Luca Incrocci1
(1)
Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, 5201, 3008 AE, The Netherlands
Luca Incrocci
Email: l.incrocci@erasmusmc.nl
Pelvic irradiation constitutes the primary or adjuvant treatment for a large number of both female and male cancers: Endometrial, cervical, vaginal, and vulvar cancer in females, prostate cancer in males, and colorectal, anal, and bladder cancer in both males and females. In case of extensive colorectal, anal, bladder, or vulvar cancers, radiotherapy may be given before surgery to decrease the tumor volume and following surgery in case of nonradical resection margins.
We will describe immediate complaints and late complications of radiation treatment.
10.1 Immediate Complaints
The mucous membranes are very sensitive for radiotherapy and react within days. Severe acute mucosal erythema and desquamation can cause diarrhoea, rectal bleeding, bladder irritation, hematuria, and urinary incontinence. In the vagina, it can cause itching, burning, and dryness. The irradiated skin can react with dryness, itching, blistering, or peeling. A more general symptom of the first period after radiation is fatigue.
These complaints will cause a temporary reduction in sexual expression and intimacy, but in general they do not cause permanent sexual dysfunction.
Women report a feeling of lack of femininity, sexual attractiveness and confidence, besides being distressed by vaginal bleeding, vaginal pain, and vaginal dryness, resulting in fear of having sex and less sexual enjoyment.
The early disturbances of the skin usually disappear within 2–4 weeks after the radiation therapy and the mucous membrane disturbances within 3 months.
10.2 Late Complications
Pelvic radiation may cause severe sexual and other complications. Organ, vessel, and nerve-related radiation injury are equally reported, and may account for associated organic and, in the longer term, potential psychosexual late effects in both males and females.
The effect of radiation on tissues is in general progressive and may become symptomatic after a latent period, contrary to what tends to happen in cancer surgery. In the long term, excessive pelvic fibrosis may cause intestinal and urethral stenosis, lymphedema in the pelvis and of the lower extremities, endothelial damage, inflammation, ischemia, and necrosis in the retroperitoneal vessels and nerves [1].
Radiation dose to the pelvic organs is critical for acute bowel, bladder, and genital toxicity. Varying degrees of fibrotic changes and small vessel injury in and around the bladder and the prostate gland may reduce the bladder capacity and cause hematuria, ejaculatory dysfunction, and erectile dysfunction (ED) in men. Most of the data available on post-radiation ED come from studies in patients treated for prostate cancer. The etiology of ED in colorectal and bladder cancer patients is similar to that of patients treated for prostate cancer. No final conclusions can be drawn whether or not the radiation dose to the penile structures correlates with post-radiation ED in patients treated for prostate cancer [2]. Decrease in volume or the absence of semen is often associated with a deterioration of sexual activity in men.
In women, sexual dysfunction following pelvic radiation is associated with both multiple organic changes and psychological issues. After 6–12 months, vaginal atrophy and diminishing elasticity add to their experiencing lack of femininity and confidence. In the longer term, the atrophy can cause vaginal wall thinning, fibrosis, and adhesions, often followed by vaginal narrowing and shortening and ultimately even total vaginal stenosis. Temporary or permanent sterility occurs depending on the woman’s age at the time and dose of pelvic irradiation.
10.3 Examples from the Most Frequent Types of Pelvic Cancer
10.3.1 Prostate and Bladder Cancer
Prospective studies have shown an increase of ED between 1 and 2 years after radiotherapy, while ED rates did not seem to change after 3 years. Brachytherapy was originally introduced to limit the detrimental effects of external-beam radiotherapy (EBRT) on bowel and urinary function, and help preserve sexual function. Unfortunately, also after brachytherapy about half of the patients complain about ED.
The optimal treatment for patients with invasive bladder cancer is surgery. In women, an anterior exenterating is often performed, including the bladder, urethra, uterus, and the anterior vaginal wall, although the genitals can be spared. In men, a cystoprostatectomy is performed. Small local tumors can be treated with EBRT or brachytherapy in selected patients. Either treatment modality is associated with a high percentage of sexual dysfunction both in men and women.
10.3.2 Penile Cancer
Carcinoma of the penis is relatively rare, and accounts for about 1 % of all male cancers. The conventional treatment for penile cancer is partial or total penile amputation, or radiation. Radiation therapy provides good results in superficially infiltrating tumors, although it may have negative cosmetic and functional effects, resulting in psychosexual dysfunction.
10.3.3 Testicular Cancer
Germ cell tumors are relatively rare, accounting for about 1 % of all male cancers. Testicular malignancies can histopathologically be classified into seminomas, non-seminomas, and combined tumors. After the orchiectomy, seminomas are usually treated by radiotherapy to the para-aortic lymph nodes, whereas non-seminomas with nodal metastatic disease are treated by platinum-based chemotherapy.
