Page 90 - ARNM-3-2

Advances in Radiotherapy
& Nuclear Medicine Radiotherapy in node-positive bladder cancer

48 Gy to nodes and reported that six (38%) of the patients received upfront atezolizumab. The median number of
had grade 1 and 2 lower toxicities after IMRT, while no cycles administered was three, and patients were reviewed
grade 3 and 4 toxicities were reported in this study. after the completion of chemotherapy to ensure they had
The role of pelvic RT in MIBC has also been evaluated no significant residual toxicity before commencing RT.
in the adjuvant (post-operative) setting. In a multicenter NAC targets micrometastatic disease and may reduce
19
phase 2 trial by Fonteyne et al., 17 patients received primary tumor volume after incomplete TURBT, while
IMRT, delivering 50 Gy in 25 fractions to the tumor bed also improving the OS and DFS rates. In the BA06 study,
and pelvic nodes. Acute grade 2 GI toxicity was observed NAC with cisplatin, methotrexate, and vinblastine was
in 62% of patients, while 4% developed acute grade 3 GI administered, followed by either cystectomy or RT. The
toxicity. One patient had grade 5 diarrhea and vomiting trial reported a 16% reduction in the risk of death, with
due to obstruction after 1 month. In a trial by Murthy the 3-year survival rate increasing from 50% to 56% in
10
et al., 18 patients were treated to the tumor bed and pelvic favor of NAC. Before cystectomy or RT, platinum-based
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node to 50.4 Gy in 28 fractions, and they reported that RT neoadjuvant combination chemotherapy has demonstrated
to the lymph nodes increased DFS from 70% to 85%. the potential to deliver a 5% absolute OS benefit and a 9%
DFS benefit at 5 years. 21
The present study describes a novel hypofractionated RT
dose-fractionation schedule (57.5 Gy to the primary tumor The use of induction SACT was associated with a
and 46 Gy in 23 fractions to the nodes) using VMAT for significant prolongation of OS rate in patients (median
treating bladder and pelvic nodes in patients with MIBC. OS: 40.1 vs. 13.6 months; HR: 0.16; 95% CI: 0.02 – 1.12;
To our knowledge, this protocol has not been reported p=0.002). The survival benefit was much higher than
previously. The development of the protocol was based on those reported in previous studies. However, the results
sound radiobiological modeling with a BED equivalent to may be skewed in favor of SACT due to two patients (6%)
a hypofractionated schedule of 55 Gy in 20 fractions (α/β who had a prolonged duration of immunotherapy before
value of 10), with similar probabilities of tumor control. proceeding with RT.
The BED for late toxicity in the new protocol (with an Most patients in our study cohort also received
2Gy
α/β value of 2 for late-responding tissues) was 64.68 Gy, concurrent chemotherapy with a single agent, either
compared to 65.3 Gy for the hypofractionated schedule of gemcitabine or cisplatin – the most commonly employed
55 Gy in 20 fractions. Therefore, it was hypothesized that regimens. Most of the acute toxicities reported were
the use of the new protocol of 57.5 Gy in 23 fractions would grade 1 or 2, including fatigue, diarrhea, pain or local
be associated with similar levels of tumor control and discomfort, increased frequency of micturition, and
toxicity as the hypofractionated schedule of 55 Gy in 20 dysuria. One patient (6%) had a grade 3 acute toxicity
fractions. In MIBC, pelvic RT is often administered using event (pain and local discomfort), and two patients (17%)
conventional fractionation, which uses 46 – 48 Gy to target experienced grade 3 late toxicity events (colovesical fistula
the nodes and 60 – 64 Gy to target the primary tumor. and severe radiation-induced cystitis). The retrospective
A recent meta-analysis of patients with localized MIBC nature of the study limits the accurate assessment of
found that hypofractionated RT was linked to improved toxicities. Nonetheless, the toxicity rates reported in our
locoregional control as compared to conventional study are consistent with those reported by other studies.
fractionation. Therefore, a hypofractionated pelvic RT In our study, 70% of patients (n = 12) had a complete
technique may offer benefits in terms of promoting response or stable disease after CRT completion. More
effective local control. than 50% of patients (n = 9) remained disease-free at the
Six patients (35%) in the study cohort had major last FU, with 47% (n = 8) developing disease progression
comorbidities, and two patients (12%) had adverse (local progression, n = 2; metastatic progression, n = 6).
histology with neuroendocrine transformation, making The median PFS was 15.8 months. Seven patients (41%)
them a prognostically unfavorable group of patients. were alive and well, with no signs of recurrence, and the
9
A total of 15 patients (88%) had evidence of clinically median OS was 23.1 months (95% CI: 13.6 – 64.6).
node-positive disease, and two patients (12%) received Our results indicate that the VMAT protocol of 57.5 Gy
elective nodal irradiation in the presence of high-risk in 23 fractions prescribed to the bladder and primary
MIBC. Ten patients (59%) received SACT with platinum- tumor, as well as 46 Gy in 23 fractions to the pelvic lymph
based doublet combination chemotherapy – the most nodes, can be safely delivered along with concurrent
commonly employed regime (n = 8). One patient (6%) chemotherapy. This protocol resulted in minimal clinically
received cisplatin/gemcitabine chemotherapy followed by significant grade 3 toxicity and an approximately 70%
maintenance pembrolizumab, and another (3%) patient response rate, including a 41% complete clinical response

Volume 3 Issue 2 (2025) 82 doi: 10.36922/ARNM025090009