Metastases-directed local therapies (MDT) beyond genuine oligometastatic disease (OMD): Indications, endpoints and the role of imaging.

To further personalise treatment in metastatic cancer, the indications for metastases-directed local therapy (MDT) and the biology of oligometastatic disease (OMD) should be kept conceptually apart. Both need to be vigorously investigated. Tumour growth dynamics - growth rate combined with metastatic seeding efficiency - is the single most important biological feature determining the likelihood of success of MDT in an individual patient, which might even be beneficial in slowly developing polymetastatic disease. This can be reasonably well assessed using appropriate clinical imaging. In the context of considering appropriate indications for MDT, detecting metastases at the edge of image resolution should therefore suggest postponing MDT. While three to five lesions are typically used to define OMD, it could be argued that countability throughout the course of metastatic disease, rather than a specific maximum number of lesions, could serve as a better parameter for guiding MDT. Here we argue that the unit of MDT as a treatment option in metastatic cancer might best be defined not as a single procedure at a single point in time, but as a series of treatments that can be delivered in a single or multiple sessions to different lesions over time. Newly emerging lesions that remain amenable to MDT without triggering the start of a new systemic treatment, a change in systemic therapy, or initiation of best supportive care, would thus not constitute a failure of MDT. This would have implications for defining endpoints in clinical trials and registries: Rather than with any disease progression, failure of MDT would only be declared when there is progression to polymetastatic disease, which then precludes further options for MDT.

Comparative effectiveness of radical cystectomy and radiotherapy without chemotherapy in frail patients with bladder cancer.

Objectives: To evaluate cancer-specific (CSS) and overall survival (OS) in a group of frail patients who were treated with RT without chemotherapy and to compare them with a matched cohort of patients treated with RC.Methods: This study identified 71 patients treated with RT only for high-risk bladder cancer. Patients with metastatic (cN + or cM+) or non-resectable tumors (cT4) and those who received any form of chemotherapy were excluded. Patients where matched 1:1 using propensity scores which adjusted for the effects of age, clinical stage and age-adjusted Charlson comorbidity index (CCI). OS and CSS were evaluated using the Cox proportional hazards regression model and the Fine and Gray competing risk model.Results: In the overall population, RT was associated with worse OS (HR = 1.78, 95% CI = 1.15-2.77, p = 0.01) compared to RC, but not with CSS (HR 1.1, p = 0.74). In the matched cohort, RT was neither associated with OS nor CSS (p > 0.05) compared to RC. In the competing risk analyses no statistically significant association of any of the treatments was observed in the total or in the matched data set (p > 0.05).Conclusion: The use of RT may be an alternative option in well selected patients with limited disease who are considered unfit for systemic chemotherapy and RC. Future research should focus on improving patient selection and assess the quality-of-life as well as the need for reintervention in patients treated with RT.

PSMA Ligand PET/MRI for Primary Prostate Cancer: Staging Performance and Clinical Impact.

PURPOSE: Primary staging of prostate cancer relies on modalities, which are limited. We evaluate simultaneous [68Ga]Ga-PSMA-11 PET (PSMA-PET)/MRI as a new diagnostic method for primary tumor-node-metastasis staging compared with histology and its impact on therapeutic decisions. EXPERIMENTAL DESIGN: We investigated 122 patients with PSMA-PET/MRI prior to planned radical prostatectomy (RP). Primary endpoint was the accuracy of PSMA-PET/MRI in tumor staging as compared with staging-relevant histology. In addition, a multidisciplinary team reassessed the initial therapeutic approach to evaluate its impact on the therapeutic management. RESULTS: PSMA-PET/MRI correctly identified prostate cancer in 119 of 122 patients (97.5%). Eighty-one patients were treated with RP and pelvic lymphadenectomy. The accuracy for T staging was 82.5% [95% confidence interval (CI), 73-90; P < 0.001], for T2 stage was 85% (95% CI, 71-94; P < 0.001), for T3a stage was 79% (95% CI, 43-85; P < 0.001), for T3b stage was 94% (95% CI, 73-100; P < 0.001), and for N1 stage was 93% (95% CI, 84-98; P < 0.001). PSMA-PET/MRI changed the therapeutic strategy in 28.7% of the patients with either the onset of systemic therapy/radiotherapy (n = 16) or active surveillance (n = 19). CONCLUSIONS: PSMA-PET/MRI can provide an accurate staging of newly diagnosed prostate cancer. In addition, treatment strategies were changed in almost a third of the patients due to the information of this hybrid imaging technique.