Wassim Kassouf, MD, on Whole Pelvis Radiation in Muscle-Invasive Bladder Cancer
– Expanding radiation volume associated with improved cancer-specific, overall survival
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For the 40% of patients with muscle-invasive bladder cancer (MIBC) who have micrometastatic nodal occult disease, current management includes either with pelvic lymph node dissection (PLND) or radiation-based therapy, commonly in the form of trimodality therapy.
Since PLND in this setting is often curative in a select group of patients, Ronald Kool, MD, of McGill University in Montreal, and colleagues set out to determine the potential impact on oncologic outcomes of widening the radiotherapy fields to include pelvic lymph nodes, particularly in high-risk patients.
The study, presented at ASCO's , is based on data from 599 patients with urothelial MIBC (cT2-4aN0-2M0) who underwent curative-intent radiation therapy of the bladder only (BO-RT) or of the whole pelvis (WP-RT) between 2001 and 2018 at 10 academic centers. The median follow-up was 34 months.
Multivariable analysis showed that WP-RT did not affect complete response rates post-radiation (OR 1.14, P=0.526). However, in 369 patients who underwent WP-RT, there was a significant improvement in cancer-specific survival (HR 0.66, P=0.016) and overall survival (HR 0.68, P=0.002) compared with those who received BO-RT. This improvement was independent of other prognostic factors.
Patients in the WP-RT group were more likely to be younger, to have clinical node-positive disease, lymphovascular invasion, and to be treated with neoadjuvant chemotherapy and concurrent chemotherapy. Following adjusted inverse probability treatment-weighted analysis, all absolute differences in baseline patient characteristics between the two cohorts were no longer significant, co-author Wassim Kassouf, MD, also of McGill, told 51˶. "Even after balancing the two groups, WP-RT remained associated with improved survival," he said.
In the following interview, Kassouf, who is chair in Urology and head of Urologic Oncology, discussed the findings in greater detail.
What does this analysis add to the literature?
Kassouf: Our study demonstrates that radiation of the pelvis lymph nodes in addition to bladder radiation is associated with improved survival and should be considered in patients with muscle-invasive bladder cancer.
Did any of your findings come as a surprise?
Kassouf: In the surgical literature, it is standard of care to perform pelvic lymphadenectomy along with radical cystectomy in patients with muscle-invasive bladder cancer as it has a therapeutic benefit and is associated with improved survival. If we adopt an organ-preservation radiation-based approach for similar patients, it is of no surprise that treating the pelvic lymph nodes will also yield improved oncologic outcomes. This is especially relevant as we treat more high-risk muscle-invasive bladder cancer patients with organ-preservation approaches.
Any thoughts on why an earlier study did not show significantly improved OS rates with whole pelvis radiotherapy?
Kassouf: The previous randomized study was underpowered due to small sample size. Furthermore, the control arm in which patients received bladder-only radiation incorporated a wider treatment field of at least 2 cm beyond the bladder margin. As a result, some pelvic lymph nodes would have received radiation.
Do you think more patients with MIBC should be offered whole-pelvis radiotherapy?
Kassouf: As trimodal therapy is increasingly being offered to the younger and healthier patients, the increased survival benefit of whole-pelvis radiotherapy becomes more relevant and should be discussed with the patient.
What's next for research in this area?
Kassouf: Future research should target decreasing the rates of salvage cystectomy and improving the survival of patients treated with bladder-preservation therapy, especially since use of this approach is increasing in patients with high-risk muscle-invasive bladder cancer, due to hydronephrosis, a palpable mobile mass, lymphovascular invasion, and so on.
We are also looking forward to the results from several ongoing trials evaluating the impact of adding immune checkpoint inhibition in patients with muscle-invasive bladder cancer receiving trimodal therapy.
Read the study here.
Kool reported relationships with Janssen Oncology and Zodiac Pharma; Kassouf reported relationships with Bristol Myers Squibb, Ferring, Janssen, Merck, Roche, and Sesen Bio; several other co-authors also disclosed relationships with industry.
Primary Source
Journal of Clinical Oncology
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