Over 1,200,000 men around the globe are diagnosed with prostate cancer (PCa) every year. They don’t all have the same disease, however. There are numerous cell lines with varying characteristics: “The disease is very heterogeneous in terms of grade, genetics, ploidy, and oncogene/tumor suppressor gene expression, and its biological, hormonal, and molecular characteristics are extremely complex.”^[i] To further complicate matters, an individual’s PCa may actually have a mix of two or more cell lines.

Some of these cell lines are relatively rare but potentially lethal. They have different types of patterns that microscope analysis can reveal—and it’s very important that they are identified quickly and treated appropriately. Even if a particular cell line is in a small minority, it still means thousands of men have it, and their lives may be in danger. If undetected, the risk level of the PCa will be underestimated, and the treatment plan may be inadequate to control the disease. Thus, the biopsy process is key to finding these threats.

Ductal and intraductal PCa

Two such patterns are intraductal carcinoma of the prostate (IDC-P) and ductal adenocarcinoma. Each of them is linked with worse outcomes. We know this from whole gland studies that analyze surgically removed glands and follow the patients for a period of years. When presurgical records (age, PSA, Gleason grade, etc.) are correlated with 1) post-surgical factors (Gleason score upgrade, microscopically identified cell patterns), 2) subsequent biochemical recurrence (rising PSA), and 3) cancer-specific death, it is evident that patients found to have IDC-P and/or ductal patterns have greater rates of recurrence that occurs earlier, and they are more likely to die from their disease than patients without these patterns.

IDC-P or ductal cell patterns are found along with the most common type of PCa (acinar adenocarcinoma). While rarely found in low-risk disease, they become more prevalent in intermediate-risk and high-risk PCa, and raise the chances that ordinary PCa will progress in aggression and advance beyond the gland. A 2020 paper^[ii] by a team of Australian researchers gives detailed insight into each type:

• IDC-P shows “expansive proliferation” of cancer cells into the ducts, or small passages through which enzymes are secreted into semen. These invasive cells have what’s called cribriform architecture, a bit like holey Swiss cheese. These features of IDC-P resemble other atypical lesions, so they are sometimes misdiagnosed. “Patients with IDC-P at biopsy or prostatectomy are more likely to have higher Gleason grade acinar adenocarcinoma, more advanced pathological stage, and worse clinical features, such as extraprostatic extension and regional lymph node involvement.” Also, IDC-P is linked with early biochemical recurrence after radiation; after surgery, recurrence happens earlier even if there is hormone ablation or chemotherapy.
• Ductal adenocarcinoma can be recognized by a different structure called papillary architecture that looks like long, thin “fingers”. It too can have some features that make it confusing to distinguish, and it can coexist with IDC-P or occur on its own, but it is more likely to occur with high grade adenocarcinoma. It too can invade the ducts, and like IDC-P it is a sign of poor prognosis and likelihood of progression. “Tumors containing ductal adenocarcinoma have higher Gleason grade, tumor stage, volume, and incidences of extraprostatic extension, seminal vesicle invasion, positive surgical margins, and lymph node metastases.” Recurrence is more likely to happen, and sooner.

From the viewpoint of cellular biology, both types have molecular abnormalities that lead to genomic instability and damaged DNA repair pathways. These are not unique to PCa, but exist in other cancers such as certain breast cancer lines. It seems that aggressive cancer cells are more likely to acquire these features. This sounds dark, but there are bright rays of hope.

Consensus descriptions, better pathology, genomic testing and high-tech imaging enable better diagnosis even if patterns are ambiguous. By identifying these patterns and studying their molecular biology, treatments can be developed in order to tailor therapies to an individual’s PCa. As Lawrence, et al. state, “It’s essential to know what is growing in patient tumors.”

In-bore MRI-targeted biopsy

Today, targeted biopsy guided by real-time live multiparametric MRI (mpMRI) affords patients a precise and accurate opportunity to obtain tissue samples most likely to contain IDC-P or ductal patterns (if present) due to its “direct lesion-needle visualization and ability to identify and correct for unexpected tissue displacement…”^[iii] Research continually demonstrates the superiority of prostate biopsy done in the bore (tunnel) of the magnet, over the standard randomized TRUS biopsy and even over fusion biopsy^[iv]. To sum up just a few points:

• mpMRI visually depicts prostate tissue differences that ultrasound (TRUS) is blind to
• Fusion has the potential for error when co-registering (merging) previously captured MRI images with real-time TRUS^[v]
• The 12 or more needles necessary for randomized TRUS biopsy raise chances of biopsy side effects such as bleeding and infection
• It is commonly recommended to add systematic random TRUS sampling to fusion targeted biopsies^[vi], also raising side effect risks
• In-bore, real time live mpMRI biopsies use the fewest needles because the scan clearly shows the location, size and shape of suspicious area(s)
• In-bore MRI guidance allows placement of needles into the core of the lesion, which is where the most aggressive or aberrant cells are likely to be^[vii]—thus giving the most effective procedure for capturing IDC-P and ductal disease.

Why entrust your prostate to any other biopsy method? No matter how rare dangerous patterns are, it’s not worth gambling that they’re not there, especially in cases of intermediate-risk PCa or beyond.

The simple bottom line is, in-bore MRI-guided targeted biopsy is today’s best insurance against missing a rogue cell line. For more information, contact the Sperling Prostate Center.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Russell P.J., Kingsley E.A. (2003) Human Prostate Cancer Cell Lines. In: Russell P.J., Jackson P., Kingsley E.A. (eds) Prostate Cancer Methods and Protocols. Methods in Molecular Medicine™, vol 81. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-372-0:21
[ii] Lawrence MG, Porter LH, Clouston D, Murphy DG et al. Knowing what’s growing: Why ductal and intraductal prostate cancer matter. Sci Transl Med. 2020 Mar 4;12(533):eaaz0152.
[iii] Costa DN, Goldberg K, de Leon AD, Lotan Y et al. Magnetic Resonance Imaging-guided In-bore and Magnetic Resonance Imaging-transrectal Ultrasound Fusion Targeted Prostate Biopsies: An Adjusted Comparison of Clinically Significant Prostate Cancer Detection Rate. Eur Urol Oncol. 2019 Jul;2(4):397-404.
[iv] Prince M, Foster BR, Kaempf A, Liu JJ et al. In-Bore Versus Fusion MRI-Targeted Biopsy of PI-RADS Category 4 and 5 Lesions: A Retrospective Comparative Analysis Using Propensity Score Weighting. AJR Am J Roentgenol. 2021 Sep 9;1-8.
[v] Venderink W, de Rooij M, Sedelaar JPM, Huisman J, Futterer J. Elastic Versus Rigid Image Registration in Magnetic Resonance Imaging-transrectal Ultrasound Fusion Prostate Biopsy: A Systematic Review and Meta-analysis. Eur Urol Focus. 2018 Mar;4(2):219-227.
[vi] Borghesi M, Bianchi L, Barbaresi U, Vagnoni V et al. Diagnostic performance of MRI/TRUS fusion-guided biopsies vs. systematic prostate biopsies in biopsy-naïve, previous negative biopsy patients and men undergoing active surveillance. Minerva Urol Nephrol. 2021 Jun;73(3):357-366.
[vii] Costa DN, Goldberg K, de Leon AD, Lotan Y et al. Magnetic Resonance Imaging-guided In-bore and Magnetic Resonance Imaging-transrectal Ultrasound Fusion Targeted Prostate Biopsies: An Adjusted Comparison of Clinically Significant Prostate Cancer Detection Rate. Eur Urol Oncol. 2019 Jul;2(4):397-404