Proffered paper session 2: GU Tumours non-prostate

Dr Jérémy Blanc, medical oncologist in training at the Jules Bordet institute in Brussels discusses the key results of four clinical trials that were presented during the second proffered paper session on non-prostate genitourinary cancers at ESMO 2024.

The objective of the randomised phase III JCOG1019 study was to evaluate the feasibility of a watchful waiting (WW) strategy in patients with high-grade pT1 (HGT1) non-muscle invasive bladder cancer (NMIBC). The study included a total of 513 patients who underwent a complete eradication of all visible bladder tumours using a transurethral resection (TUR) and had a histopathological diagnosis of HGT1 bladder cancer. After the 1st registration, patients underwent a 2nd TUR and entered the second phase of the study if the specimens showed pT0 disease. These 263 patients were subsequently randomised to WW or intravesical BCG for 8 weeks.1 After a median follow-up of about 7 years, WW proved to non-inferior to BCG in terms of recurrence-free survival (RFS, HR[90%CI]: 0.692[0.443-1.082] [<1.60)]; one-sided p-value for non-inferiority: 0.001). Also with respect to overall (OS) and metastasis-free survival (MFS) the study did not show a difference between the two treatment arms. As such, these data support WW as a potential standard of care for patients with HGT1 NMIBC without residual disease after a second TUR.

In the TOMBOLA study, researchers evaluated the use of serial circulating tumor DNA (ctDNA) testing to select bladder cancer patients who will benefit from early post-cystectomy immunotherapy. In this Danish study, patients who were receiving neoadjuvant chemotherapy and a radical cystectomy (RC) for non-metastatic, muscle invasive bladder cancer (MIBC, cT2-4aN0-1M0) were monitored with serial tumour ctDNA testing in the postoperative period. In patients who became ctDNA positive during this period, adjuvant therapy with atezolizumab was initiated. Patients who remained ctDNA negative did not receive any adjuvant therapy. Of the 179 patients in the study, 93 (56%) tested positive for ctDNA at any point during the postoperative period (75% during the first 4 months). Adjuvant atezolizumab seemed to provide benefit in these ctDNA-positive patients, with a 1-year rate of RFS and OS of 75.2% and 87%, respectively. Of note, among the ctDNA negative patients, only 2 developed metastatic disease. In conclusion, these early data suggest that serial ctDNA measurements following neoadjuvant therapy and a RC is a highly specific method to select non-metastatic MIBC patients that may benefit from adjuvant immunotherapy.

A third study that was discussed consists of the randomized phase II SunRISe-4 trial. This trial compared the combination of TAR-200, an intravesical targeted releasing system designed to provide local sustained gemcitabine within the bladder, with the anti-PD1 antibody cetrelimab (CET) to CET alone as neoadjuvant therapy for patients with MIBC (cT2-T4a N0M0) who are ineligible for or refuse cisplatin-based neoadjuvant chemotherapy (NAC).3 Of note, about 60% of patients in the study were cisplatin eligible. The study met its primary endpoint with a pathological complete response (pCR) rate of 42% with the TAR-200 + CET combination. Interestingly, the pCR with the combination proved to be somewhat higher in patients with an incomplete resection (56%). In the CET alone arm, a pCR rate of 23% was reported.3 In summary, these are the first findings showing a benefit of adding an intravesical targeted release system to immunotherapy in the neoadjuvant treatment of patients with MIBC.

The final study presented by Dr Blanc assessed the combination of nivolumab and trimodality treatment (TMT: TUR plus Chemoradiotherapy [CRT]) as a bladder-sparing treatment option for patients with non-metastatic MIBC. In the study, non-metastatic MIBC patients with stage cT2–T4a N0M0 disease who previously underwent an optimal TUR were randomized to receive nivolumab (240 mg q2w) concurrently to CRT followed by 6 cycles of nivolumab (480mg q4w) or CRT alone. The addition of nivolumab to TMT significantly increased the bladder cancer free survival (68.6% vs. 42.7% at 2 years, p= 0.021) and OS (88.6% vs. 62.3% at 2 years, p= 0.013), without increasing the rate of grade ≥3 toxicity.4 As such, these findings warrant the further evaluating of this treatment modality in a a randomized phase III trial.