Unmet needs in the prediction and detection of metastases in prostate cancer.

The therapeutic landscape for the treatment of advanced prostate cancer is rapidly evolving, especially for those patients with metastatic castration-resistant prostate cancer (CPRC). Despite advances in therapy options, the diagnostic landscape has remained relatively static, with few guidelines or reviews addressing the optimal timing or methodology for the radiographic detection of metastatic disease. Given recent reports indicating a substantial proportion of patients with CRPC thought to be nonmetastatic (M0) are in fact metastatic (M1), there is now a clear opportunity and need for improvement in detection practices. Herein, we discuss the current status of predicting the presence of metastatic disease, with a particular emphasis on the detection of the M0 to M1 transition. In addition, we review current data on newer imaging technologies that are changing the way metastases are detected. Whether earlier detection of metastatic disease will ultimately improve patient outcomes is unknown, but given that the therapeutic options for those with metastatic and nonmetastatic CPRC vary, there are considerable implications of how and when metastases are detected.

[1]  M. Gleave,et al.  Detection of previously unidentified metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic, castration resistant prostate cancer. , 2012, The Journal of urology.

[2]  S. Freedland,et al.  Predictors of metastatic disease in men with biochemical failure following radical prostatectomy. , 2004, The Journal of urology.

[3]  F. Keeley,et al.  Laparoscopic lymph node sampling in locally advanced prostate cancer. , 2002, BJU international.

[4]  C. Tangen,et al.  Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. , 2004, The New England journal of medicine.

[5]  J. Moul,et al.  Biochemical recurrence after definitive prostate cancer therapy. Part I: Defining and localizing biochemical recurrence of prostate cancer* , 2005, Current opinion in urology.

[6]  O. Schober,et al.  Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. , 2001, AJR. American journal of roentgenology.

[7]  S. Hazell,et al.  Use of [11C]Choline PET-CT as a Noninvasive Method for Detecting Pelvic Lymph Node Status from Prostate Cancer and Relationship with Choline Kinase Expression , 2011, Clinical Cancer Research.

[8]  Laurence Collette,et al.  Can whole-body magnetic resonance imaging with diffusion-weighted imaging replace Tc 99m bone scanning and computed tomography for single-step detection of metastases in patients with high-risk prostate cancer? , 2012, European urology.

[9]  B. Tombal,et al.  Modern Detection of Prostate Cancer's Bone Metastasis: Is the Bone Scan Era Over? , 2011, Advances in urology.

[10]  E. Antonarakis,et al.  Changes in PSA kinetics predict metastasis‐free survival in men with PSA‐recurrent prostate cancer treated with nonhormonal agents , 2012, Cancer.

[11]  H. Scher,et al.  Time to Detectable Metastatic Disease in Patients with Rising Prostate-Specific Antigen Values following Surgery or Radiation Therapy , 2005, Clinical Cancer Research.

[12]  Pierre I Karakiewicz,et al.  An updated catalog of prostate cancer predictive tools , 2008, Cancer.

[13]  C. Claussen,et al.  Comparison of 11C-choline-PET/CT and whole body-MRI for staging of prostate cancer , 2006, Nuklearmedizin.

[14]  J Kotzerke,et al.  Intraindividual comparison of [11C]acetate and [11C]choline PET for detection of metastases of prostate cancer , 2003, Nuklearmedizin.

[15]  L. Rybak,et al.  Radiological imaging for the diagnosis of bone metastases. , 2001, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[16]  P. Therasse,et al.  Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Thomas Wiegel,et al.  Guidelines on Prostate Cancer , 2013 .

[18]  N. Spry,et al.  18F-Fluoromethylcholine (FCH) PET imaging in patients with castration-resistant prostate cancer: prospective comparison with standard imaging , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[19]  Maria Triantafyllou,et al.  Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients. , 2009, European urology.

[20]  S. Larson,et al.  89Zr-DFO-J591 for ImmunoPET of Prostate-Specific Membrane Antigen Expression In Vivo , 2010, The Journal of Nuclear Medicine.

[21]  Y. Erdi,et al.  PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[22]  H. Thaler,et al.  Endo-rectal coil magnetic resonance imaging in clinically localized prostate cancer: is it accurate? , 1996, The Journal of urology.

