ASCO 2023 was a ton of fun and lot of learning. In the coming weeks, I’ll share select abstracts that I thought were most important. This article discusses data from a groundbreaking PROSPECT trial which was presented as a Plenary topic at Chicago and published in NEJM last week. Ultimately, this creates more treatment options for rectal cancer patients.
A Revolutionary Paradigm Shift to Rectal Cancer Treatment: Insights from the PROSPECT Trial
Modern medicine is ever evolving, providing us with innovative therapies and treatment approaches that are continuously improving patient outcomes. One of these developments lies within the field of colorectal cancer, specifically in the management of locally advanced rectal cancer. A recent clinical trial, named PROSPECT (Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients with Locally Advanced Rectal Cancer Undergoing Surgery), offers a unique paradigm shift in treatment consideration for patients with intermediate-risk rectal carcinoma.
A new avenue for rectal cancer treatment
For decades, chemoradiotherapy followed by surgical resection has been the gold standard in North America for treating locally advanced rectal cancer. This approach has effectively reduced the risk of disease recurrence in the pelvis to less than 10%. However, while this treatment method is effective, it comes with potential short and long-term toxic radiation effects that can impact patients’ quality of life.
Inspired by previous studies that highlighted the efficacy of the FOLFOX regimen (a combination of fluorouracil, leucovorin, and oxaliplatin) in prolonging disease-free survival, researchers proposed a radical shift in treatment protocol. The PROSPECT trial hypothesized that using neoadjuvant FOLFOX as an initial treatment, with chemoradiotherapy reserved ONLY for those who showed poor response (response < 20%) or could not tolerate at least 5 cycles of FOLFOX, would prove just as effective in preventing disease recurrence to standard of care upfront chemoradiation. All patients went to surgical resection.
Promising findings from the PROSPECT trial
The multicenter, unblinded, noninferiority, randomized trial involved 1,194 patients and spanned from 2012 to 2018. The researchers found that preoperative FOLFOX was noninferior to preoperative chemoradiotherapy in terms of disease-free survival. Among those treated with neoadjuvant FOLFOX, an astonishing 90% were able to avoid receiving chemoradiotherapy without compromising local recurrence rates, pathologic response, and long-term overall survival. Amazingly, the local recurrence risk was less than 2% in either group.
Implications for patient care
The results of the PROSPECT trial provide a new and potentially less toxic approach for treating patients with intermediate-risk mid to upper locally advanced rectal cancer, particularly those who are candidates for sphincter-sparing surgery. This methodology allows a substantial number of patients to avoid the adverse effects of chemoradiotherapy without compromising the rate of disease-free survival.
Tailoring treatments and looking ahead
The emerging evidence from the PROSPECT trial offers a promising avenue for the development of personalized treatment strategies. Avoiding overtreatment and focusing on reducing toxic effects are primary goals that will significantly enhance patients’ quality of life and post-treatment outcomes.
Furthermore, patients and physicians can now work together to tailor treatments based on individual risk profiles and personal preferences. With ongoing advancements in this field and the increasing number of treatment options available, the future for patients dealing with rectal cancer is bright and filled with hope.
Despite the excitement around these groundbreaking findings, it is crucial to understand that these outcomes apply to specific “intermediate-risk” patient populations with mandated tumor-response reassessments at 3 months. More research is needed to assess the generalizability of these findings to high-risk patients.
The following general approach reflects my thoughts for how I think about rectal cancer patients in the clinic:
- T1/T2N0 or Upper Rectal T3N0 – upfront resection then adjuvant chemotherapy if >T3 or N+ with or without ctDNA?
- MSS T2N1, T3N0, T3N1 Upper-Mid Rectal – PROSPECT approach upfront chemotherapy x 3 months then surgery for good responders greater than 20%. If intolerant to chemo or poor response less than 20%, then neoadjuvant chemoradiation followed by surgery. Consider further adjuvant chemotherapy based on ctDNA?
- MSS T2N1, T3N0, T3N1 Upper-Mid Rectal – History of neuropathy or attempting to avoid intravenous chemotherapy, perhaps no dedicated colorectal team or surgeon to reliably assess response in 3 months chemo – 1. TNT with short course? or long term radiotherapy upfront (OPRA, RAPIDO). 2. Chemoradiation followed by surgery/adjuvant chemotherapy
- MSS T4 or N2 or Low-lying or nonoperative management – Total Neoadjuvant Therapy (TNT) with chemoradiation followed by chemotherapy with FOLFOX or FOLFOXIRI (PRODIGE, RAPIDO, OPRA)
- MSI Locally-advanced – Immunotherapy x 6 months. TNT if no response followed by resection.
The PROSPECT trial has significantly widened the therapeutic options for rectal cancer treatment. By demonstrating the noninferiority of neoadjuvant FOLFOX with selective use of chemoradiotherapy, this research offers a less toxic yet effective treatment alternative for patients battling intermediate-risk locally advanced rectal cancer. As always, please consult with your healthcare professional about your treatment options and what is best for your specific case
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.
As one of the principal investigators at his cancer center, Dr. Thomas plays a pivotal role in advancing medical knowledge through his involvement in numerous clinical trials. These trials encompass a spectrum of cutting-edge treatments, including targeted therapy, immunotherapy, intra tumoral therapy, and complex cellular therapies. His commitment to research and innovation underscores his dedication to offering the most effective and up-to-date treatment options to his patients.
Embrace the opportunity to engage with Dr. Sajeve’s expertise, and feel empowered to explore the vast expanse of oncology with renewed curiosity and understanding on “Ask MedOnCMD“