Wednesday, May 30, 2012

Imaging in Prostate Carcinoma 5- Nuclear Imaging

Radionuclide bone scanning after the injection of a technetium-99m (99m Tc) tracer is the standard method for assessing potential bone metastases from prostate cancer. With diffuse bone metastases, a "superscan" may be seen; this superscan demonstrates high uptake throughout the skeleton, with poor or absent renal excretion of the tracer. Evidence-based guidelines for the use of radionuclide bone scans in patients with serum PSA levels greater than 10ng/mL have been devised.
Bone scans have a high sensitivity but low specificity for metastatic prostate cancer. Isotopic bone scans revealing metastatic prostate cancer are shown below.
Isotopic bone scans show multiple areas of increased tracer activity from metastatic prostate cancer.
Isotopic bone scans. Diffuse metastases demonstrate a superscan appearance. Note that no renal excretion of radioactive tracer is demonstrated.

Positron emission tomography (PET) scanning with fluorodeoxyglucose (FDG) may have a role in the detection of lymph node metastases from prostate cancer, particularly in patients with relapsed disease after primary treatment. Localized disease within the prostate and pelvic lymph nodes can be difficult to image because of the proximity of bladder activity. Currently, the sensitivity of FDG-PET for detection of recurrence after radical prostatectomy is less than 50%.
Carbon-11 (11 C) acetate and 11 C choline have shown promise as alternatives to FDG in prostate cancer, but they are still under assessment and are less readily available than FDG. Retrospective image fusion of11 C-acetate PET scanning with CT scanning and MRI is technically feasible and appears to be a promising technique.
The use of immunoscintigraphy to assess prostate cancer is under investigation. This method uses radiotracer-labeled antibodies to acid phosphatase and to PSA. Initial studies used iodine-131–labeled antiprostatic acid phosphatase antibody, and subsequent studies have used indium-111 (111 In )–labeled antibody. The use of labeled anticarcinoembryonic antigen (anti-CEA) antibodies is being investigated.
The most commonly used monoclonal antibody (mAb) is capromab pendetide (ProstaScint; Cytogen, Princeton, NJ), which is indium-111 (111 In)–labeled mAb 7E11-C5.3 (CYT-356, which recognizes an intracellular epitope of prostate-specific membrane antigen [PSMA]). This immunoscintigraphic technique is approved for imaging soft-tissue metastases from prostate cancer but not for bone metastases.

Degree of confidence

FDG-PET has a reported sensitivity of approximately 50% for the detection of skeletal prostatic metastases. In general, FDG-PET has an excellent detection rate for lytic skeletal metastases, but it has a poor detection rate for sclerotic metastases. Disease that localizes within the prostate and pelvic lymph nodes can be difficult to image because of the proximity of bladder activity. The sensitivity of FDG-PET for detecting disease recurrence after radical prostatectomy is currently less than 50%.11 C-acetate and11 C-choline imaging have shown promise as alternatives to FDG-PET imaging in prostate cancer, but these are less readily available than FDG-PET techniques.
In a review of 631 scans, the sensitivity and specificity of capromab pendetide for lymph node metastases were 62% and 72%, respectively; for prostatic fossa recurrence, they were 49% and 71%, respectively. Two roles of capromab pendetide imaging may be advocated: evaluation of newly diagnosed high-grade prostate cancer before definitive treatment and assessment of men with rising PSA levels after definitive treatment (radiotherapy or radical surgery). The fusion of capromab pendetide images with CT or MRI scans can provide details of prostate cancer localization and improve the low spatial resolution of the capromab pendetide images.

False positives/negatives

False-positive bone scan findings may be the result of increased uptake on bone scans not caused by a skeletal abnormality. Artifacts may result from the presence of tracer at the injection site, scars from recent operations, and sweat in the axillae. Physiologic variants that cause false-positive findings may include calcification of cartilage, an inferior angle of the scapula, and bladder diverticulum. Increased tracer uptake on bone scan may be demonstrated as a result of metastatic disease, joint disease, fracture, Paget disease, osteomyelitis, or surgery.

