Implementation and outcome of personalized treatment strategies in advanced genitourinary cancers

Outcome is dismal in patients with advanced genitourinary (GU) cancers refractory to standard treatments. Molecular analyses and subsequent discussion of cases in specialized molecular tumor boards (MTBs) are increasingly incorporated into clinical management to facilitate personalized treatment. Data on this approach are lacking for GU malignancies.

We conducted a retrospective analysis of patients with GU cancers discussed in the MTB at the Charité between 2016 and 2023. Ethics approval was obtained for prospective follow-up of patients after written informed consent and for retrospective data analysis. Clinical benefit was defined as complete response (CR), partial response (PR) or stable disease (SD) >6 months or a progression-free survival (PFS) ratio between molecularly matched therapy (MMT) and previous non-MMT >1.3. Outcome was assessed by the investigators.

Among 126 identified MTB patients, most patients had a rare tumor type (n = 59), followed by adenocarcinoma of the prostate (n = 45), urothelial carcinoma (n = 17) and clear-cell renal carcinoma (n = 5). Molecular profiling included immunohistochemistry (n = 80), panel sequencing (n = 110) and/or whole-exome/-transcriptome sequencing (n = 21). Eleven patients died before the final MTB discussion. At least one treatment option for MMT was identified for 78/115 patients (68%). Twenty-five patients were treated with an MMT (22%), three of whom subsequently received a second MMT. Eighteen MMTs were given in an off-label setting and two within clinical trials. A clinical benefit was observed in 8/28 (28.6%) applied MMTs. A PFS-ratio >1.3 was achieved in eight patients. Among patients with rare entities discussed (n = 54), 42 patients had at least one MMT option (78%), with 19 patients receiving at least one MMT (35%).

For a majority of GU cancer patients an MMT was identified and responses were seen in heavily pretreated patients. Additional controlled trials and integration of comprehensive molecular analyses and subsequent personalized therapy should be considered for patients with GU cancers, especially those with rare histologies.