I subscribe to an e-magazine called Prostapedia. The National Alliance of State Prostate Cancer Coalitions publishes the quarterly Prostapedia Magazine and the weekly Prostapedia Digests. They feature informal conversations with physician thought leaders, patients, and activists in prostate cancer. They are highly informative, with concise discussions of various prostate cancer topics.
The December 2023 Prostapedia Magazine featured the topic of side effects and contained an intriguing interview with John Mulhall, M.D.
Dr. Mulhall is the Director of the Male Sexual and Reproductive Medicine Program at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City.
He mentioned three restorative medicine therapies for erectile dysfunction that are cash-based businesses with no U.S. Food and Drug Administration (FDA) approval:
Low-intensity shockwave therapy (LISWT)
Platelet-rich plasma (PRP)
Stem cell therapy
He says MSKCC doesn't offer these therapies for the following reasons:
They are not FDA-approved.
More high-quality large study data is needed to show that they are effective in humans.
There is concern that shockwave and stem cell therapy might reactivate cancer in patients who have had a pelvic malignancy.
Research analysis with LISWT shows a placebo response of 30% - 35%.
He touts his program by saying,
"We are one of the most avid penile rehabilitation programs in the world."
His program is for men who have undergone radiation to the pelvis and any radical pelvic surgery, including radical prostatectomy, radical cystectomy, and low rectal cancer surgery. MSKCC does about 1000 prostatectomies a year, and between him and his colleague, they see about 600 new prostatectomy patients a year.
Because his program's services are in such high demand from MSKCC patients, they see only outside patients with Peyronie's disease. Peyronie's disease is fibrous scarring of the penis resulting in a curvature of the penis with painful erections.
The Sexual Medicine Society of North America (SMSNA) offers a provider directory to help you locate a sexual medicine provider in your area.
Penile rehabilitation
Dr. Mulhall says that in a classic rehab program, patients see physicians for their first visit and then a nurse practitioner for all follow-up visits unless they are not responding to injection medicine, have low testosterone levels, or have Peyronie's disease.
They attempt to see all patients preoperatively to let them know what to expect and tell them:
You won't ejaculate after prostatectomy.
You have at least a 60% chance postprostatectomy of at least one event of climacturia (orgasm-associated incontinence)
You have a 20% chance of climacturia consistently over the first year.
You have a 15% chance of orgasmic pain, usually short-term.
Phosphodiesterase inhibitor therapy
The first phase of penile rehabilitation is two weeks before and six weeks after surgery. Men will take low-dose sildenafil (Viagra) or tadalafil (Cialis) at bedtime, starting two weeks before and two weeks after surgery. During weeks three, four, five, and six, they increase the dose to a full-dose pill at bedtime. Then, they will follow up in the clinic six weeks after surgery.
The concept of using phosphodiesterase 5 (PDE5) inhibitors like sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra, Staxyn), and avanafil (Stendra, Vivus) is known as endothelial preconditioning because these drugs are potent endothelial protectants.
The endothelium lines blood vessels, and Dr. Mulhall points out that the penis is laden with endothelium and is like a big artery when erect and like a big vein when flaccid. He says there is value in doing everything possible to upregulate and protect the endothelium, including tight control of hypertension, dyslipidemia, and diabetes.
When the men follow up six weeks after surgery, they ask them, "When you took the full dose, did you get a penetration-hardness erection?" Only 15% of men within the first six months of surgery are PDE5 inhibitor responders.
Even in men who underwent nerve-sparring surgery, this low response rate, he says, is because "the nerves go to sleep for 9 - 12 months, and it takes another 9 - 12 months for them to wake up fully."
Dr. Mulhall emphasizes that erectile function recovery is an 18 to 24-month timeframe. Men who are pill responders take a maximum dose pill twice a week and a low dose pill on the other nights.
He says that regarding erectile dysfunction, he tells men that they might do well at one month but then see a dip in function. That's because 25 - 40% of men who are functional at six weeks will lose that function at four months.
85% of men will not be pill responders, and they go straight to injection therapy. Later, they try to transition patients from injections back to pills.
Injection therapy
Injection therapy consists of the vasodilators papaverine, phentolamine, and prostaglandin E1 as Trimix or Bimix, which is papaverine and phentolamine. A compounding pharmacy mixes the drugs and supplies a kit to patients who inject the mixture at the base of their penis.
The side effect of injection therapy is priapism, a prolonged erection. The chance of that happening in a program with a sound education system is uncommon at around 0.5%.
Importance of nocturnal erections
Dr. Mulhall points out that we get three to six erections every night after puberty. The purpose of those erections is to bring in blood flow, oxygen, and stretch. Men who don't get good nocturnal erections and aren't sexually active develop structural changes in erectile tissue—the you-don't-use-it-you-lose-it concept.
They try to imitate that in penile rehabilitation to give men erections to protect the erectile tissues.
He notes that the combination of prostatectomy, radiation, and androgen deprivation therapy is lethal to erectile tissue. 95% of those men will have permanent structural damage in their erectile tissue, and 50% of them won't respond to injection therapy.
If the patient has had or is about to have a combination of therapies, they need to get in and see somebody like him sooner rather than later if intercourse is their focus.
Interestingly, he only discussed vacuum devices near the end of the interview. When he did, he said, "The problem with a vacuum device, of course, is that it brings in old blood. It's not oxygenated blood." That tells me he isn't a fan of those devices.
Patients should advocate for themselves
The article concludes by emphasizing that patients should advocate for themselves. And that patients need to define what their long-term sexual function goals are before surgery or any other type of treatment.
He says that before treatment, the patient is just thinking, "Get rid of my cancer. Get rid of my cancer." They don't focus on sexual issues until they're six months posttreatment when they say, "I haven't had an erection in six months." Then they start worrying about it. The time to think about it is before they see the doctor.
The next newsletter discusses my experience with extracorporeal blood oxygenation and ozonation (EBOO) therapy.
Until then, stay healthy.
Much love,
Keith