Imaging in Prostate Carcinoma 4- Ultrasonography

Transrectal ultrasonography (TRUS), shown in the images below, plays a central role in the contemporary diagnosis of prostate cancer because it enables accurate, image-guided biopsy of the gland. Patients are usually referred for TRUS because an abnormality is found during DRE or because the serum PSA level is elevated.
Axial transrectal ultrasonographic (TRUS) scan shows extensive hypoechoic area (arrows) in the right peripheral zone. Biopsy revealed prostatic adenocarcinoma.
Axial transrectal ultrasonographic (TRUS) scan shows a hypoechoic area in left peripheral zone and a small hypoechoic area in right peripheral zone (arrows). Biopsy revealed an adenocarcinoma (Gleason grade 6).
Axial transrectal sonogram in a patient with normal results during digital rectal examination and a prostate-specific antigen (PSA) level of 9ng/mL. Image shows extensive bilateral, but predominantly left-sided, hypoechoic areas in the peripheral zone (arrows). Biopsy confirmed a Gleason grade 8 prostate cancer. Minor capsular irregularity is present on the left; this is consistent with a T3 tumor.
Axial transrectal ultrasonographic (TRUS) power Doppler scan in the same patient as in previous image. The patient had normal results with digital rectal examination and a prostate-specific antigen (PSA) level of 9ng/mL. A generalized increase in vascularity was noted in the posterior aspect of the prostate (arrows). However, this finding is not specific to the hypoechoic area in the left peripheral zone, illustrating the difficulty of using Doppler techniques in the assessment of prostate cancer.
Axial transrectal ultrasonographic (TRUS) scan in a patient with clinical benign prostatic hyperplasia (BPH) and a serum prostate-specific antigen (PSA) level of 11ng/mL. Enlargement of the transition zone is present, but no focal abnormality is observed in the peripheral zone. Systematic, 6-core biopsy revealed adenocarcinoma from both lobes of the prostate (ie, this is an isoechoic tumor in the peripheral zone of both prostatic lobes).

TRUS is widely available, well tolerated by patients, and relatively inexpensive. It currently offers the best opportunity to demonstrate a prostate cancer, but because many prostatic tumors are both isoechoic and multifocal, TRUS has major limitations in fully demonstrating prostate cancers. Furthermore, TRUS has a low specificity because many pathologic conditions may appear as similarly hypoechoic areas in the PZ of the prostate. For this reason, diagnostic assessment of cancer in the prostate must be made by means of histologic interpretation of biopsy samples. TRUS provides the opportunity for accurate and comprehensive biopsy of the prostate gland while providing an imaging examination.
Many pathologic processes can appear as a hypoechoic area in the PZ of the prostate or as a hypervascular area on color or power Doppler sonograms. The differential diagnoses of a hypoechoic area in the PZ include prostatitis, tuberculous prostatitis, granulomatous prostatitis, PIN, and prostatic atrophy and infarction. These are accurately differentiated only by using biopsy of the focal ultrasonographic abnormality. Furthermore, because many prostate cancers are isoechoic, these can be identified only by using systematic biopsy techniques.

Imaging findings

With TRUS, the prostate is shown to be divided into an outer gland (PZ and CZ) and an inner gland (TZ). Calcification in the corpora amylacea in the surgical capsule between the outer and inner parts of the prostate is common. Particular attention should be paid to the PZ in prostate cancer diagnosis. The most frequently noted abnormality caused by prostate cancer is a hypoechoic area in the PZ. Rarely, cancer may appear as a hyperechoic area.
Prostate cancer and prostatitis each may have increased vascularity, as shown on color and power Doppler sonograms. This focal alteration in the prostatic vasculature is most commonly found in hypoechoic areas in the PZ, as depicted on gray-scale images. No cancer-specific flow pattern has been identified, and some cancers that are demonstrated clearly on gray-scale Doppler imaging show no focal hypervascularity.
Lymphoma of the prostate tends to present in younger men, and large hypoechoic masses in the TZ and PZ have been reported.
Prostate cancers frequently demonstrate isoechoic findings. This observation is the basis for the systematic biopsy approach in which multiple cores are taken from both lobes in a standardized manner. Color and power Doppler study results have been disappointing, and they have not been significantly helpful in detecting cancers that are isoechoic on gray-scale examination.
Few reports in the published literature describe the detailed sonographic appearances of the rarer histologic variants of prostate cancer. In comedocarcinoma—the most malignant form of prostate cancer—stippled, multiple, small, hyperechoic foci within the hypoechoic area of the cancer have been reported. In one study, multiple small cysts in the prostate were identified in 2 patients with adenoid cystic carcinoma of the prostate.


