Once upon a time, there was no treatment for prostate cancer. Then came radical prostatectomy (surgical removal of the whole gland) and whole gland radiation, and for a long time these take-no-prisoner approaches were the only potentially curative treatments. In 1999, cryotherapy (freezing) was approved for reimbursement by Medicare, adding minimally invasive total gland destruction (ablation) to the list. Despite whole-gland treatment, prostate cancer came back in about 25% of cases.
In many cases, recurrence was likely due to the fact of underdiagnosis because TRUS biopsy sometimes missed high grade, aggressive cancer. However, there may be particularly deadly cell lines that behave differently and seem to defy whole gland treatments. In any event, recurrence or spread is typically discovered only when a man’s post-treatment PSA begins to rise. Better identification of risk factors was needed as well as probability algorithms to predict the odds of recurrence based on combinations of risk factors such as PSA and its variants, Gleason score, stage, patient age, etc. Family history is also one of those factors, and I will return to it.
While knowledge of risk factors was increasing, a revolutionary “subradical” (less than total) approach to treating prostate cancer evolved. Interest in focal therapy using extreme heat or cold led to the development of devices that could deliver precise, image-guided thermal energy to the tumor with minimal risk to healthy tissues. Now the challenge had become more complex: How to calculate an individual patient’s risk level as accurately and comprehensively as possible, and then how to match the best treatment to the disease? This is where the problem of family history comes in. If all other factors, including 3T multiparametric MRI scans and targeted biopsy, suggest a man is a candidate for focal laser ablation, does having a first degree relative (father, brother) with the disease rule our focal therapy?
There is no one right answer. A general principal is suggested by Eeles et al. (2014) who point out that “… understanding the genetic risks of prostate cancer might inform predictions of treatment responses and toxicities, with the goal of personalized therapy.”[i] However, until all the mysteries of cancer are revealed, treatment decisions must be made on a case-by-case basis.
First, hereditary prostate cancer affects only a small minority of patients. According to the National Institutes of Health, “From 5% to 10% of prostate cancer cases are believed to be primarily caused by high-risk inherited genetic factors or prostate cancer susceptibility genes.”[ii] Although this is a small proportion of prostate cancer cases, it now appears that some of the inherited gene mutations are more dangerous than others, suggesting that “…familial PC is a genetically heterogeneous disease, many gene loci rather than a specific major susceptibility gene predisposing to it.”[iii] Even with a genetic predisposition, other variables such as the environment can influence whether or not prostate cancer becomes active.
The problem is significant overlap between the molecular characteristics of sporadic prostate cancer (no family history) and those of hereditary prostate cancer (family history). A Dutch study found that the majority of single nucleopeptide polymorphisms (a common type of genetic variation in DNA organization) between sporadic and hereditary prostate cancer are too similar to be able to pin down the role of hereditary factors in developing prostate cancer, or having it recur after treatment.
At the Sperling Prostate Center, we believe family history matters, especially if a father or brother was diagnosed with prostate cancer before age 65 since statistics show this as a higher risk factor. In such cases, we recommend additional genomic testing to rule out biomarkers that suggest a particularly lethal form of the disease may be present. Our diagnostic protocol takes into account standard-of-care risk factors as well as the results of our 3T multiparametric MRI scans, and we believe in MRI-guided targeted biopsy into the most suspicious areas.
No prostate cancer treatment comes with a guarantee. We do not want to put our patients at risk of recurrence. We must be particularly cautious with focal treatment because we leave behind untreated prostate tissue. We do all we can, but are ever mindful that microscopic disease can escape detection and identification.
Our patients who have a hereditary history of prostate cancer, especially first degree relatives—and let’s not forget that a mother or sister diagnosed with certain lines of breast cancer must also be taken into account because of the similarities between prostate and breast cancer—deserve special counseling. On one hand, we have treated many men with one or more close relatives who had prostate cancer, and our patients diligently stick to our monitoring protocol after treatment. On the other hand, we respect that not every patient with a family history of prostate cancer will be comfortable with the possibility of an increased risk of recurrence when we still don’t know everything about how cancer cells behave. We understand that opting for radical treatment means they will sleep more soundly at night, even knowing they must still monitor to make sure prostate cancer hasn’t come back.
We are optimistic that today’s questions about prostate cancer will be resolved by advances in research and analysis. Until then, we equip our patients with the best possible diagnostic methods to help those with a family history of prostate cancer to make the decision that is right for them.
[i] Eeles R, Goh C, Castro E, Bancroft E et al. The genetic epidemiology of prostate cancer and its clinical implications. Nat Rev Urol. 2014;11:18-31.
[iii] Alberti, C. Hereditary/familial versus sporadic prostate cancer: few indisputable genetic differences and many similar clinicopathological features. Eur Rev Med Pharm Sciences. 2010;14:31-41.