How many cores are enough? Optimizing the transperineal prostate biopsy template.

INTRODUCTION AND OBJECTIVE: Most urologists use a 10-12 core template during transrectal ultrasound guided prostate biopsy (TRUS-B). A similar consensus template does not exist for transperineal prostate biopsy (TP-B) including the optimal number and location of biopsy cores. We examined our institutional cohort to develop an optimal systematic template for TP-B. METHODS: We prospectively monitored our first 200 consecutive free-hand TP-B. These included men who were biopsy naïve (n = 117), had elevated PSA with prior negative biopsy (n = 18), and men on active surveillance (n = 65). All men underwent a 20 core TP-B with each core placed in a separate specimen container. This allowed the 20-core TP-B to be easily broken down as though fewer cores had been taken in each patient. Ten, 12, and 16 core templates were designed a priori and compared within each patient to the 20 core template. The highest Grade Group (GG) at pathologic analysis was assigned to each biopsy. Primary outcome was detection of clinically significant prostate cancer, defined as ≥GG2. Secondary outcome was detection of GG1 prostate cancer. We performed sub-group analyses of biopsy naïve men and biopsy naïve men stratified by PSA density (<0.15 vs. ≥0.15 ng/mL/cc). An historic institutional cohort of 10-12 core TRUS-B (n = 170) was used to compare prostate cancer detection between techniques. P value of ≤0.05 was considered statistically significant. RESULTS: Clinically significant cancers were detected in 98 men (49%) using a 20 core TP-B technique. Had we sampled fewer cores we would have identified clinically significant cancers in 93 (47%, 16 core), 91 (46%, 12 core), and 82 (41%, 10 core) men. More clinically significant cancers were detected by the 20 core template compared to the 10 core template for both the whole cohort (49% vs. 41%, P = 0.02) and the biopsy naïve subset (48% vs. 40%, P = 0.05). Additional cores did not result in an increased detection of GG1 cancers (20-core: 35% vs. 10-core: 44%, P = 0.09). Less than one quarter of biopsy naïve men with a PSA density <0.15 were found to have clinically significant cancers. More clinically significant cancers were detected in the 12-core TP-B cohort compared to the 12-core TRUS-B series (46% vs. 38%, P < 0.001). CONCLUSIONS: A 20 core TP-B systematic biopsy template detected a greater number of clinically significant prostate cancers compared to a 10 core TP template. Cancer detection was similar for 12, 16, and 20 core templates. Higher core numbers did not result in greater detection of GG1 tumors reflecting increased detection of concomitant ≥GG2 with greater sampling. We propose a minimum 12 core systematic biopsy template for men undergoing TP-B.

Reversion analysis reveals the in vivo immunogenicity of a poorly MHC I-binding cancer neoepitope.

High-affinity MHC I-peptide interactions are considered essential for immunogenicity. However, some neo-epitopes with low affinity for MHC I have been reported to elicit CD8 T cell dependent tumor rejection in immunization-challenge studies. Here we show in a mouse model that a neo-epitope that poorly binds to MHC I is able to enhance the immunogenicity of a tumor in the absence of immunization. Fibrosarcoma cells with a naturally occurring mutation are edited to their wild type counterpart; the mutation is then re-introduced in order to obtain a cell line that is genetically identical to the wild type except for the neo-epitope-encoding mutation. Upon transplantation into syngeneic mice, all three cell lines form tumors that are infiltrated with activated T cells. However, lymphocytes from the two tumors that harbor the mutation show significantly stronger transcriptional signatures of cytotoxicity and TCR engagement, and induce greater breadth of TCR reactivity than those of the wild type tumors. Structural modeling of the neo-epitope peptide/MHC I pairs suggests increased hydrophobicity of the neo-epitope surface, consistent with higher TCR reactivity. These results confirm the in vivo immunogenicity of low affinity or 'non-binding' epitopes that do not follow the canonical concept of MHC I-peptide recognition.