TRUS may be used for local staging of prostate cancer because it can demonstrate bulges of the prostate capsular outline or overt extracapsular extension. TRUS findings have been found to be inaccurate in the staging of localized prostate cancer, but PZ tumors longer than 2.3cm that contact the fibromuscular rim surrounding the prostate may be associated with extracapsular invasion.

TRUS-guided biopsy

The original systematic approach to biopsy included the acquisition of 6 cores, with 1 core taken bilaterally from each of the prostate lobes at the base, mid-gland, and apex in a parasagittal plane (ie, a "sextant" biopsy). Current practice is to obtain an increased number of cores (ie, lateral PZ cores, midgland cores, or TZ cores) in addition to the standard 6 cores. A 10-core biopsy that incorporates the traditional 6 parasagittal samples plus 2 lateral samples from the right and left prostatic lobes is now a standard technique for systematic biopsy.
Systematic biopsy may be supplemented with cores obtained through hypoechoic PZ lesions. Focal areas of hypervascularity in the PZ of the isoechoic prostate, as shown on color Doppler examination, may also be targeted.
Opinions differ regarding whether TZ cores should be routinely obtained during an initial biopsy procedure or whether the samples may be obtained during repeat biopsy in a patient with an elevated PSA level after the initial systematic biopsy results are negative for malignancy.
Most TZ cancers are found by analyzing systematic biopsy cores specifically obtained from the TZ. Little attention has been paid to assessing hypoechoic areas in the TZ, because of the lower frequency of cancer in the TZ and the perceived lower potential for metastatic spread of primarily TZ cancer. No specific studies in the literature report the biopsy results in focal TZ hypoechoic areas or in areas of specific focal alterations of TZ vascularity, as identified by use of color or power Doppler imaging.
Some authors describe a saturation biopsy approach in which as many as 40 cores are obtained under general anesthesia or sedation. The precise biopsy approach must be individually tailored on the basis of the patient's clinical features (eg, DRE and PSA levels).

Future perspectives

Currently, research studies are under way to investigate whether ultrasonographic contrast agents have a role in the identification of cancer in the prostate and whether, by demonstrating tumor vascularity, they have a role in establishing prognosis of a patient with biopsy-detected prostate cancer.
However, the use of ultrasonographic contrast agents increases the time and cost of ultrasonography-guided prostate biopsy procedures. No marked improvement has been found in the accuracy of prostate cancer diagnosis with contrast agents. These agents remain experimental, and they have not been adopted into standard uroradiologic practice.
Nonetheless, the impact of ultrasonographic contrast agents on radiologic practice could be considerable if future research proves that they enable the quantitative preoperative assessment of microvascular density or that they provide prognostic information in an individual patient.
Research studies are also being conducted to assess the value of elastography in the diagnosis of prostate cancer; however, the role of this technique is still unclear.
In other research, Onik et al found that 3-D prostate mapping biopsy (3-D–PMB; carried out transperineally using a brachytherapy grid under TRUS guidance) can safely and accurately stage prostate cancer patients. The investigators compared 3-D–PMB with traditional TRUS biopsy in 180 patients with unilateral prostate cancer on TRUS biopsy. A median of 50 cores were obtained with 3-D–PMB. In 110 patients (61.1%), biopsies were positive bilaterally, and in 41 patients (22.7%), Gleason scores were increased to 7 or higher.

Imaging in Prostate Carcinoma 3- Magnetic Resonance Imaging

MRI can demonstrate the internal anatomy of the prostate and help clinicians to identify areas of altered signal intensity, which represent focal pathology in the gland. This modality can be used to provide the most complete evaluation of patients with prostate cancer because it can be used to assess primary disease in the prostate, as well as any involvement of the local lymph nodes. Although MRI is used primarily for staging, the availability of interventional MRI units means that MRI is likely to have a future role in the diagnosis of prostate cancer. Images of prostate cancer on MRI are provided below.

