Advances in the field of radiology have always been revolutionising healthcare. Speak of fusion imaging and one always thinks of PET-CT or PET-MRI. However, a blend of MRI and ultrasound technology is now available and has opened new possibilities in prostate imaging and biopsy targeting. By using this technology, doctors can not only find hidden tumours missed by conventional prostate biopsy but also reduce the number of biopsies performed on the patient. A rare and expensive technology fusion MRI/ultrasound is said to add value to the existing information available to doctors treating prostate cancer patients. This technology has proven to be of great value for detection of tumours in men with prior negative biopsies, but persistently elevated PSA levels.
Difficult to diagnose
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Prostate cancer is difficult to diagnose for a number of reasons. The size of the organ and its location, accessibility for inspection etc., all pose great challenges for doctors. “Assessment of the prostate malignancy is difficult because of the small size of the organ of origin, and delayed presentation of symptoms,” says Dr Venkataraman Bhat, Director, Radiology-Imaging Services, Narayana Health City, Bangalore. “Prostate cancer does not have specific symptoms in its initial stages, and its symptoms overlap significantly with that of benign prostatic hyperplasia,” explains Dr RK Gupta, Director and Head, Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon.
Prostate harbours malignancy in several asymptomatic patients, occasionally found incidentally. “Advanced prostate cancer patients are seen by either neurosurgeons or by orthopaedic surgeons, thus a delay in diagnosis is inadvertently made,” says Dr Kailash Mishra, Consultant, Radiation Oncologist, BNH HCG Cancer Centre, Bangalore. “The nocturia, hematuria and dysuria are confused with urinary tract infection and also with benign prostatic hyperplasia which is very common in elderly population,” he adds.
Cancers in other solid organs are usually detected by imaging and then biopsied for confirmation of diagnosis. “In case of prostate cancer, malignancy is usually suspected by a raised PSA or an abnormal nodule on physical examination and then multiple random biopsies are taken from the prostate to confirm the presence and the grade of tumour. More often than not, a prostate malignancy is not clearly visible on imaging. Moreover, a suspicious lesion on imaging may not be cancer at all,” explains Dr Gagan Gautam, Head of Urologic Cancer Surgery & Robotic Surgery, Medanta – The Medicity, Gurgaon. Moreover, the clinical course of prostate cancer in general is less stormy and protracted, sparing a small percentage of very aggressive forms. And the regular CT is not effective in detecting prostate cancer. “Imaging with CT scan takes a back seat in prostate cancer,” says Dr Mishra.
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A. T2-weighted axial MRI demonstrating a lesion in the left peripheral prostate. |
| Work flow of targeted prostate biopsy in 59-year old male with PSA 7.4 ng/ml, no palpable prostate lesion and prior negative biopsy Courtesy: urology.ucla.edu |
Imaging modality for prostate cancer
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Since diagnosis of prostate cancer is difficult it requires precise and quick imaging information. Many urologists would prefer an MRI exam but it is expensive and not always available. Hence ultrasound is used more frequently in India. “Prostate cancer imaging has been traditionally done by two modalities which have till recently, been independent of each other. For the diagnosis of prostate cancer, multiple biopsies are performed randomly from the prostate under transrectal ultrasound guidance. The objective is to ensure that all the areas of the prostate are adequately sampled in order to decrease the chances of missing a cancerous area,” explains Dr Gautam.
“Over the last few years, multi-parametric MRI (MP-MRI) is playing a major role in the diagnosis and staging of prostate cancer. With the help of various sophisticated imaging sequences such as dynamic contrast enhancement, diffusion weighted imaging and magnetic resonance spectroscopy and with the use of higher strength magnetic fields (3T) and endo-rectal coil, it is now possible to detect small cancerous lesions in the prostate and do an accurate local staging with a greater degree of confidence,” he adds.
