Thursday, December 3, 2015

An Excellent Contribution to the Literature

The book by Mydlo and Godec, Prostate Cancer, is an exceptionally good text for practicing urologists and residents to get an understanding of the current understanding of this disease, prostate cancer (PCa). PCa is a complex disorder, and is unlike many other cancers. On the one hand almost all PCas are indolent, namely the patient will most likely dies of something else, but the small percent that have an aggressive form die very rapidly. The primary tool for detection has been the PSA tests which were virulently attacked by the USPTF. It can be argued that the data they based their opinion on was flawed but we leave that for time to tell, unfortunately at the cost to the patient. The genetics of PCa is also highly complex.

Unlike so many other cancers where we can identify a specific target such as BRAF in melanoma, BRACA in breast cancer and ABL fusion in CML, PCa is a mass of speculative genetic changes. Also the treatment of PCa is becoming more problematic. The options are several; surgery, radiation, implants, and even “watchful waiting” which in a sense is let hope and see what happens. The problem is that PCa metastasis is insidious and unlike breast or melanoma the path is circuitous and uncertain.

This book is introduced at a time when all of these issues are facing the physician. The question is; what does the physician recommend as a course of action to a patient? All too often the patient presents with a diagnosed PCa and based upon the patient’s own investigations finds his path to a recommended therapy. Whether that is the best for this patient is usually uncertain.

On p3 the authors open with a direct assessment of the USPTF, one which I would strongly recommend reading for any practitioner. It is short, well written and on point. This in a sense sets this rest of the work in clear perspective; unlike the USPTF, this is a “what is the best for the patient” work.

The book is structured along standard lines.

The first several chapters deal with a wide variety of current issues such as the genetics, the androgen receptor issues, and fusion. All are done at a reasonably high level for the practitioner. This is clearly not a book on the detailed genetic issues associated with PCa. Chapter 5 is an interesting chapter since it discusses the issues of Gleason 6 and is it even a cancer. This is a compelling question since as we are discovering the genetic makeup is often more telling and that may mean the genetic makeup of the most aggressive cell. Chapter 6 is another significant chapter since it deals with HGPIN. HGPIN has for a decade or more been synonymous with a progression to PCa. However that is not inevitable. The interesting cases are those where there is a HGPIN at initial biopsy and then it disappears and never returns. The question then is; how significant a prognostic issue is HGPIN?

Chapter 11 discusses MRI imaging in localized PCa. MRI imaging is becoming more common and is becoming an element in integrated biopsies with real time ultrasound. This is a useful chapter for the urologist to become familiar with an imaging technique which will become a more integral part of diagnosis and prognosis. However as with all modalities it may add significantly to the costs and also may cause increased biopsy covers for what may not be significant observations.

Chapter 13 is an excellent discussion on PSA screening. PSA is a useful but sometimes problematic measure. PSA increases with prostate volume and age as well as with pathological changes. Differentiating them is complex. The physician must balance reasonableness with the risk of being too insensitive to the changes. Chapter 17 discusses hereditary PCa. This is mostly a discussion of genetic inheritances that result in PCa. However we also know that there is a strong correlation between first degree relative PCa and PCa in the patient. This is correlative and not causative, whereas what in in this chapter seems to be much more causative.

Chapters 26 thru 41 discuss the complexities of surgical treatment and the presentation is clear and up to date. Chapters 42 thru 48 discuss radiation therapies with equal presentation. Chapters 52 thru 57 discuss some advanced issue of PCa therapy. This includes several biologics as well as androgen therapies.

Chapter 66 is an interesting chapter in that it discusses new markers for diagnosis and prognosis. On the diagnosis side there are many ways to enhance PSA and related measures including PCA3. One of the recent tests such as 4K have seemed to be of some use in assessing the chance of there being PCa prior to biopsy. Although I have had experience with this test and positively specifically it is still as I write this not FDA approved. There are also almost a dozen genetic tests used on PCa cells after biopsy to ascertain a prognosis for subsequent aggressive potential. Many of these are still being tested but generally they also provide guidance. However the conundrum is using them for prognosis when the result is poor and there is no significant treatment available.

Overall this is an excellent up to date summary of PCa, its diagnosis, prognosis, treatment and the state of the science that surrounds it. It clearly meets the needs of the practitioner. Its weakness in my view, and that of one involved more deeply on the genetics side, is that it would have been helpful to have delved a bit more deeply in the genetics of PCa. Unlike many other cancers PCa is highly heterogeneous and it seems that each week one sees another several genes putatively involved. Thus one can appreciate perhaps avoiding this area since it may be out of date by publication.

This is an excellent and up to date text and a worthy addition to what is currently available.