Coronal, T2-weighted magnetic resonance imaging (MRI) study of the prostate gland obtained by using an external coil. Low signal intensity (arrow) is seen on the left side of the prostate at the site of a biopsy-proven prostate cancer.

Endorectal, axial, T2-weighted magnetic resonance imaging (MRI) scan in a patient with a prostate-specific antigen level of 8ng/mL and right-sided prostate cancer. Low signal intensity is demonstrated in the right peripheral zone (arrow).

Patient with biopsy-proven prostate cancer. Axial, T1-weighted magnetic resonance imaging (MRI) scan of the pelvis shows an enlarged left obturator node (arrow).

On T1-weighted images, the prostate appears homogeneous with medium signal intensity; neither the zonal anatomy nor intraprostatic pathology is displayed. However, zonal anatomy and intraprostatic pathology are depicted on T2-weighted images, in which the cancer appears as an area of low signal intensity in the hyperintense PZ. The specificity of this appearance is low.
As with TRUS, MRI cannot accurately depict cancer in the TZ. In addition, cancer assessment with MRI may be complicated by post biopsy hemorrhage; therefore, MRI should not be performed until at least 3 weeks after biopsy.
The current role of MRI is the assessment of local extracapsular extension and invasion of the seminal vesicle. Signs of extracapsular spread include the following: irregular bulging of the prostatic outline (see the image below), breach of the capsule with extracapsular spread, asymmetry of the neurovascular bundles, and loss of the rectoprostatic angle.
Endorectal magnetic resonance imaging (MRI) scan in a patient with extensive prostate carcinoma. Image shows a bulge in the capsular outline on the right side (arrow). This is a stage T3 tumor.

Contiguous areas of low signal intensity extending into the seminal vesicles from the base of the prostate are evidence of invasion of the seminal vesicle. On T2-weighted images, reduced signal intensity in the seminal vesicles may be seen after radiation therapy or prostatic biopsy.
The optimal MRI technique for the staging of prostate cancer has not been established. Endorectal MRI appears more accurate than body-coil MRI in the local staging of the primary tumor, and 3Tesla (3T) MR scanners give improved image quality on T2-weighted sequences compared with 1.5T systems.

Diffusion-weighted and contrast-enhanced imaging

Dynamic endorectal MRI with gadolinium enhancement may provide optimal visualization of cancer in the prostate. MR spectroscopy performed with citrate and choline can provide specific information regarding prostatic metabolism; these data may be useful in assessing the biologic potential of the primary tumor and the extracapsular extension of the tumor. New approaches with diffusion-weighted imaging (DWI) sequences and dynamic contrast-enhanced (DCE) MRI sequences are currently under evaluation on 3T and 1.5T scanners in research centers.
DWI and DCE MRI are technically feasible in the prostate. Investigators have studied the potential of DWI with endorectal or phased array coils for the identification and staging of cancer within the prostate. Prostate cancer tissue has a higher cellular density than normal prostate PZ tissue, and this decreases the value of the apparent diffusion coefficient (ADC) on diffusion sequences when compared with normal prostate tissue.
DWI in the prostate suffers from poor spatial resolution compared with T2-weighted images but may be useful as a supplementary technique in drawing attention to areas of suspicion at 1.5T and 3T.
Contrast-enhanced MRI may be used as a complementary technique to T2 imaging; some studies have suggested that it is superior to T2-weighted MR for prostate cancer localization. Technical issues related to the use of contrast-enhanced MRI remain to be clarified and standardized.
Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after they were given a gadolinium-based contrast agent to enhance MRI or MR angiography (MRA) scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

Nodal staging

Nodal staging relies on assessment of lymph node size, and neither CT scanning nor MRI can demonstrate cancer within lymph nodes that are not enlarged. However, a technique to detect clinically occult lymph node metastases using MR lymphography with a highly lymphotropic MR contrast agent was reported.[13]Intravenous lymphotropic paramagnetic nanoparticles of iron oxide, ferumoxtran-10 (Combidex; Advanced Magnetics, Cambridge, MA), were administered, and patients were examined using MRI 24 hours after contrast administration. Small lymph node metastases were identified with higher sensitivity than with conventional MRI.

