https://www.bumc.bu.edu/gms/bioimaging/

Anonymous said... My PSA level has increased from 5.0 to 6.0 all in a matter of 2 weeks. I feel fine and there are no signs of anything being wrong. What's the best avenue to take to cure and/or prevent things from getting worse? February 22, 2012 3:34 AM

Changes of PSA levels may have several reasons. 

Cancer is one of them.

Physical irritation of the prostate: riding a bike or horse for example, which should be avoided before the PSA test.  Inflammation of the prostate. Benign enlargement of the prostate (BPH; Large prostates produce more PSA than small prostates).)... and other reasons may also cause elevated PSA levels.   

If concern persists, your urologist will discuss this with you, (for example, when the PSA level continues to rise, or rises fast) then a biopsy should be considered. If the biopsy is negative (no cancer found), and PSA levels continues to be concerning, I recommend MRI of the prostate (Magnet Resonance Imaging (a method using radio waves / magnetic fields to produce images of the prostate (without radiation/ no x-rays) for detection of possible cancer.  If MR images show suspicious lesions, those can be targeted either directly during MRI-guided prostate biopsies, or during ultrasound-guided biopsies, using the MR images (for example after fusion of MR and ultrasound images) as "map'  of prostate and suspicious targets. 

ANY unexpected change of PSA level should be discussed with your urologist, because cancer as reason has to be ruled out.  


Your urologist will know when to repeat the PSA test, when to recommend a biopsy, or when to treat a possible inflammation of the prostate.

"...could the clinical stage be up-graded to reflect a T2 or even T3 classification depending on the imaging results?"

"...when prostate cancer is found prior to biopsy, through the application of newer imaging techniques of the prostate, such as dynamic contrast-enhanced MR imaging and 3D MR spectroscopic imaging, and that prostate cancer is confirmed by subsequent biopsy, would the clinical staging, prior to treatment, still remain T1, or could the clinical stage be up-graded to reflect a T2 or even T3 classification depending on the imaging results?"

... was asked by David, who posted the following comment:

Greetings,

T1c prostate cancer is diagnosed because of an abnormal PSA in the setting of no palpable abnormality on Digital Rectal Examination and the cancer tumor is found in one or both lobes by needle biopsy.

In population screened situations, where a raised PSA is reported, a common clinical staging, utilizing the TNM classification, is T1c, which is tumor identified by needle biopsy. 

However, when prostate cancer is found prior to biopsy, through the application of newer imaging techniques of the prostate, such as dynamic contrast-enhanced MR imaging and 3D MR spectroscopic imaging, and that prostate cancer is confirmed by subsequent biopsy, would the clinical staging, prior to treatment, still remain T1, or could the clinical stage be up-graded to reflect a T2 or even T3 classification depending on the imaging results?

In other words, given that "magnetic imaging is now widely used for staging before treatment and accumulating data indicate the utility of this technique with magnetic resonance spectroscopy in staging and follow-up" , ( Imaging of Prostate Cancer. Oehr P, Bouchelouche K, Curr Opin Oncol. 2007 May;19(3):259-64) can the staging system reflect this improved imaging so as to better delineate T1 from T2 and T3 classification?

Thank you for your expertise,

David

The answer is yes.

Below you find the official and current TNM staging system issued by AJCC 2002 (The American Joint Committee on Cancer (AJCC) TNM staging system for Prostate, 6th edition). 

There it is defined clearly:" T1: Clinically inapparent tumor not palpable nor visible by imaging...Tumor found in 1 or both lobes by needle biopsy, but not palpable or reliably visible by imaging, is classified as T1c."

In other words, if reliably seen on Ultrasound or MRI, the tumor stage changes to T2 or T3, even if the tumor is not palpable (= the tumor is not felt by the urologist during the digital rectal examination).

See illustrations from the National Cancer Institute (NCI)

TNM Definitions Primary tumor (T) TX: Primary tumor cannot be assessed T0: No evidence of primary tumor T1: Clinically inapparent tumor not palpable nor visible by imaging T1a: Tumor incidental histologic finding in 5% or less of tissue resected T1b: Tumor incidental histologic finding in more than 5% of tissue resected T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA) T2: Tumor confined within prostate* T2a: Tumor involves 50% or less of one lobe T2b: Tumor involves more than 50% of one lobe but not both lobes T2c: Tumor involves both lobes T3: Tumor extends through the prostate capsule** T3a: Extracapsular extension (unilateral or bilateral) T3b: Tumor invades seminal vesicle(s) T4: Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall * [Note: Tumor that is found in one or both lobes by needle biopsy but is not palpable or reliably visible by imaging is classified as T1c.] ** [Note: Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is classified as T2 not T3.] Regional lymph nodes (N) Regional lymph nodes are the nodes of the true pelvis, which essentially are the pelvic nodes below the bifurcation of the common iliac arteries. They include the following groups (laterality does not affect the N classification): pelvic (not otherwise specified [NOS]), hypogastric, obturator, iliac (i.e., internal, external, or NOS), and sacral (lateral, presacral, promontory [e.g., Gerota], or NOS). Distant lymph nodes are outside the confines of the true pelvis. They can be imaged using ultrasound, CT, MRI, or lymphangiography and include: aortic (para-aortic, periaortic, or lumbar), common iliac, inguinal (deep), superficial inguinal (femoral), supraclavicular, cervical, scalene, and retroperitoneal (NOS) nodes. Although enlarged lymph nodes can occasionally be visualized, because of a stage migration associated with PSA screening, very few patients will be found to have nodal disease, so false-positive and false-negative results are common when imaging tests are employed. In lieu of imaging, risk tables are generally used to determine individual patient risk of nodal involvement. Involvement of distant lymph nodes is classified as M1a. NX: Regional lymph nodes were not assessed N0: No regional lymph node metastasis N1: Metastasis in regional lymph node(s) Distant metastasis (M)* MX: Distant metastasis cannot be assessed (not evaluated by any modality) M0: No distant metastasis M1: Distant metastasis M1a: Nonregional lymph node(s) M1b: Bone(s) M1c: Other site(s) with or without bone disease * [Note: When more than one site of metastasis is present, the most advanced category (pM1c) is used.] Histopathologic grade (G) GX: Grade cannot be assessed G1: Well differentiated (slight anaplasia) (Gleason score of 2–4) G2: Moderately differentiated (moderate anaplasia) (Gleason score of 5–6) G3-4: Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10)

