatekeepers”. Dr. Monty Pal highlighted that urologists may assist with the referrals necessary for appropriate accrual, even to trials that are not specifically surgically focused.
Dr. Peter Black emphasized the importance of SWOG as a training group for clinical trialists in urology given that this may be lacking in our clinical training compared to medical oncologists. Further, surgical questions, and those relating to care that is almost solely within the purview of the urologist, may be best addressed in such cooperative group trials as they are less likely to be prioritized in pharmaceutical funding mechanisms.
Finally, Dr. Tom Flaig emphasized both the quality of work and enjoyment derived from participating in multi-disciplinary teams as an important reason to consider this approach.
In closing, Dr. Thompson highlighted that for many of the thousands of patients we see each year, the optimal treatment approach is not clear. The goal of the SWOG GU committee is to change the standard of care such that patient outcomes are improved. In his view, the SWOG mechanism is the “most merit-based, democratic process to prioritize large, phase III clinical trials”. In particular, the GU committee has a focus on incorporating young investigators who are paired with more senior colleagues. Utilizing the example of PCPT, he highlighted the number of spin-off analyses which have been possible.
While clearly, SWOG cannot sponsor all potentially relevant studies, Dr. Thompson laid out the RFA process emphasizing that this prioritization of concepts based on their merits with the highest priority receiving support.
Presented by: Ian Murchie Thompson, Jr., MD, Professor Emeritus, University of Texas Health Science Center San Antonio, TX
Written by: Christopher J.D. Wallis, MD, Ph.D., Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee @WallisCJD on Twitter at the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC