Intrinsic molecular subtypes may explain marked variation between bladder cancer patients in prognosis and response to therapy. Complex testing algorithms and little attention to more prevalent, early-stage (non-muscle invasive) bladder cancers (NMIBCs) have hindered implementation of subtyping in clinical practice. Here, using a three-antibody immunohistochemistry (IHC) algorithm, we identify the diagnostic and prognostic associations of well-validated proteomic features of basal and luminal subtypes in NMIBC. By IHC, we divided 481 NMIBCs into basal (GATA3 À /KRT5 + ) and luminal (GATA3 + /KRT5 variable) subtypes. We further divided the luminal subtype into URO (p16 low), URO-KRT5 + (KRT5 + ), and genomically unstable (GU) (p16 high) subtypes. Expression thresholds were confirmed using unsupervised hierarchical clustering. Subtypes were correlated with pathology and outcomes. All NMIBC cases clustered into the basal/squamous (basal) or one of the three luminal (URO, URO-KRT5 + , and GU) subtypes. Although uncommon in this NMIBC cohort, basal tumors (3%, n = 16) had dramatically higher grade (100%, n = 16, odds ratio [OR] = 13, relative risk = 3.25) and stage, and rapid progression to muscle invasion (median progression-free survival = 35.4 months, p = 0.0001). URO, the most common subtype (46%, n = 220), showed rapid recurrence (median recurrence-free survival [RFS] = 11.5 months, p = 0.039) compared to its GU counterpart (29%, n = 137, median RFS = 16.9 months), even in patients who received intravesical immunotherapy (p = 0.049). URO-KRT5 + tumors (22%, n = 108) were typically low grade (66%, n = 71, OR = 3.7) and recurred slowly (median RFS = 38.7 months). Therefore, a simple immunohistochemical algorithm can identify clinically relevant molecular subtypes of NMIBC. In routine clinical practice, this three-antibody algorithm may help clarify diagnostic dilemmas and optimize surveillance and treatment strategies for patients.

No abstract

No abstract

Objective: In contrast to traditional views of incurability, patients with oligometastatic disease present with an opportunity for disease eradication with aggressive treatment. There is mounting evidence in investigating the role of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer (OMPC). Methods: MEDLINE and EMBASE were queried for prospective cohort studies reporting the outcomes of metachronous OMPC treated with SBRT. The primary outcome was overall local control. Secondary outcomes included androgen deprivation therapy free survival (ADTFS), biochemical recurrence free survival (BCFS), and progression free survival (PFS). When appropriate, these endpoints were combined in a meta-analysis. Results: We screened 356 abstracts and identified 10studies to include in our analysis, with a total of 653patients and 1111lesions. The maximum number of lesions included in any single study ranged from 3 to 5. PET-CT staging occurred in 92.4% of all patients. SBRT dose varied, with BED1.5 ranging from 152 to 408. Only one Grade three bone toxicity was observed. Meta-analysis reported an overall local control rate of 97% (95% CI, 93–99).Median ADTFSwas24.7 months (95% CI, 20.1–29.2 months). Two-year BCFS, PFS, and ADTFS were 33% (95% CI, 11–55), 39% (95% CI, 24–54), and 52% (95%CI, 41–62) respectively. Patients treated with SBRT were half as likely to experience biochemical recurrence than those on observation when looking at randomized control trial data alone. Conclusion: SBRT appears to be effective in controlling overall disease burden in metachronous OMPC patients and is associated with minimal significant toxicity. The current prospective literature is scarce, and further prospective data is needed to guide treatment recommendations. Advances in knowledge: This study provides a comprehensive summary of prospective evidence reporting the outcomes of SBRT in the management of OMPC patients. We quantify the rates of local control, biochemical free recurrence, progression free survival, and ADT free survival through meta-analysis.

No abstract