3-D versus 2-D imaging

Rosenkrantz et al compared 3-dimensional (3-D), T2-weighted imaging sequences with conventional multiplanar, 2-D, turbo spin-echo, T2-weighted sequences for prostate cancer detection, staging, and image quality in 38 men with prostate cancer and found that 3-D, T2-weighted SPACE (sampling perfection with application optimized contrasts sequence with different flip angle evolutions) MRI provided a time saving of about 8 minutes, had similar image quality and accuracy in diagnosing tumors and extracapsular extension, and had better tumor conspicuity.
Images that were obtained with 2-D, turbo spin-echo sequences had a higher signal-to-noise ratio (SNR) for normal peripheral zones, but the SPACE images had greater tumor-to-peripheral zone contrast.

Degree of confidence

Extracapsular extension of a prostatic cancer is usually diagnosed with some certainty. A more difficult assessment is the interpretation of subtle bulges of the capsular outline. A significant number of prostatic cancers may be understaged, even when endorectal MRI is used.
Previous studies have shown that DRE and imaging techniques cause the understaging of cancer localized within the prostate. The most accurate imaging technique for staging prostate cancer appears to be endorectal MRI, but even this may cause significant understaging in approximately 30% of prostate cancers.

Imaging in Prostate Carcinoma 2- Computed Tomography

Arterial-phase, multisection CT scanning can help to differentiate between prostate PZ and prostate TZ regions, but it cannot demonstrate intraprostatic pathology. However, it may be helpful in detecting lymph node involvement.[6]
CT and MRI scans depict lymph node enlargement and have similar accuracy for the evaluation of lymph node metastases. However, nodal staging relies on assessment of lymph node size, and neither CT scan nor MRI can demonstrate cancer within lymph nodes that are not enlarged.
CT scanning can also be used to stage the primary tumor, by depicting extracapsular spread in patients in whom advanced disease is suspected, particularly when radiation therapy is planned.
CT scan studies cannot depict T1 or T2 tumors accurately, but invasion of periprostatic fat or seminal vesicles by T3 tumors may be demonstrated.
Evidence-based guidelines for the use of CT scanning in prostate cancer staging have been produced. CT scanning may also be used to depict soft-tissue metastases elsewhere in the body. The CT scans below depict metastatic prostate cancer.
Axial computed tomography (CT) scan at the level of the kidneys shows extensive para-aortic lymphadenopathy (arrows), which results from advanced prostate cancer.
Metastatic prostate cancer (arrows) involves the soft tissues at the right side of the skull base. The patient presented with right-sided cranial nerve–XII palsy.

Degree of confidence

Previous studies have shown that digital rectal examination (DRE) and imaging techniques cause the understaging of cancer localized within the prostate. The most accurate imaging technique for staging prostate cancer appears to be endorectal MRI, but even this may cause significant understaging in approximately 30% of prostate cancers.
Because staging with CT scanning is performed by assessing the outline of the prostate, there should be little diagnostic confusion if an overt capsular breach is apparent. However, cancer is understaged by using CT scanning because the scans may fail to demonstrate microscopic spread through the prostatic capsule. This spread may be particularly difficult to assess at the apex and base of the prostate.

Imaging in Prostate Carcinoma 1- Radiography

A chest radiograph may be used in the evaluation of a patient with known prostate cancer to assess chest symptoms, weight loss, localized bone pain, or constitutional symptoms. Skeletal radiographs may show sclerotic metastases or lytic lesions with bone destruction. The image below depicts prostate cancer metastases on radiography.
Pelvic radiograph shows widespread, osteoblastic, sclerotic metastases from prostate cancer.
Plain radiographs of the pelvis cannot be used to demonstrate localized disease in the prostate. A radionuclide bone scan is more sensitive than a radiograph for depicting skeletal metastases: bone scans may demonstrate an area of abnormal tracer activity even if the plain radiographic findings are normal.

