Phillip M. Pierorazio

To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The Gleason scoring system is a well-established predictor of pathological stage and oncological outcomes for men with prostate cancer. Modifications throughout the last few decades - most recently by the International Society of Urological Pathology (ISUP) in 2005 - have attempted to improve the correlation between biopsy and radical prostatectomy Gleason sum and better stratify patients to predict clinical outcomes. Based on these clinical outcomes and the excellent prognosis for patients with low Gleason scores, we recommend Gleason grades incorporating a prognostic grade grouping which accurately reflect prognosis and are clearly understood by physicians and patients alike. OBJECTIVE: To investigate pathological and short-term outcomes since the most recent Gleason system modifications by the International Society of Urological Pathology (ISUP) in an attempt to divide the current Gleason grading system into prognostically accurate Gleason grade groups. PATIENTS AND METHODS: We queried the Johns Hopkins Radical Prostatectomy Database (1982-2011), approved by the institutional review board, for men undergoing radical prostatectomy (RP) without a tertiary pattern since 2004 and identified 7869 men. Multivariable models were created using preoperative and postoperative variables; prognostic grade group (Gleason grade ≤ 6; 3 + 4; 4 + 3; 8; 9-10) was among the strongest predictors of biochemical recurrence-free (BFS) survival. RESULTS: Significant differences were noted among the Gleason grade groups at biopsy; differences were noted in the race, PSA level, clinical stage, number of positive cores at biopsy and the maximum percentage of positive cores among the Gleason grade groups at RP. With a median (range) follow-up of 2 (1-7) years, 5-year BFS rates for men with Gleason grade ≤ 6, 3 + 4, 4 + 3, 8 and 9-10 tumours at biopsy were 94.6, 82.7, 65.1, 63.1 and 34.5%, respectively (P < 0.001 for trend); and 96.6, 88.1, 69.7, 63.7 and 34.5%, respectively (P < 0.001), based on RP pathology. CONCLUSIONS: The 2005 ISUP modifications to the Gleason grading system for prostate carcinoma accurately categorize patients by pathological findings and short-term biochemical outcomes but, while retaining the essence of the Gleason system, there is a need for a change in its reporting to more closely reflect tumour behaviour. We propose reporting Gleason grades, including prognostic grade groups which accurately reflect prognosis as follows: Gleason score ≤ 6 (prognostic grade group I); Gleason score 3+4=7 (prognostic grade group II); Gleason score 4+3=7 (prognostic grade group III); Gleason score 4+4=8 (prognostic grade group (IV); and Gleason score 9-10 (prognostic grade group (V).

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.

Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.