Pamela L. Kunz, MD
Commenting at a press briefing, Pamela L. Kunz, MD, Director of the Center for Gastrointestinal Cancers and Chief of GI Medical Oncology at Smilow Cancer Hospital and Yale Cancer Center, New Haven, said the results of PROSPECT are “practice-changing” and “align incredibly well with the theme at this year’s annual meeting around de-escalation of therapy and partnering with patients.”
Dr. Kunz continued: “What’s important here is that radiation can be safely omitted in many patients with clinically advanced rectal cancer—this is really ‘less is more.’ We can spare select patients from receiving radiation without compromising efficacy. This leads to improved quality of life and reduced side effects, including things like early menopause and infertility.”
Additional Commentary
During the Plenary Session, PROSPECT’s invited discussant, Corrie Marijnen, MD, PhD, Chair of the Department of Radiation Oncology at the Amsterdam Cancer Institute and Professor (Clinical) of Radiotherapy at Leiden University Medical Center in the Netherlands, commented that the trial was well conducted and yielded results that add “another piece in the jigsaw [puzzle] of rectal cancer.” She especially praised the investigators for including patient-reported outcomes, which among many benefits can inform decision-making about treatment.
Corrie Marijnen, MD, PhD
Although the two approaches in PROSPECT yielded similar oncologic outcomes, Dr. Marijnen thought the long-term toxicities and quality-of-life factors “tip the scale” in favor of neoadjuvant chemotherapy with selective use of radiotherapy. She added: “No radiotherapy means no radiotherapy-related toxicity.”
Long-term neuropathy associated with chemoradiotherapy may be more relevant for some patients, such as musicians, whereas the early toxicities associated with modified FOLFOX (fluorouracil, leucovorin, oxaliplatin) may be of most concern to parents of young children. For elderly patients and patients living some distance from the treatment center, radiotherapy may be particularly undesirable, she added. Of note, she emphasized, patient preferences and input must be considered.
Concerns About the Study Population
Dr. Marijnen did have some concerns about the study population. She pointed out that the definition of “locally advanced” rectal cancer varies by region. By some definitions, many of PROSPECT’s patients might be classified as having “early- and intermediate-stage disease,” which would not qualify them for neoadjuvant chemotherapy.
This possibility may explain why the local recurrence rate of less than 2% was much lower than reported in many other studies, she suggested. In a more unequivocally “locally advanced” patient population, she suggested, “modified FOLFOX on its own may not be enough if you want to achieve a complete response….” The growing trend toward a nonoperative approach requires an excellent response, she added.
Dr. Marijnen concluded: “FOLFOX followed by selective chemoradiotherapy may replace standard neoadjuvant chemoradiotherapy in early/intermediate-risk, middle/high rectal tumors. The largest benefit is less long-term radiotherapy-related toxicity. And shared decision-making is advised in all cases.”
DISCLOSURE: Dr. Kunz reported financial relationships with Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and Isotope Technologies Munich SE. Dr. Marijnen reported no conflicts of interest.