Since the majority of patients undergo treatment during the most sexually active period of their lives, the impact of therapy on the quality of life in general, and on sexual functioning, fertility, and body image in particular, is very important. Self-report measures of sexual function conducted soon after treatment indicate high levels of dysfunction that tend to improve over time, in general 3–6 months after treatment. Limited research data on sexual functioning are available in long-term survivors of testicular seminoma treated with orchiectomy and radiotherapy. Following radiotherapy, a deterioration in sexual functioning has been reported in up to 25 % of the patients treated for testicular cancer [3]. More than half of testicular cancer patients report that their body image had changed after orchiectomy and radiotherapy.
10.3.4 Rectal and Anal Cancer
Radiation therapy has become an important part of the multimodality treatment of locally advanced rectal carcinomas and anal cancer. The addition of preoperative radiation for rectal cancer appears to increase the percentage of patients complaining of sexual dysfunction, both in males and in females. Women who undergo treatment for rectal cancer develop often severe sexual dysfunctions; adjuvant pelvic radiotherapy adds negatively to this risk. Both dyspareunia and vaginal dryness are reported by nearly 60 % of the women. Lack of lubrication, arousal problems, difficulties with orgasm, and loss of sexual spontaneity are very common sexual complaints. Women are often ashamed of their bodies and many are convinced of having lost their attractiveness for their partners. Compared with healthy controls, significant sexual dysfunction after treatment of anal cancer has been reported in both males and females.
10.3.5 Cervical Cancer
Early-stage cervical cancer is usually treated by surgery (radical hysterectomy and pelvic lymphadenectomy), whereas more advanced disease is treated with a combination of EBRT, brachytherapy, and concomitant chemotherapy. Patients identified with histologically high risk factors after surgery are given adjuvant EBRT and chemotherapy. Severe sexual dysfunctions are reported by patients compared to controls: narrowing and shortening of the vagina, persistent lubrication problems, often causing distress [4]. The effect of radiotherapy is progressive and persistent over time with no or little improvement to be expected. Significant psychological impairment such as feeling of guilt, self-blame, fear of recurrence, and anxiety are also often reported.
10.3.6 Endometrial Cancer
The majority of patients with endometrial cancer present themselves in stage I where surgery is the treatment of choice. Postoperative vaginal brachytherapy is equally effective in reducing the risk of loco-regional recurrence as EBRT but with fewer side effects. The most common complications include vaginal stenosis, vaginal vault scarring, vaginal adhesions, teleangiectasia (abnormally dilated capillary vessels), and mucosal atrophy. Only half of the women are sexually active after treatment.
10.4 Therapy of Male Post-Radiation Sexual Problems
Prior to the introduction of sildenafil, patients with prostate cancer complaining of post-radiation ED were treated with intracavernosal injections, a penile implant, or a vacuum device. With the availability of oral drugs to treat ED, these methods of therapy have lost popularity. The efficacy of sildenafil and tadalafil after radiotherapy for prostate cancer has been reported in about half of the patients. Similar results are reported after treatment of colorectal cancer.
10.5 Therapy of Female Post-Radiation Sexual Problems
Interventions for female sexual dysfunction relate to both acute and chronic effects of radiation on the vaginal wall and the vulva/perineum. However, attention should also be drawn to radiation-induced ovarian failure, which, in premenopausal women, may result in decreased vaginal lubrication and vulvo-vaginal atrophy and hence further aggravate the effect of radiation. Women with induced premature menopause report a significantly higher rate of hypoactive sexual disorders than their age-matched controls.
There is clear evidence that local and systemic estrogens have a significant positive effect on atrophic vaginitis, vaginal dryness, and dyspareunia in the healthy menopausal woman. As a means of preventing vaginal stenosis and treating established stenosis, a suggestion to resume sexual intercourse or to use a vaginal dilator together with lubricants is recommended after pelvic radiotherapy, especially if brachytherapy is applied. Unfortunately, compliance with the use of a vaginal dilator is usually low.
Conclusion
The prevalence of post-radiation sexual dysfunction is high both in men and women. Although vascular damage seems to play an important role in post-radiation ED and vaginal mucosal damage, a multifactorial etiology should instead be considered. Age, comorbidity, previous pelvic surgery, drugs, pretreatment sexual function, and hormonal treatment should be taken into account. A better understanding of the etiology would allow for more specific therapeutic modalities.
Sexual counseling is an important aspect. Patients need to be correctly informed on the pelvic anatomy and on the possible sequelae of radiation on their sexual life and functioning. It has been suggested that the great majority of oncology professionals are reluctant to address sexuality but also that the great majority of sexological professionals are unsure of cancer and its treatment effects.
References
1.
Andreyev J. Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients. Lancet Oncol. 2007;8:1007–17.CrossRefPubMed
2.
van der Wielen GJ, Mulhall JP, Incrocci L. Erectile dysfunction after radiotherapy for prostate cancer and radiation dose to the penile structures: a critical review. Radiother Oncol. 2007;84:107–13.CrossRefPubMed
3.
Wortel RC, Ghidey WA, Incrocci L. Orchiectomy and radiotherapy for stage I-II testicular seminoma: a prospective evaluation of short-term effects on body image and sexual function. J Sex Med. 2015;12:210–8.CrossRefPubMed
4.
Jensen P, Groenvold M, Klee M, et al. Longitudinal study of sexual function and vaginal changes after radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys. 2003;56:937–49.CrossRefPubMed