[23]  T. Au-yong,et al.  Comparison of bone single-photon emission tomography and planar imaging in the detection of vertebral metastases in patients with back pain , 1998, European Journal of Nuclear Medicine.

[24]  Stone Nn,et al.  Laparoscopic pelvic lymph node dissection in the staging of prostate cancer , 1999 .

[25]  F. Saad,et al.  Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  R Weissleder,et al.  MR lymphangiography using ultrasmall superparamagnetic iron oxide in patients with primary abdominal and pelvic malignancies: radiographic-pathologic correlation. , 1999, AJR. American journal of roentgenology.

[27]  C. Dence,et al.  Positron tomographic assessment of androgen receptors in prostatic carcinoma , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[28]  Heiko Schöder,et al.  Positron emission tomography for prostate, bladder, and renal cancer. , 2004, Seminars in nuclear medicine.

[29]  A W Partin,et al.  Natural history of progression after PSA elevation following radical prostatectomy. , 1999, JAMA.

[30]  F. Saad,et al.  Abiraterone in metastatic prostate cancer without previous chemotherapy. , 2013, The New England journal of medicine.

[31]  P. Waldenberger,et al.  Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET–CT: a comparative study , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[32]  R. Weissleder,et al.  Detection of lymph node metastases by contrast‐enhanced MRI in an experimental model , 2002, Magnetic resonance in medicine.

[33]  H. Schirrmeister,et al.  Prospective evaluation of the clinical value of planar bone scans, SPECT, and (18)F-labeled NaF PET in newly diagnosed lung cancer. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[34]  B. Trock,et al.  The natural history of metastatic progression in men with prostate‐specific antigen recurrence after radical prostatectomy: long‐term follow‐up , 2012, BJU international.

[35]  P. Kantoff,et al.  Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  U. Metser,et al.  The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[37]  S. Boorjian,et al.  Dynamic prediction of metastases after radical prostatectomy for prostate cancer , 2011, BJU international.

[38]  N. Sanfilippo,et al.  Management of High-Risk Localized Prostate Cancer , 2011, Advances in urology.

[39]  E. Melhem,et al.  A comparison of whole-body turboSTIR MR imaging and planar 99mTc-methylene diphosphonate scintigraphy in the examination of patients with suspected skeletal metastases. , 1997, AJR. American journal of roentgenology.

[40]  J. Moul,et al.  Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. , 2003, Urology.

[41]  M. Kattan,et al.  Pattern of prostate-specific antigen (PSA) failure dictates the probability of a positive bone scan in patients with an increasing PSA after radical prostatectomy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  N F Wasserman,et al.  Preoperative assessment of prostatic carcinoma by computerized tomography. Weaknesses and new perspectives. , 1992, Urology.

[43]  Peter H Gann,et al.  Prostate specific antigen best practice statement: 2009 update. , 2009, The Journal of urology.

[44]  D. Mankoff,et al.  C11-Acetate and F-18 FDG PET for Men With Prostate Cancer Bone Metastases: Relative Findings and Response to Therapy , 2011, Clinical nuclear medicine.

[45]  J. Mohler,et al.  Preoperative prediction of pathological tumor volume and stage in clinically localized prostate cancer: comparison of digital rectal examination, transrectal ultrasonography and magnetic resonance imaging. , 1991, The Journal of urology.

[46]  J. Moul,et al.  Biochemical recurrence after definitive prostate cancer therapy. Part II: Treatment strategies for biochemical recurrence of prostate cancer* , 2005, Current opinion in urology.

[47]  F. Saad,et al.  Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial , 2012, The Lancet.

[48]  F. Saad,et al.  A phase III, randomized study of the investigational agent TAK-700 plus prednisone for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  T. Nozaki,et al.  Usefulness of single photon emission computed tomography imaging in the detection of lumbar vertebral metastases from prostate cancer , 2008, International journal of urology : official journal of the Japanese Urological Association.

[50]  J. Pruim,et al.  Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-choline PET. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[51]  R. Eeles,et al.  Whole‐body magnetic resonance imaging in the detection of skeletal metastases in patients with prostate cancer , 2009, Journal of medical imaging and radiation oncology.

