Hormone Blockade for Early-Stage Prostate Cancer

MARK SCHOLZ, MD

Being medical oncologists rather than surgeons—and being more impressed by the toxicity of surgery than by its effectiveness—my partners and I hypothesized back in the early 1990s that since testosterone inactivating pharmaceuticals (TIP) are powerful enough to reverse metastatic disease, they should be even more effective against early-stage disease.

Clinical Experience with TIP for Early Stage
In 2011, we published a scientific article in the Clinical Genitourinary Cancer detailing the twelve-year outcome for 73 men who embarked on TIP as primary therapy. In this group of men the average PSA was 9 and the average Gleason score was 7 (intermediate grade). Most of the men had tumors in their prostate large enough to be felt by digital rectal examination. Twenty-one of them maintained a low PSA indefinitely with a single course of TIP—they never needed a second cycle.

Another group of 24 men required periodic repeat cycles of TIP to keep their PSA less than five. In the remaining 28 men, after one or more cycles of TIP, the decision was made to undergo treatment with surgery, seeds or radiation.  However, the average time to treatment was 6.2 years after the first cycle of TIP. Only three of those 28 men ever relapsed after treatment. In summary, this study showed that initial remissions with TIP were universal and that even if the remission was not permanent, treatment with more radical therapy was delayed many years.

In 2012, we published another scientific study in The Prostate, in which we evaluated the effect of 12 months of TIP in 102 men. Twenty-two men were in the Low-Risk category, 30 were Intermediate-Risk and 50 were High-Risk. The median PSA was 7.8 and the median Gleason score was 3 + 4 = 7. The attainment of a clear biopsy after TIP followed by a sustained 7- year remission occurred in forty-five men. The likelihood of durable remission was dependent on the risk category: 82% of Low-Risk, 47% of Intermediate-Risk and 25% of men with High-Risk required no further treatment.

Monitoring TIP’s Effectiveness
One of the beauties of TIP is how easily its anti-cancer effects can be monitored with PSA. Although there is much debate about using PSA for cancer screening, PSA is an amazingly accurate tool for monitoring treatment response. In a study we published in Urology in 2007, we showed that more than 95% of men with newly-diagnosed disease drop their PSA to less than 0.05 within eight months of starting therapy. It’s a rare for cancers to continue producing PSAs above a threshold of 0.05 after six months of TIP therapy.  However, when these rare cancers occur, i.e. when an elevated PSA nadir occurs, it is a flashing sign that aggressive multi-modality therapy should be instituted.

What about Side Effects?
So what is the catch?  To this point TIP sounds like a very logical way to initiate treatment. Even if the disease is not arrested altogether, it delays progression for many years. And men who select TIP as initial therapy can always “jump ship” and undergo radiation or surgery. Delaying surgery or radiation with their potentially irreversible side effects makes sense considering the acclerating pace of medical progress. In this rapidly changing environment, postponing irreversible treatment for even five years is unquestionably an attractive proposition.

The catch is that while TIP side-effects are manageable, they are not trivial. Without attention to diet, notable weight gain occurs. Without regular resistance training and weight lifting, significant muscle weakness will ensue. While on treatment, the majority men lose their sex drive. A loss of sex drive is, however, different than impotence. With medications such as Viagra and Cialis most men on TIP can have erections sufficient for intercourse. Sex can be enjoyed, but it is not sought after with the usual male verve. There is also the potential for additional side effects such as breast enlargement, osteoporosis and hot flashes. As dire as these sound, they are preventable with common medications such as Femara, Prolia and progesterone. However, the side effects are cumulative and become more prominent the longer TIP treatment is continued.

Final Thoughts
Some men are concerned that their cancer will progress if “real treatment” like surgery or radiation is delayed. They forget that surgery and radiation only eradicate the “friendly types” of prostate cancer, the ones that remain contained in the gland. The real danger lies in the possibility of microscopic metastasis. Radiation and surgery have no effect whatsoever on cancer that has already spread. Only TIP circulates throughout the entire body attacking early-stage micro-metastasis in the lymph nodes or bones.

In my next blog, I will be discussing a new, more powerful type of TIP that has recently been approved by the FDA. The enhanced effectiveness of this new drug may enable a shorter course of treatment. And since testosterone levels in the blood remain normal throughout, the risk of lingering side effects should be eliminated.