(UroToday.com)Dr. Baumann presented on the role of Radiation Therapy in Oligometastatic and Locally Recurrent Urothelial Carcinoma, as part of this session on Multidisciplinary Care in Early- and Late-Stage Urothelial Cancer.
He set the stage by wanting to talk about 4 clinical scenarios:
- Local Recurrence – Prevention of Local Recurrences/Role of Adjuvant RT
- Local Recurrence – Salvage RT
- Oligometastatic Disease – Metastasis directed therapy
- Oligometastatic Disease – Radiation tot the Primary tumor
Local Recurrence – Prevention of Local Recurrences/Role of Adjuvant RT
The rationale for adjuvant radiation is the following:
- High rates of loco-regional failure (LF) for pT3-4 N0-N+ disease – 20-41% at 5-years from many modern cystectomy series
- Chemotherapy did NOT reduce risk of LF in SWOG 8710 or EPRTC/MRC trials
- LFs are rarely salvageable and associated with poor median survival (9 months)
- Adjuvant RT using modern techniques are well tolerated in prospective series with excellent local control
The below data summarizes some of the data on adjuvant RT in this setting:
As seen above, locoregional control (even in these series of patients with negative surgical margins at the time of surgery) was improved to 96% from 69%. These trials were not powered for DFS and OS, but they suggest potential benefit.
He suggests that adjuvant RT should be considered more often in patients with poor surgical pathology, especially in resource poor countries where adjuvant IO therapy may not be an option. The question now becomes how do we incorporate adjuvant RT in conjunction with adjuvant IO therapy.
Based on the above data, adjuvant RT has been included in the NCCN guidelines – for patients with pT3-4, N+ or positive surgical margins at the time of cystectomy.
He also briefly highlighted the fact that for squamous cell carcinoma of the bladder, which is not response to systemic therapy – adjuvant RT improved OS vs. gem/cis x 4 cycles in a study by Zaghloul et al. (ASTRO 2019). No difference between chemoRT vs. adjuvant RT alone.
Looking at anatomic sites to treat, he reported on his teams work on looking at sites of failure.
As expected, most were in the nodal chains and pelvic side walls. Lesser extent in the cystectomy bed.
As such, a consensus panel (of urologists and radiation oncologists) of the NRG recommended the following contouring atlas for adjuvant RT – defined cystectomy bed, pelvic nodes and key organs at risk (urinary diversion).
* The 2016 consensus recommended treating pelvic nodes and omitting cystectomy bed for margin negative patients.
* The 2022 consensus recommends including cystectomy bed for pT3-4 disease regardless of margin status as new data suggests slightly higher rates of failure in the bed and that toxicity is minimal.
IMRT does allow for good sparing of the bowel and the urinary diversion.
Local Recurrence – Salvage RT
In the setting of primary RT for bladder cancer:
- For Bladder recurrences: No role of re-irradiation. Surgery is preferred.
- For pelvic nodal relapses: Salvage RT reasonable to consider especially if failure is outside of high-dose prior treatment fields.
- But question is SBRT to gross disease OR elective nodal IMRT with boost to involved nodes?
- Unfortunately this data is limited in bladder cancer – but extrapolating from prostate cancer, nodal approach may be associated with less failure
In the setting of primary surgery (cystectomy):
- Salvage RT challenging because more small bowel in the field, limiting dose escalation
- Gross disease needs 60+ Gy – but Small bowel tolerance is ~54 Gy
- For nodal recurrences, he now favors using adjuvant RT treatment volumes and boosting involved nodes to a higher dose
- SBRT is also an option
Oligometastatic Disease – Metastasis directed therapy
Obviously, here he started by bringing up SABR-COMET study, which was a randomized Phase II trial of best systemic therapy +/- SVRT to all mets in patients with oligometastatic solid malignancies (n = 99).
- 5 year OS 42% vs. 17% in favor of SBRT to mets
- 13 month improvement in OS
In this study, unclear how many bladder cancer patients were included (in the “Other” Category)
Role for comprehensive SBRT for oligometastatic urothelial cancer is NOT well defined – but, some retrospective studies show some benefit for MDT with SBRT or metastasectomy.
- Combination with IO intriguing due to potential added benefit from an abscopal effect in select patients
He highlighted a few small retrospective series, which were favorable. However, large specific trials are needed.
Oligometastatic Disease – Radiation to the Primary tumor
STAMPEDE trial for prostate cancer increased interest in primary RT for GU malignancies – but no prospective data exists for definitive local therapy to the bladder for oligometastatic disease.
Multiple retrospective series suggest an overall survival benefit – but studies limited by selection bias and potential confounding.
At this time, there is no good prospective data and is not part of guidelines. But it is hypothesis generating and perhaps lays groundwork for a trial of local therapy.
Presented by: Brian Christopher Baumann, MD, Washington University School of Medicine
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.