[52]  Y. Erdi,et al.  Tumor Localization of 16β-18F-Fluoro-5α-Dihydrotestosterone Versus 18F-FDG in Patients with Progressive, Metastatic Prostate Cancer , 2004 .

[53]  M. Picchio,et al.  The role of PET/computed tomography scan in the management of prostate cancer , 2011, Current opinion in urology.

[54]  M. Kattan,et al.  Comparisons of nomograms and urologists' predictions in prostate cancer. , 2002, Seminars in urologic oncology.

[55]  A. Jemal,et al.  Cancer statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[56]  E. Antonarakis,et al.  The effect of PSA doubling time (PSADT) and Gleason score on the PSA at the time of initial metastasis in men with biochemical recurrence after prostatectomy. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[57]  E. Antonarakis,et al.  Long‐term overall survival and metastasis‐free survival for men with prostate‐specific antigen‐recurrent prostate cancer after prostatectomy: analysis of the Center for Prostate Disease Research National Database , 2011, BJU international.

[58]  B. Trock,et al.  The natural history of men treated with deferred androgen deprivation therapy in whom metastatic prostate cancer developed following radical prostatectomy. , 2008, The Journal of urology.

[59]  Y. Kuo,et al.  Prevalent and incident use of androgen deprivation therapy among men with prostate cancer in the United States. , 2011, Urologic oncology.

[60]  H. Scher,et al.  Initial phase II experience of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration-resistant prostate cancer (mCRPC). , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  G. Andriole,et al.  The natural history, skeletal complications, and management of bone metastases in patients with prostate carcinoma , 2000, Cancer.

[62]  E. Adang,et al.  The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. , 2008, Clinical radiology.

[63]  Naoto T Ueno,et al.  Bone imaging in metastatic breast cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  Josef Hammer,et al.  The Use of F-18 Choline PET in the Assessment of Bone Metastases in Prostate Cancer: Correlation with Morphological Changes on CT , 2010, Molecular Imaging and Biology.

[65]  Yun Yen,et al.  NCCN clinical practice guidelines in oncology: hepatobiliary cancers. , 2009, Journal of the National Comprehensive Cancer Network : JNCCN.

[66]  J. Carles,et al.  Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). , 2012 .

[67]  G. Cook,et al.  MRI or bone scan or both for staging of prostate cancer? , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  B. Tombal,et al.  Whole-body MRI (WB-MRI) versus axial skeleton MRI (AS-MRI) to detect and measure bone metastases in prostate cancer (PCa) , 2010, European Radiology.

[69]  I. Tannock,et al.  Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. , 2004, The New England journal of medicine.

[70]  J. Nelson,et al.  Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration‐resistant nonmetastatic prostate cancer , 2011, Cancer.

[71]  Kazutaka Saito,et al.  Development, validation, and head-to-head comparison of logistic regression-based nomograms and artificial neural network models predicting prostate cancer on initial extended biopsy. , 2008, European urology.

[72]  A. Partin,et al.  The importance of pelvic lymph node dissection in men with clinically localized prostate cancer. , 2006, Reviews in urology.

[73]  P. Walsh,et al.  Prostate specific antigen at the initial diagnosis of metastasis to bone in patients after radical prostatectomy. , 2010, The Journal of urology.

[74]  M. Poupon,et al.  Multicenter randomized phase II study of two schedules of docetaxel, estramustine, and prednisone versus mitoxantrone plus prednisone in patients with metastatic hormone-refractory prostate cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[75]  F. Saad,et al.  Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone‐refractory prostate cancer , 2008, Cancer.

[76]  Ralph Weissleder,et al.  Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. , 2003, The New England journal of medicine.

[77]  A. Haese*,et al.  Validation of a nomogram for prediction of side specific extracapsular extension at radical prostatectomy. , 2006, The Journal of urology.

[78]  M. Langer,et al.  Diagnostic value of MRI in comparison to scintigraphy, PET, MS-CT and PET/CT for the detection of metastases of bone. , 2005, European journal of radiology.

[79]  V. Vigorita,et al.  Localization of technetium‐99m methylene diphosphonate in bone using microautoradiography , 1986, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.