“MRI is the modality of choice for imaging prostate cancer,” opines Dr Gupta. “Ultrasound and CT do not have adequate contrast to reliably diagnose prostate cancer,” he says. “Early prostate cancer is imaged using transrectal ultrasonography and MRI,” says Dr TK Padmanabhan, Senior Consultant, Radiation Oncology, KIMS Pinnacle Comprehensive Cancer Center, Kochi. “Patients having elevated PSA (more than 4 ngm/ml) or having suspicious hard nodules on digital rectal examination (DRE) are subjected to ultrasonography and MRI,” he adds. “Prostate cancer is initially imaged by transabdominal sonography. Additional high-quality information can be obtained through the transrectal ultrasound. Much more specific and accurate information is obtained using MRI,” says Dr Bhat.
However there are other methods of imaging that provide more sensitive information. “T2W imaging, dynamic contrast enhanced MRI, diffusion weighted MR imaging and MR-spectroscopy are all used for imaging prostate cancer,” informs Dr Madhavan Unni, Senior Consultant, Radiodiagnostics, KIMS Hospital, Kochi. “Isotope scanning, PET-CT and SPECT are also used for staging prostate cancer. Contrast enhanced ultrasonography and ultrasound elastography are new methods in ultrasonography which are being evaluated for prostate cancer imaging,” he adds.
Image-guided biopsy
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The small size of the organ and its origin pose a lot of challenges for biopsy. It has to be approached via the rectum, urethra or the penis. “Standard approaches for prostate biopsy are transrectal, trans-urethral and trans-perineal. Of these, ultrasound guided trans-rectal (TRUS) biopsies are most popular and are widely employed,” informs Dr Padmanabhan. But the TRUS-guided standard biopsies are cancer blind, so despite taking 12 biopsies there is always potential risk of missing the cancer. “One data says that these biopsies can miss up to one third cancers and half of the cancers are given lower grade on biopsy than what they turn out to be on surgery,” says Dr Gupta. Agreeing, Dr Mishra says, “Trans-rectal ultrasound-guided biopsy (TRUS) is the standard method of biopsy used for prostate but 12 core detection ratio is only 44.4 per cent and is a blind procedure too. There is a 20-30 per cent miss during first procedure, and with each additional biopsy session the rate of cancer detection decreases.”
Explaining the challenge, Dr Unni says, “Despite multi-core biopsies, less than one per cent of total gland volume is sampled. Many times, smaller lesions cannot be seen in ultrasonography and essentially the biopsies are non- targeted. Apex, lateral most and anterior parts of prostate are usually not adequately sampled. As mentioned before, close to 40 per cent of prostate cancers can be missed in biopsies also.”
Commenting on the limitations, Dr Bhat says, “In an ultrasound image normal and abnormal prostate are differentiated by difference in echogenicity. Occasionally contrast enhanced ultrasound augments diagnosis of detection of abnormal areas. Blind biopsies of prostate have a limitation of improper and non-representative sampling. Transrectal ultrasound-guided biopsies are more accurate, though technically more demanding. Despite being more accurate than blind biopsy, ultrasound is only able to biopsy basal part of the gland. Sizeable part of the gland remains beyond ultrasound reach.”
Fusion MRI/ USG is the answer
Experts believe that combination of two modalities can yield new and useful information. For prostate cancer MRI and USG is considered a safe procedure for prostate biopsy, and is widely being accepted. MRI and ultrasound techniques have different ways of unravelling normal and abnormal tissues. Information obtained from both techniques is complementary. Since the information is obtained from different modalities, they are reviewed separately, and in different contexts. “MRI being a more sensitive imaging technique for prostate cancer, data from MR-images can be extrapolated to a computer generated 3D model of prostate gland. This 3D dataset can be fused with images from specially designed ultrasound machines having controlled articulated arms and then used for precise targeted biopsies,” explains Dr Unni. “This method increases the sensitivity of prostate biopsies, than those performed with single modality imaging,” he adds.
“Localised CaP has proven difficulty for imaging,” explains Dr Mishra. “The MRI/US fusion technique distinguishes between small insignificant cancer and a lethal one, the former are more prevalent and need only ‘active surveillance,’ he adds.
