A small percentage of men in a prostate cancer study complained that their penis seemed shorter following treatment, with some saying that it interfered with intimate relationships and caused them to regret the type of treatment they chose.
Complaints were more common in men treated with radical prostatectomy (surgical removal of the prostate) or male hormone-blocking drugs combined with radiation therapy, according to the study by researchers from Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC). No men reported a perceived shortening of their penis following radiation therapy alone.
The study’s findings, which are being published in the January issue of the journal Urology, are based on surveys completed by physicians of 948 men treated for prostate cancer and who had suffered a recurrence of the disease.
Twenty-five men (2.63 percent of the group) complained of smaller penises after treatment – 3.73 percent for surgery, 2.67 percent for radiotherapy plus androgen deprivation therapy (ADT), and 0% for radiotherapy alone. Radiotherapy included both radiation administered by an external x-ray machine, and brachytherapy – the implantation of radioactive seeds directly into the prostate.
The scientific team, led by Paul Nguyen, MD, a radiation oncologist, and medical student Arti Parekh, said it is the first study to link men’s perceptions of a reduction in penis size to lowered life satisfaction, problems in emotional relationships, and misgivings about the specific form of prostate cancer treatment they chose.
Nguyen said that the potential side effect of a smaller penis is well-known among physicians and surgeons, said Nguyen, “but it’s almost never discussed with patients, so it can be very upsetting to some men when it occurs. Patients can deal with almost any side effect if they have some inkling ahead of time that they may happen.”
The addition of short-term androgen-deprivation therapy to external-beam radiation therapy improved overall and disease-specific survival in men with nonbulky localized prostate cancer and prostate-specific antigen (PSA) levels up to 20 ng/mL, as reported recently in The New England Journal of Medicine. The benefit of the addition of short-term Christopher Jones, MDandrogen-deprivation therapy was seen mainly in men with intermediate-risk disease, not low-risk disease, in this large, randomized, phase III international trial.
A caveat about these findings is that the radiation techniques used in this study were those used in 1994, when the study was initiated. More sophisticated techniques now in use deliver higher doses than what was possible 17 years ago. The benefit of short-term androgen-deprivation therapy has not been proven with the newer techniques, said lead author Christopher Jones, MD, a radiation oncologist at Radiological Associates in Sacramento, California.
Current Practice
Currently, most patients receive intensity-modulated radiation therapy, and many opt for treatment with brachytherapy (delivered via seeds [low-dose] or catheter [high-dose]). These newer techniques are associated with improved efficacy, Dr. Jones noted, which raises the question of the value of short-term androgen-deprivation therapy when added to modern radiotherapy techniques in intermediate-risk prostate cancer.
“It is not correct to routinely give short-term androgen-deprivation therapy to all patients on high doses of radiation delivered by modern techniques,” Dr. Jones stated.
The ongoing Radiation Therapy Oncology Group (RTOG) 0815 study is designed to answer the question of whether short-term androgen-deprivation therapy should be given with high-dose radiation, he explained. That study is currently accruing over 1,500 intermediate-risk patients who will be randomly assigned to high-dose radiation (physician’s choice of technique) with or without short-term androgen-deprivation therapy (6 months in the new study).
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By Alice Goodman
The report’s authors said physicians should discuss the possibility with their patients so that they can make more-informed treatment choices.
There were no direct measurements of penis size either before or after treatment, said the researchers. Nor did the patients’ physicians specifically ask about this side effect; the issue was brought up by patients in conversations with their doctors. For this and other reasons, the authors of the new study suggest that the problem is likely more common than reported in the survey.
“Prostate cancer is one of the few cancers where patients have a choice of therapies, and because of the range of possible side effects, it can be a tough choice,” said Nguyen. “This study says that when penile shortening does occur, it really does affect patients and their quality of life. It’s something we should be discussing up front so that it will help reduce treatment regrets.”
The likelihood and magnitude of penis shortening as a consequence of treatment have not been well studied, said the researchers. However, Jim Hu, MD, a surgeon at the University of California, Los Angeles Medical Center and a co-author of the study, said “Previous studies have concluded that there is shortened penis length following prostatectomy. This is most common with non-nerve sparing surgery, as this may result in fibrosis and atrophy of erectile tissue due to damage to nerve and vascular structures.” The present study did not find much difference on that score.
