Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Assessment of concomitant non-oncologic medication in patients with surgically treated renal cell carcinoma: impact on prognosis, cell-cycle progression and proliferation.

INTRODUCTION: Based on the observation of beneficial effects on cancer metabolism, microenvironment, or VEGF-signaling, several non-anticancer drugs have been discussed as useful in renal cell carcinoma (RCC). In the present study, we investigated the prognostic impact of concomitant medication in RCC and correlated comedication with cell-cycle and proliferation activity in corresponding surgical specimen. METHODS: A total of 388 patients who underwent surgery for localized RCC were included. The individual medication was evaluated according to substance classes. Tissue microarrays from corresponding tumor specimen were immunohistochemically (IHC) stained for Cyclin D1 and Ki67 and semi-quantitatively evaluated. Uni- and multivariate analyses were used to compare survival outcomes. For the comparison of IHC expression according to medication subgroups, Kruskal-Wallis analysis was performed. RESULTS: Median follow-up was 57.93 months (95% CI 53.27-69.43) and median OS accounted for 181.12 months (129.72-237.17). Univariate analysis identified pathological standard variables (T-stage > T2, Grading > G2, L1, N1, M1, sarcomatoid subtype, necrosis) as significant determinants of OS. Moreover, statin use (p = 0.009) and sartan use (p = 0.032) were significantly associated with improved OS. Multivariate analysis identified M1-stage (p < 0.001), statin and sartan use (p = 0.003 and p = 0.033, respectively) as independent prognosticators of survival. Expression of Ki67 was significantly reduced in patients with statin use (p = 0.013), while Cyclin D1 expression showed no correlation with comedication. CONCLUSIONS: Concomitant intake of statins and sartans identifies as an independent predictor of OS in RCC, and reduced Ki67 expression was significantly associated with statin use. Further evaluation of drug repurposing approaches with these substances in RCC appear warranted.

Intention-to-Treat Analysis of 68Ga-PSMA and 11C-Choline PET/CT Versus CT for Prostate Cancer Recurrence After Surgery.

Biochemical recurrence (BCR) after prostate cancer surgery is common, even after additional salvage radiotherapy. BCR might be explained by target miss. Improved diagnostic accuracy provided by PET could potentially circumvent this therapeutic gap. Therefore, we evaluated consecutive 68Ga-prostate-specific membrane antigen (PSMA) PET/CT, 11C-choline PET/CT, and standard CT imaging in the same patient with regard to TNM-stage migration and accordingly adapted curative radiotherapy options including ablative treatment of oligometastases (n ≤ 5). The cost efficacy of PET- versus CT-based treatment was also calculated. Methods: The prospective register database (064/2013BO1) was retrospectively searched for patients fulfilling the following 3 inclusion criteria: BCR after radical prostatectomy (pT2-pT4 pN0-pN1 cM0, postoperative radiotherapy allowed); 11C-choline PET/CT, 68Ga-PSMA PET/CT, and diagnostic CT performed within 24 h; and available clinical data. Ten treatment routines were defined according to current practice. Furthermore, intention-to-treat and treatment-related costs depending on the shift of TNM stage after imaging were analyzed. Eighty-three patients were eligible (median prostate-specific antigen level, 1.9 ng/mL). Results: Both PET examinations led to concordant results in 72% of patients, whereas the concordance of TNM staging between 68Ga-PSMA PET and diagnostic CT was only 36%. Incorrect staging would lead to "wrong" treatment and therefore to additional costs. A 68Ga-PSMA PET study would be cost-effective if additional costs do not exceed €3,844 ($4,312) (vs. CT). The number needed to image was 2 (for CT) and 4 (for 11C-choline PET) to avoid 1 incorrect treatment. In addition, 68Ga-PSMA PET staging enabled new curative options in half the patients with previous radiotherapy who otherwise receive palliative androgen deprivation therapy. Conclusion:68Ga-PSMA PET/CT is cost-effective in all patients with regard to avoidance of incorrect treatment. It enabled new curative options for patients with previous radiotherapy who are usually treated palliatively. Therefore, 68Ga-PSMA PET/CT staging should become standard for BCR after surgery with or without radiotherapy.

Imaging response assessment of immunotherapy in patients with renal cell and urothelial carcinoma.

PURPOSE OF REVIEW: Recent advances in anticancer immunotherapy have revolutionized the treatment of metastatic renal cell (RCC) and urothelial carcinoma. In this review, we discuss the mechanisms of action of these new therapeutic approaches, explicate the common adverse events, and highlight different imaging-based response criteria. RECENT FINDINGS: The recent introduction of immune-checkpoint inhibitors led to substantial advances in therapy of metastatic RCC and urothelial carcinoma. Because of the distinct effector mechanisms of these new substances, atypical response patterns such as transient enlargements of tumor lesions, appearance of new lesions after therapy, no measurable decrease in tumor size, or delayed responses are observed in medical imaging studies. This indicates that the established imaging-based response assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines has shortcomings to comprehensively evaluate treatment effects. SUMMARY: While monitoring response to immunotherapy still relies on RECIST criteria, immune-related response criteria have been established to better address the imaging changes occurring under immunotherapy. Further studies with long-term follow-up are needed to properly identify and predict response after treatment beyond progression. Because of the expanding clinical use of immune checkpoint inhibitors, radiologists, urologist, and oncologists should be familiar with common imaging findings under this respective therapy.

Tumour response in metastatic renal cell carcinoma treated with tyrosine kinase inhibitors - assessment of intra-tumour heterogeneity.

Intra-tumour heterogeneity is a common molecular phenomenon in metastatic clear cell renal carcinoma (mRCC), representing the genetic complexity of a tumour with multiple metastatic sites. The present commentary discusses the observed phenomena of phenotypic intra-tumour heterogeneity in mRCC patients treated with the tyrosine kinase inhibitors sunitinib or pazopanib. Here, drug response can be different on the level of each evaluated metastasis in the individual patient. This questions the currently used radiologic staging systems of RECIST criteria and demands for a modification of radiologic response assessment with the consequence of a patient-tailored therapy in the clinical setting.Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0729-9 .