Enzalutamide Is a 'Game Changer' in Prostate Cancer

May 25, 2012 (Atlanta) — A first-in-class drug, the androgen-receptor signaling inhibitor enzalutamide (MDV3100), has shown a survival benefit in men with post docetaxel prostate cancer. The risk for death decreased by 37% relative to placebo, extending survival by more than 4 months, according to findings from the phase 3 AFFIRM study.
According to the researchers, enzalutamide, an oral hormonal agent, competitively inhibits the binding of androgens to the androgen receptor. It also inhibits androgen receptor nuclear translocation and the association of the receptor with DNA. Enzalutamide displayed activity during phase 1 and 2 trials in pre- and post-chemotherapy patients with progressive castration-resistant prostate cancer.
This is a game-changing agent.
Trials in earlier-stage disease with this agent are ongoing. One large multicenter trial will evaluate this agent in patients who have not received docetaxel. There are also plans to evaluate it in M0 castrate-resistant prostate cancer and in the androgen-sensitive disease state, Dr. Shore said.
"This is a game-changing agent because of its tolerability and, more important, its efficacy and ease of administration," he said. "I think this is an exceptionally optimistic and exciting time for both clinicians and patients."

American Urological Association (AUA) 2012 Annual Scientific Meeting

Wednesday, May 23, 2012

Late-Breaking Science Forum

The following research will be presented during the Late Breaking Science Forum:
  • MDV3100, an Androgen Receptor Signaling Inhibitor, Improves Overall Survival in Men with Post-Docetaxel Prostate Cancer: Baseline Characteristics and Results From the Phase 3 AFFIRM Study, presented by Neil Shore from Myrtle Beach, South Carolina (Abstract LBA1)
  • Serum Glutamate Levels Are Associated With Primary Prostate Cancer Aggressiveness, presented by Shahriar Koochekpour from Buffalo, New York (Abstract LBA2)
  • A Panel of Hub Genes Associated With Aggressiveness and Biochemical Recurrence After Radical Prostatectomy Are More Highly Expressed Among African American Than European American Men, presented by Isaac Powell from Detroit, Michigan (Abstract LBA3)
  • Don't Ask/Don't Tell: Implications of Following Proposed United States Public Health Services (USPHSTF) Recommendations Against Discussing Prostate Cancer Screening, presented by E. David Crawford from Aurora, Colorado (Abstract LBA4)
  • Circulating microRNA Signatures: A Novel Minimally Invasive Biomarker for Prostate Cancer, presented by Brian Kelly from Galway, Ireland (Abstract LBA5)
  • Clinical Utility of a Multiplexed Epigenetic Gene Assay to Detect Cancer in Histopathologically Negative Prostate Biopsies: Results of the Multicenter MATLOC Study, presented by Grant Stewart from Edinburgh, United Kingdom (Abstract LBA6)
  • Nitric Oxide-Releasing Polymeric Microspheres as a Therapy for Erectile Dysfunction, presented by Samit Soni from Houston, Texas (Abstract LBA7)
  • Efficacy and Safety of Avanafil, A Next-Generation, Phosphodiesterase Type 5 Inhibitor for the Treatment of Men With Erectile Dysfunction: Data From Phase 2 and 3 Studies in Difficult-to-Treat Populations, presented by John P. Mulhall from New York City (Abstract LBA8)
  • Autologous Muscle Derived Cells for Treatment of Stress Urinary Incontinence: Dose Escalation Study of Safety and Potential Effectiveness, presented by Kenneth Peters from Royal Oak, Michigan (Abstract LBA9)

Microscopic Hematuria Not Predictive of Cancer

"These data suggest that patients under age 50 with no history of gross hematuria (approximately one third of patients evaluated) may safely avoid unnecessary and potentially hazardous testing for asymptomatic microscopic hematuria," Dr. Loo and colleagues conclude in their abstract. "Microscopic hematuria of any degree should not be used to determine diagnostic evaluation," they add.
The study was not commercially funded. Dr. Loo has disclosed no relevant financial relationships.
American Urological Association (AUA) 2012 Annual Scientific Meeting: Abstract 62. Presented May 19, 2012.

Urethroplasty Outcomes Just as Good in Outpatient Setting

"Outpatient urethroplasty is feasible in most patients; our outcomes are similar to the traditional inpatient approach," the authors conclude in their abstract.
The study was not commercially funded. Dr. Nikolavsky has disclosed no relevant financial relationships.
American Urological Association (AUA) 2012 Annual Scientific Meeting: Abstract 16. Presented May 19, 2012.