Androgen-deprivation Therapy plus Radiation Proven as Standard of Care for High-risk Prostate Cancer
A combined-modality approach of androgen-deprivation therapy plus radiation therapy achieves a substantial survival benefit over androgen-deprivation therapy alone in patients with locally advanced prostate cancer according to final analysis of an intergroup randomized phase III study conducted by the National Cancer Institute of Canada, Southwest Oncology Group, and UK Medical Research Council. At a median follow-up of 8 years, both overall survival and disease-specific survival were significantly improved by combined-modality therapy, and the combined therapy was well tolerated, as reported at the 54th Annual Meeting of the American Society for Radiation Oncology (ASTRO).
Level 1 Evidence
“Combined-modality therapy with androgen deprivation plus radiation should be considered the standard of care for locally advanced prostate cancer. The benefits of this therapy should be discussed with all patients,” said presenting author Padraig Warde, MD, Princess Margaret Hospital, Toronto, Canada. He said that combined-modality therapy is the only guideline-recommended primary therapy with level 1 evidence, and that the optimal duration of androgen-deprivation therapy remains to be defined.
The study randomly assigned 1,205 men with a median age of 69.7 years in a 1:1 ratio to androgen-deprivation therapy alone or androgen deprivation plus radiation. About 90% had T3/T4 disease and about 10% had T2 or lower-stage disease. About 81% had Gleason score ≤ 7. Continuous androgen-deprivation therapy was either bilateral orchiectomy or a luteinizing hormone–releasing hormone agonist. Radiation was delivered to the prostate, plus or minus seminal vesicles with or without pelvic node irradiation. An antiandrogen was given for 2 weeks, with an option to continue; 72% in the combination therapy group had pelvic nodes irradiated.
Ten-year overall survival was significantly improved, from 49% in the androgen-deprivation therapy–alone group to 55% in the combined-modality group, representing a survival improvement that was statistically significant (P = .0003). Androgen-deprivation therapy plus radiotherapy significantly improved disease-specific survival as well, with 134 deaths due to prostate cancer and/or its treatment on androgen-deprivation therapy alone and 65 deaths on the combined-modality therapy arm, representing a 54% improvement with combined-modality therapy (P < .0001).
Adding radiation to androgen-deprivation therapy resulted in a small detrimental effect on late gastrointestinal toxicity, specifically greater than grade 2 proctitis (0.3% on androgen-deprivation therapy alone vs 1% for combined-modality therapy), but the difference was not statistically significant.
The study’s subjects were men enrolled in a registry called COMPARE that collects data on patients whose prostate cancer shows signs of recurring after initial treatment. Of the 948 men in the study, 22 percent were younger than 60 and the majority were in their 60s, 70s and 80s. Just over half – 54 percent – had undergone surgery to remove their cancerous prostate, while 24 percent received radiation therapy combined with hormone-blocking treatment, and 22 percent had radiation therapy alone.
In an editorial comment accompanying the report, Luc Cormier, MD, PhD, of Dijon University Hospital in France said the study “is really of interest because of the number of patients and that it included other treatment methods in addition to radical prostatectomy.”
The surveys of the men did not report on their sexual functioning. Cormier observed that “sexual activity needs to be thoroughly measured owing to the obvious relationship with the patients’ perception of penile length.”
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Other authors are from Dana-Farber, the University of Connecticut, and the University of Texas M.D. Anderson Cancer Center.
The research was supported by an anonymous family foundation along with other foundation funding.
About Dana-Farber Cancer Institute:
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult care with Brigham and Women’s Hospital as Dana-Farber/Brigham and Women’s Cancer Center, and it provides pediatric care with Boston Children’s Hospital as Dana-Farber/Children’s Hospital Cancer Center. Dana-Farber is the top-ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding.
About Brigham and Women’s Hospital:
Brigham and Women’s Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs more than 15,000 people. The Brigham’s medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by $640 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses’ and Physicians’ Health Studies, OurGenes and the Women’s Health Initiative.
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Teresa Herbert
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Dana-Farber Cancer Institute
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