Christopher R. Porter

A nomogram predicting long-term biochemical recurrence after radical prostatectomy

Men who undergo radical prostatectomy (RP) are at long‐term risk of biochemical recurrence (BCR). In this report, the authors have described a model capable of predicting BCR up to at least 15 years after RP that can adjust predictions according to the disease‐free interval.

Active Surveillance Is the Preferred Approach to Clinical Stage I Testicular Cancer

Craig R. Nichols, Virginia Mason Medical Center, Seattle, WA Bruce Roth, Washington University School of Medicine, St Louis, MO Peter Albers, University Hospital Heinrich-Heine, University of Dusseldorf, Dusseldorf, Germany Lawrence H. Einhorn and Richard Foster, Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN Siamak Daneshmand, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA Michael Jewett and Padraig Warde, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada Christopher J. Sweeney and Clair Beard, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA Tom Powles, Bart’s Cancer Institute, St Bartholomew’s Hospital, Queen Mary University of London, London, United Kingdom Scott Tyldesley and Alan So, British Columbia Cancer Agency–Vancouver Cancer Centre, University of British Columbia, Vancouver, British Columbia, Canada Christopher Porter and Semra Olgac, Virginia Mason Medical Center, Seattle, WA Karim Fizazi, Institute Gustave Roussy, University of Paris Sud, Paris, France Brandon Hayes-Lattin, Knight Cancer Institute, Oregon Health and Science University, Portland, OR Peter Grimison, Royal Prince Alfred Hospital, Sydney Cancer Centre, University of Sydney, Sydney, New South Wales, Australia Guy Toner, Peter MacCallum Cancer Center, University of Melbourne, Melbourne, Victoria, Australia Richard Cathomas, Kantonsspital Graubuenden, Chur, Switzerland Carsten Bokemeyer, University Medical Centre Eppendorf, Hamburg University, Hamburg, Germany Christian Kollmannsberger, British Columbia Cancer Agency–Vancouver Cancer Centre, University of British Columbia, Vancouver, British Columbia, Canada

Recent developments in tissue-type imaging (TTI) for planning and monitoring treatment of prostate cancer.

Because current methods of imaging prostate cancer are inadequate, biopsies cannot be effectively guided and treatment cannot be effectively planned and targeted. Therefore, our research is aimed at ultrasonically characterizing cancerous prostate tissue so that we can image it more effectively and thereby provide improved means of detecting, treating and monitoring prostate cancer. We base our characterization methods on spectrum analysis of radiofrequency (rf) echo signals combined with clinical variables such as prostate-specific antigen (PSA). Tissue typing using these parameters is performed by artificial neural networks. We employed and evaluated different approaches to data partitioning into training, validation, and test sets and different neural network configuration options. In this manner, we sought to determine what neural network configuration is optimal for these data and also to assess possible bias that might exist due to correlations among different data entries among the data for a given patient. The classification efficacy of each neural network configuration and data-partitioning method was measured using relative-operating-characteristic (ROC) methods. Neural network classification based on spectral parameters combined with clinical data generally produced ROC-curve areas of 0.80 compared to curve areas of 0.64 for conventional transrectal ultrasound imaging combined with clinical data. We then used the optimal neural network configuration to generate lookup tables that translate local spectral parameter values and global clinical-variable values into pixel values in tissue-type images (TTIs). TTIs continue to show cancerous regions successfully, and may prove to be particularly useful clinically in combination with other ultrasonic and nonultrasonic methods, e.g., magnetic-resonance spectroscopy.

ACR Appropriateness Criteria prostate cancer--pretreatment detection, staging, and surveillance.

Prostate cancer is the most common noncutaneous male malignancy in the United States. The use of serum prostate-specific antigen as a screening tool is complicated by a significant fraction of nonlethal cancers diagnosed by biopsy. Ultrasound is used predominately as a biopsy guidance tool. Combined rectal examination, prostate-specific antigen testing, and histology from ultrasound-guided biopsy provide risk stratification for locally advanced and metastatic disease. Imaging in low-risk patients is unlikely to guide management for patients electing up-front treatment. MRI, CT, and bone scans are appropriate in intermediate-risk to high-risk patients to better assess the extent of disease, guide therapy decisions, and predict outcomes. MRI (particularly with an endorectal coil and multiparametric functional imaging) provides the best imaging for cancer detection and staging. There may be a role for prostate MRI in the context of active surveillance for low-risk patients and in cancer detection for undiagnosed clinically suspected cancer after negative biopsy results. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high‐risk, locally advanced prostate cancer

Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high‐risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP).