Adrenalectomy Plus Nephrectomy Linked to Reduced Survival

"We demonstrate a significant association between performing ipsilateral adrenalectomy and overall survival," Dr. Yap and colleagues conclude in their abstract. "Our findings further support the importance of adrenal-sparing approaches at the time of renal nephrectomy."
The study was not commercially funded. Dr. Yap has disclosed no relevant financial relationships.
American Urological Association (AUA) 2012 Annual Scientific Meeting: Abstract 52. Presented May 19, 2012.

Radium-223 Prolongs Survival in CRPC

May 21, 2012 (Atlanta, Georgia) — In patients with bone metastases and castration-resistant prostate cancer (CRPC), radium-223 chloride (Ra-223) significantly prolonged overall survival and delayed time to first skeletal-related event (SRE), according to new findings from a phase 3 study.
Oliver Sartor, MD, from the Departments of Medicine and Urology at Tulane University School of Medicine in New Orleans, Louisiana, and colleagues presented the findings here in an oral podium session at the American Urological Association (AUA) 2012 Annual Scientific Meeting.
Dr. Sartor noted that Ra-223 is a first-in-class alpha-pharmaceutical that targets bone metastases. ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer), a phase 3, double-blind, randomized, multinational study, compared best standard of care plus Ra-223 or placebo in patients with bone metastases in CRPC.
"This is the first presentation of ALSYMPCA to the urologic community," Dr. Sartor told Medscape Medical News. "The data are roughly comparable in overall survival benefit to the other newer agents, but the toxicity profile appears excellent, and I personally envision that combinations of these newer agents will eventually be used," he said.
In the current study, patients had progressive, symptomatic CRPC with 2 or more bone metastases on scintigraphy and no known visceral metastases. All were receiving best standard of care and had previously received docetaxel, were docetaxel ineligible, or declined to receive docetaxel. Patients were randomly assigned 2:1 to receive 6 injections of Ra-223 every 4 weeks or matching placebo.
Of 924 patients, 615 were randomly assigned to Ra-223 and 307 were assigned to placebo between June 2008 and February 2011. On the basis of data from a planned interim analysis including 809 patients, Ra-223 significantly improved overall survival vs placebo (median overall survival duration, 14.0 vs 11.2 months, respectively; 2-sided P = .00185; hazard ratio [HR], 0.695; 95% confidence interval [CI], 0.552 - 0.875).
Time to first SRE was significantly delayed in the Ra-223 vs the placebo group (median time to SRE, 13.6 vs 8.4 months, respectively; P = .00046; HR, 0.610; 95% CI, 0.461 - 0.807).
Safety and tolerability of Ra-223 were favorable, with 1.8% and 0.8% of patients reporting grade 3/4 neutropenia and 4% and 2% of patients reporting thrombocytopenia in the Ra-223 and placebo groups, respectively. The percentage of patients reporting adverse events was lower in the Ra-223 group than the placebo group (adverse events of any grade in 88% vs 94% and grade 3/4 adverse events in 51% vs 59%, respectively).
"I think two things were surprising," Dr. Sartor said after his presentation. "One is that you have overall survival-positive [attitudes] — everyone moves into these types of trials with a sense of optimism, but until the data is there, you don't know. The other thing that was very nice to see was the lack of toxicity. There was a lot of concern about bone myelosuppression, but the truth is, we just didn't see it."
According to Dr. Sartor, an updated survival analysis will be presented at the upcoming American Society of Clinical Oncology (ASCO) annual meeting.
Session moderator Sam Chang, MD, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, noted that as a bone-targeted agent, this product is "unique in improving overall survival, which would make it a very important option and perhaps game changing."
However, Dr. Chang told Medscape Medical News that these results are demonstrated in a very select population. "This product targets bone turnover, and so those lesions that are most active are the ones most likely to be targeted — the problem is that we don't know when that highest level of activity is," he said. "Also, the study was in a very select population of patients, and at a very late stage. Can it be used earlier on? We don't know."
The study was supported by Algeta. Dr. Sartor reports that he is a consultant and investigator for Algeta and Bayer. Dr. Chang has disclosed no relevant financial relationships.
American Urological Association (AUA) 2012 Annual Scientific Meeting: Abstract #684. Presented May 20, 2012.