Dr Gautam explains, “In this technique, an MP-MRI is done before the biopsy in a patient suspected to have prostate cancer. Any suspicious areas within the prostate are detected and categorised based on the level of suspicion on imaging criteria. This information is fed into the ultrasound machine, which labels and superimposes these suspicious areas on a transrectal ultrasound image of the prostate thereby targeting them for a biopsy. In recent studies, the detection rate of prostate cancer from these targeted areas has been found to be significantly higher than random biopsies.”
Which modality is better?
| Artemis (Eigen, Grass Valley, CA), is a device which allows biopsy site tracking with 3D ultrasound and fusion of real-time ultrasound with MRI. The device was installed at UCLA in early 2009 |
We know that MRI/US fusion imaging gives a composite set of information with accurate anatomical correlations for targeted biopsies but how does it compare to single modality imaging? “All modalities have their drawbacks. TRUS-guided biopsies are cancer blind and MRI-guided biopsies are too cumbersome, time consuming and costly,” opines Dr Gupta.
“On discussing the merits of only ultrasound or only MRI or MRI/ultrasound fusion, the opinion was that ultrasound has poor soft tissue localisation whereas only MRI can serve the purpose but it is always better to choose the best one available,” says Dr Mishra. “US/MRI fusion technique aids in systematic and targeted prostate biopsy to guide and record biopsy locations and to fuse MRI with real time USG,” he adds. Offering a different view, Dr Gautam says, “The same function can also be performed by ‘cognitive’ guidance, which implies studying the MRI films carefully prior to performing the biopsy and targeting the suspected areas with ultrasound without the fusion technology.”
“It is an obvious fact that this ‘non-fusion’ guidance would be extremely prone to error, specially since the distance between normal and abnormal areas in the prostate may just be a few millimetres,” he adds.
Growing concern
Prostate cancer is one of the most common causes of cancer in males and its cases have been increasing globally. Incidence is highest in Scandinavia with 22 per 100,000 population and lowest in Asia at five cases 100,000 population. Yet, in India the incidence of prostate cancer is increasing and about 20,000 cases are detected every year.
According to Indian Council of Medical Research (ICMR), by 2020 about 30,000 new prostate cancers will be detected every year. The distribution of prostate cancer in India varies. “In Delhi, it’s the second most common cancer in males. In Mumbai, it is the third most common cancer. In Bangalore, it is the fourth most common cancer in males. Incidence of prostate cancer is less in North Eastern states of India and it is not in the top 10 cancers in males, whereas in other states it is among the top cancers in males,” explains Dr Padmanabhan.
Need of the hour
With the rising number of prostate cancer patients in India, it is important that we find a good detection technique that would help doctors make informed decisions. “Combining information from MRI and ultrasound will add to accuracy of diagnosis. Fused images, when used on ultrasound platform, can also allow more accurate biopsy localisation,” says Dr Bhat. “Technology allowing fusion of ultrasound and MR images will certainly enhance the value and accuracy of information. This is a welcome addition to the available technology options,” he adds.
In spite of this, none of the hospitals in India are using MRI/ultrasound fusion imaging for targeted tissue sampling. “I am not aware of any centre wherein the fusion of MR and ultrasound images is done for prostatic evaluation. There are many vendors providing equipment capable of fusion technology which are routinely used in the West,” opines Dr Bhat. Dr Gautam agrees and says, “To the best of my knowledge, there are no centres in India yet, who are using this.”
However, many noted medical institutes in the US and Europe are using this fusion technology, not only for targeted tissue biopsies but also for grading of cancer. Besides cancer, this fusion imaging is also finding application in imaging rheumatoid arthritis among other diseases. As of now, its use and value in prostate cancer has been established. Vendors are researching and fine-tuning the technology further. New transducers are being designed, new combinations are being tested and results are highly promising.
“As techniques and technologies evolve in the future, it may help in improving detection rates, decreasing costs and morbidity and allow selective detection of significant prostate cancer while avoiding over detection of insignificant tumours which do not warrant treatment,” sums up Dr Gautam.