EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Imaging treated prostate cancer.

In patients with a clinical suspicion of recurrence after treatment for prostate cancer, imaging can be used to distinguish between local recurrence and metastatic disease. Multiparametric magnetic resonance imaging (mpMRI) of the prostate may be a valuable imaging modality for the detection and localization of local recurrence in patients treated for prostate cancer. In mpMRI, morphological T2-weighted images are combined with functional MRI techniques including diffusion-weighted imaging, dynamic contrast-enhanced imaging, and magnetic resonance spectroscopic imaging to improve accuracy. In this paper, the current status of imaging techniques used to detect and to localize tumor recurrence in patients treated for prostate cancer will be reviewed, with emphasis on mpMRI for local prostate cancer recurrence.

Complications of bone tumors after multimodal therapy.

PURPOSE: To define and compare the complications of bone tumors after resection, extracorporeal irradiation and re-implantation, with or without radiotherapy. MATERIALS AND METHODS: Eighty patients (40 males and 40 females, ages 4-77 years) with 61 malignant and 19 benign bone tumors were evaluated for local and distant complications after treatment. Two groups of patients were studied: (1) 53 patients had resection without (43 patients) or with external beam radiotherapy (RadRx) (10 patients) and (2) 27 patients underwent extracorporeal irradiation and re-implantation without (22 patients) or with RadRx (5 patients). Patient follow-up varied from 1 month to 13.63 years with mean follow-up of 4.7 years. Imaging studies included bone and chest radiography, spin echo T1- and T2-weighted (or STIR) magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography (CT) for thoracic and abdominopelvic metastases and 3-phase technetium-99m-labeled-methylene-diphosphonate (Tc99m MDP) scintigraphy for bone metastases. RESULTS: DCE-MRI differentiated the rapidly enhancing recurrences, residual tumors and metastases from the slowly enhancing inflammation, and the non-enhancing seromas and fibrosis. Recurrences, metastases (mainly to lung and bone), and seromas were greater than twice as frequent in patients after resection than after ECCRI. Although 11.3% of post-resection patients had residual tumor, no ECRRI-treated patient had residual tumor. In contrast, after ECRRI, infection was almost three times as frequent and aseptic loosening twice as frequent as compared with the post-resection patients. Bones treated with RadRx and/or ECRRI showed increased prevalence of fractures and osteoporosis. In addition, muscle inflammation was more common in the externally irradiated patient as compared with the patient who did not receive this therapy. However, another soft tissue complication, heterotopic ossification, was rare in the patient after RadRx, but 25.6% of patients after resection and 40.9% after ECRRI showed heterotopic ossification. Unusual complications after resection or ECRRI involved adjacent nerves with partial denervation, amputation neuroma, or entrapment (secondary to recurrence or fibrosis) after resection or ECRRI with or without RadRx. One patient developed a posterior tibial artery pseudoaneurysm after ECRRI. CONCLUSIONS: Follow-up of patients with benign and malignant bone tumors demonstrated the efficacy of DCE-MRI for distinguishing rapidly enhancing viable tumor from the slowly enhancing or non-enhancing benign processes after different therapies. Although recurrences, residual tumors, metastases and seromas were more common after resection, fractures, osteoporosis, infection, and muscular atrophy predominated in the ECRRI-treated patient. RadRx further predisposed post-resection and post-ECRRI patients to develop fractures, osteoporosis and infection and was the major cause of persistent muscle inflammation at MRI. Because complications can evolve and resolve years after treatment, the patients with bone tumors, particularly sarcomas, must receive life-time multimodal imaging for maximal diagnosis and treatment.

Post-treatment complications of soft tissue tumours.

PURPOSE: To identify local and distant complications of patients with soft tissue tumours and evaluate their relationships to types of therapy. METHODS AND MATERIALS: Fifty-one patients (29 males and 22 females, ages 14-80 years) with 34 malignant and 17 benign soft tissue tumours were evaluated for local and distant complications after resection or amputation only (26 patients) or after the addition of radiotherapy (25 patients: 17 patients had external beam therapy, 7 patients had external beam therapy and brachytherapy, and one patient had extracorporeal irradiation and reimplantation). Duration of follow-up averaged 3.75 years for malignant tumours and 2.79 years for benign tumours. Follow-up studies included radiography, T1- and T2-weighted magnetic resonance (MR) imaging, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography for thoracic and abdominal metastases, and 3-phase technetium-99m-labeled-methylene-diphosphonate scintigraphy for bone metastases. RESULTS: Recurrent tumours were 2.2 times more frequent in patients who had undergone their initial resection at an outside hospital as compared with those first treated at the university hospital. Nine of 11 recurrences occurred after marginal surgery. Metastases from soft tissue sarcomas, most commonly to lung (nine patients) and to bone and muscle (five patients), showed no specific relationship to type of therapy. DCE-MRI differentiated rapidly enhancing soft tissue recurrences (11 patients) and residual tumours (6 patients) from slowly enhancing muscle inflammation, and non-enhancing fibrosis and seromas that usually did not enhance. Seromas developed in 76% of patients who had postoperative radiation therapy and in 7.7% of patients who had only surgery. Subcutaneous and cutaneous oedema and muscle inflammation was at least four times more frequent after adjunct radiotherapy than after resection alone. Irrespective of the type of treatment, inflammatory changes in muscle and subcutaneous and cutaneous tissue and the majority of seromas were evident at the first follow-up study. Although seromas after resection and external beam therapy resolved with time, seromas after additional brachytherapy persisted. Inflammatory changes in muscle and cutaneous and subcutaneous tissue after resection alone disappeared by the second follow-up study, whereas these changes after radiotherapy resolved months to years after treatment. Fourteen of 51 patients showed MR findings of chronic muscular atrophy, predominantly located in the lower extremity. Heterotopic ossification was seen in three patients after resection and amputation without radiotherapy. Except for one patient with aggressive fibromatosis, bone and nerve complications occurred in patients with soft tissue malignancy. Twelve patients had osteoporosis. Six patients sustained fractures in irradiated osteoporotic bone of the lower extremity, and one patient had a vertebral fracture in radiographically normal but irradiated bone. In addition, one patient was found to have a medullary infarct in an irradiated femur. In nerve entrapment, DCE-MRI demonstrated the rapidly enhancing recurrent tumour or non-enhancing fibrosis surrounding the slowly enhancing nerve. T1- and T2-weighted MR images displayed the acute and chronic sequelae of nerve entrapment and nerve transection with denervation as T2-hyperintense acute muscle atrophy or T1-hypertense chronic fatty muscular atrophy with decrease in muscle volume. CONCLUSION: This study suggests a possible relationship between types of treatment of soft tissue tumours and subsequent complications. Postoperative radiotherapy was associated with a significant number of patients with seromas, muscle, cutaneous and subcutaneous inflammation, and fractures. Incomplete or difficult surgery resulted in residual or recurrent tumours and heterotopic ossification. Muscle atrophy and nerve entrapment were related to both treatments (resection alone or radiotherapy after resection). Diligent follow-up of patients with soft tissue tumours with recognition of these complications and their differentiation from recurrent or residual tumour can help guide clinical care and may negate the need for surgery when benign disease is defined.