Final USPSTF Guidelines: No to Routine PSA Testing

"The USPSTF concludes that there is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.

Testosterone Okay After Radical Prostatectomy

A statistically but not clinically significant rise in PSA in the non high-risk subgroup only was observed," Dr. Pastuszak said," and there were more prostate cancer recurrences in the control group than the testosterone replacement therapy group," he added.
"This is a retrospective study. We need prospective clinical trials with longer follow-up because prostate cancer is such a slow-growing malignancy," Dr. Pastuszak told Medscape Medical News. "Ultimately, there are questions remaining about the impact of testosterone on prostate cancer in humans; we need to understand that relationship at the molecular level."
American Urological Association (AUA) 2012 Annual Scientific Meeting: Abstract 1488. Presented May 22, 2012.

Avoiding Prostate Cancer Screening Might Be Costly

E. David Crawford, MD, head of the section of urologic oncology at the University of Colorado Health Sciences Center in Denver, and colleagues presented an analysis of the recommendations in a late-breaking oral session here at the American Urological Association 2012 Annual Scientific Meeting.
This week, the USPSTF gave prostate cancer screening a grade of D (not recommended; harm outweighs benefits or no net benefit). However, the analysis by Dr. Crawford and colleagues suggests that avoiding prostate cancer screening might ultimately cost more in terms of treating advanced disease and missing significant numbers of cases.

American Urological Association (AUA) 2012 Annual Scientific Meeting May 19 - 23, 2012; Atlanta, Georgia

From Medscape Urology

Medscape Medical News, May 23, 2012
Medscape Medical News, May 23, 2012
Medscape Medical News, May 22, 2012
Medscape Medical News, May 21, 2012
Medscape Medical News, May 21, 2012
Medscape Medical News, May 19, 2012
Medscape Medical News, May 19, 2012
Medscape Medical News, May 19, 2012
·         What's Hot at AUA 2012?
Medscape Medical News, May 18, 2012

Solabegron Safe and Effective in Overactive Bladder

Smooth muscle relaxation during bladder filling is mediated by beta-adrenergic receptors, predominantly of the beta-3 subtype in humans. Agonists of this receptor can be effective in the treatment of urinary frequency, urgency, and urgency incontinence. Solabegron is a highly selective high-affinity beta-3 adrenoceptor agonist currently in clinical development for the treatment of OAB symptoms.

Nitrofurantoin—current concepts

Bacterial drug resistance has become a major concern for urologists in the treatment of urinary tract infection (UTI). One drug which has managed to avoid such resistance problems in its thirty years of use is nitrofurantoin. Nitrofurantoin is effective therapeutically for the treatment of acute lower tract infections, chronic UTI, and for the suppression of catheter-associated bacteria. On a prophylactic basis it is used to sterilize urine before TURP and to prevent chronic reinfection. Its unique mechanism of action, site specificity, achievement of high urinary levels and low serum concentrations, and its effectiveness against both gram-negative and gram-positive bacteria provide many advantages in UTI therapy that many of the newer agents do not. Adverse drug reactions, especially pulmonary toxicity, are extremely rare, and nitrofurantoin maintains an excellent safety profile.

Phase II Marker Lesion Study With Intravesical Instillation of Apaziquone for Superficial Bladder Cancer: Toxicity and Marker Response

We studied the ablative activity of intravesical apaziquone (EOquin™) on a papillary marker tumor and determined the incidence of side effects.
Materials and Methods
A total of 46 patients with multiple pTa or pT1 bladder tumors underwent visible lesion resection except for 1 marker tumor. Patients were then treated with 6 instillations of apaziquone at weekly intervals. The response was determined 2 to 4 weeks after the last instillation.
One patient withdrew informed consent and refused the last treatment due to side effects. A histologically proven complete response was seen in 30 patients. Progression to invasive stage was not observed. Local side effects in this study were comparable to those due to other chemotherapy instillations, such as mitomycin C and epirubicin, but less severe and less frequent compared to those of bacillus Calmette-Guerin instillations.
The histological complete response rate after 6 consecutive instillations of apaziquone in patients with superficial bladder cancer was 67% (95% CI 51 to 80). Local side effects were comparable to side effects due to other chemotherapy instillations.

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