Increasing the number of biopsy cores improves the concordance of biopsy Gleason score to prostatectomy Gleason score.

To evaluate taking more biopsy cores for predicting the radical prostatectomy (RP) Gleason score compared with the biopsy Gleason score, as although random sextant biopsies are the standard for a tissue diagnosis of prostate cancer, and taking more biopsies increases the detection rate, it is uncertain whether taking more cores improves the prediction of the RP Gleason score.

Quantitative Ultrasound in Cancer Imaging

Ultrasound is a relatively inexpensive, portable, and versatile imaging modality that has a broad range of clinical uses. It incorporates many imaging modes, such as conventional gray-scale B-mode imaging to display echo amplitude in a scanned plane; M-mode imaging to track motion at a given fixed location over time; duplex, color, and power Doppler imaging to display motion in a scanned plane; harmonic imaging to display nonlinear responses to incident ultrasound; elastographic imaging to display relative tissue stiffness; and contrast-agent imaging with simple contrast agents to display blood-filled spaces or with targeted agents to display specific agent-binding tissue types. These imaging modes have been well described in the scientific, engineering, and clinical literature. A less well-known ultrasonic imaging technology is based on quantitative ultrasound (QUS), which analyzes the distribution of power as a function of frequency in the original received echo signals from tissue and exploits the resulting spectral parameters to characterize and distinguish among tissues. This article discusses the attributes of QUS-based methods for imaging cancers and providing improved means of detecting and assessing tumors. The discussion will include applications to imaging primary prostate cancer and metastatic cancer in lymph nodes to illustrate the methods.

Prognostic value of ERG oncoprotein in prostate cancer recurrence and cause-specific mortality

ETS‐related gene (ERG) protein is present in 40–70% of prostate cancer and is correlated with TMPRSS2‐ERG gene rearrangements. This study evaluated ERG expression at radical prostatectomy to determine whether it was predictive of earlier relapse or prostate cancer‐specific mortality (PCSM).

Incidence of second malignancies after external beam radiotherapy for clinical stage I testicular seminoma.

Study Type – Harm (case series)

PPP2R2C Loss Promotes Castration-Resistance and Is Associated with Increased Prostate Cancer-Specific Mortality

Metastatic prostate cancers generally rely on androgen receptor (AR) signaling for growth and survival, even following systemic androgen-deprivation therapy (ADT). However, recent evidence suggests that some advanced prostate cancers escape ADT by using signaling programs and growth factors that bypass canonical AR ligand-mediated mechanisms. We used an in vitro high-throughput RNA interference (RNAi) screen to identify pathways in androgen-dependent prostate cancer cell lines whose loss-of-function promotes androgen ligand-independent growth. We identified 40 genes where knockdown promoted proliferation of both LNCaP and VCaP prostate cancer cells in the absence of androgen. Of these, 14 were downregulated in primary and metastatic prostate cancer, including two subunits of the protein phosphatase 2 (PP2A) holoenzyme complex: PPP2R1A, a structural subunit with known tumor-suppressor properties in several tumor types; and PPP2R2C, a PP2A substrate-binding regulatory subunit that has not been previously identified as a tumor suppressor. We show that loss of PPP2R2C promotes androgen ligand depletion-resistant prostate cancer growth without altering AR expression or canonical AR-regulated gene expression. Furthermore, cell proliferation induced by PPP2R2C loss was not inhibited by the AR antagonist MDV3100, indicating that PPP2R2C loss may promote growth independently of known AR-mediated transcriptional programs. Immunohistochemical analysis of PPP2R2C protein levels in primary prostate tumors determined that low PPP2R2C expression significantly associated with an increased likelihood of cancer recurrence and cancer-specific mortality. These findings provide insights into mechanisms by which prostate cancers resist AR-pathway suppression and support inhibiting PPP2R2C complexes or the growth pathway(s) activated by PPP2R2C as a therapeutic strategy. Mol Cancer Res; 11(6); 568–78. ©2013 AACR.