If PSA of 3 can still indicate cancer, why is only a PSA > 4 suspicious?

...an anonymous reader asked.

A PSA level of 3 does not indicate cancer. 

Yet, it is possible to have a PSA of 3  with prostate cancer. 

 

PSA is a very successful screening test, and helped to detect and treat prostate cancer earlier. 

However, to make this screening test successful and efficient, thresholds had to be established.

Based on several very large studies these thresholds were set, because it was found, that with PSA levels below 4 the risk for prostate cancer is relatively low (see previous post Jan 28).

With PSA levels above 4 the risk was significantly higher.

These are statistical - empirical values. 

However, it is obvious,  that by setting a "threshold" (or cut-off) based on statistics (in contrast to personalized medicine), we always will have some patients who fall into the low risk group and do have cancer; and will find many patients with "elevated PSA" who have no cancer.

"If PSA is elevated, can ultrasound or MRI rule out cancer ?"

...was asked by an anonymous reader.

Neither Ultrasound nor MRI  can role out cancer completely. 

Ultrasound: is very useful to visualize the prostate during biopsy and other interventions. 

However, the prostate borders are not clearly seen.  Cancer, if big enough  and in locations closer to the rectum, can be seen, but not always.  New developments in ultrasound, especially contrast enhancement (a contrast agent is injected into the arm vein  - like in CT or MRI), and other new techniques, (currently investigated in research studies)  seem to make ultrasound better. 

MRI: is by far the best imaging modality for prostate at the moment. When performed right, the prostate gland, the capsule of the gland, the structures  around the prostate (like the neurovascular bundles and seminal vesicles) can be seen clearly; and cancer is much better seen on MRI than on Ultrasound or CT. If state-of-the-art MR imaging protocols are used, which include dynamic contrast enhanced MRI, or MR Spectroscopy, the results are even better, and most of the clinical relevant cancer are seen. With clinical relevant cancers are seen is meant, that tumors, which need clinical treatment, are picked up with MRI in most of the cases (up to 90-95% in experienced prostate MRI centers). MRI is not perfect (nothing is): very small tumors and in some cases even larger tumors are still not seen with MRI. 

Therefore, cancer can never be excluded completely. 

However,  if the PSA-level is elevated, yet, the experienced Urologist does not "feel" the cancer during his digital rectal exam (DRE; the urologist examines the prostate with his finger through the rectum); the Ultrasound is negative (does not show any suspicious area); and the MRI does not show any tumor, the chance that there is a cancer present, which needs immediate therapy is drastically reduced.  The urologist has to decide then, if he wants to perform a biopsy or not:  based on the patients history, PSA, DRE, findings on ultrasound and  - if performed  - findings of MRI. 

The advantages of prostate MRI are described and explained on several websites (see links on the right side). Currently,  MRI is generally performed only after cancer has been diagnosed with biopsy (for staging; is the cancer gland confined or not?); or after repeat negative biopsies and rising PSA (for detection); or after therapy and PSA relapse (for local recurrence).

"Does a PSA level of 6 mean that prostate cancer exists??"

This questions was asked by an anonymous person.

Thank you for this very important question!

The answer is no. 

But cancer is possible and further investigation (clinical exams) is necessary.  

[On the other hand, cancer is also possible with a PSA (Prostate Specific Antigen) level of 3]. 

PSA levels can be elevated due to several reasons: cancer, benign prostatic hyperplasia (enlargement of the prostate - in elder men; larger prostates produce more PSA), inflammation/infection (prostatitis), mechanical irritation (e.g. horse or bicycle riding), and ejaculation, and others.  

However, in case PSA is elevated further exams are indicated.  [a PSA level of 6  - before we know the size of the prostate  - has to be considered as elevated; levels between 4-10 are suspicious]: 

1) Digital rectal exam (DRE; Urologists examine manually the prostate), 2) trans-rectal ultrasound (TRUS), or 3) MRI (magnetic resonance imaging). 

Based on the results  of these exams, a decision has to be made if biopsy is necessary at this point.  

In other words: PSA levels between 4 and 10 ng/mL (nanograms per milliliter) are considered to be suspicious and should be followed by trans-rectal ultrasound imaging and, if indicated, prostate biopsy should be performed. Some urologists prefer to ask for MR Imaging prior to the biopsy to better locate any suspicious, "cancerous" area, and consequently target the biopsy.  

PSA is an excellent screening test and helps to detect prostate cancer early. Yet, PSA is false positive-prone (7 out of 10 men with PSA levels 4-10 will still not have prostate cancer) and false negative-prone (2-3 out of 10 men with prostate cancer have no elevation in PSA). Recent reports indicate that refraining from ejaculation 24 hours or more prior to testing will improve test accuracy.

This blog was created for patients, technologists, clinicians and radiologists to address questions and ideas about prostate imaging.

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