Erectile dysfunction (ED) is one of the major but underreported concerns in cancer patients and survivors. It can lead to depression, lack of intimacy between the couple, and impaired quality of life. The causes of erectile dysfunction are psychological distress and endocrinal dysfunction caused by cancer itself or side effect of anticancer treatment like surgery, radiotherapy, chemotherapy and hormonal therapy. The degree of ED depends on age, pre-cancer or pre-treatment potency level, comorbidities, type of cancer and its treatment. Treatment options available for ED are various pharmacotherapies, mechanical devices, penile implants, or reconstructive surgeries. A complete evaluation of sexual functioning should be done before starting anticancer therapy. Management should be individualized and couple counseling should be an integral part of the anticancer treatment.
Cancer diagnosis and its management lead to physical and emotional distress in patients. Sexual dysfunction is one of the common problems encountered in these patients which can occur due to direct or indirect pathways. Sexual dysfunction can be in the form of erectile dysfunction (ED) and ejaculatory dysfunction such as decreased or absent semen. Chemotherapy, radiation, hormonal therapy and surgery all can lead to erectile dysfunction. ED has been widely described after prostate cancer treatment. Incidence of post-treatment ED in prostate cancer can vary from 24% (brachytherapy alone), 40% (brachytherapy plus external beam radiotherapy [EBRT]), 45% (EBRT alone), 66% (nerve-sparing radical prostatectomy [RP]), 75% (non-nerve sparing RP), and 87% for cryosurgery [
Besides disease control, restoration of quality of life (QoL) is also very important due to increase number of cancer survivors. Evaluating ED using valid questionnaires and management of ED is one of the important aspects of QoL which is particularly important in developing countries where people are not comfortable discussing about their sexual issues. Age and degree of ED before the diagnosis and mode of treatment play an important role in predicting the post-treatment ED. For this review, we searched PubMed data using words “cancer related erectile dysfunction”, “erectile dysfunction in cancer”, “sexual dysfunction in genitourinary malignancies,” and “psychosocial outcome of cancer survivors”. All studies reporting erectile dysfunction in cancer patients and survivors were reviewed. Around 60 studies were screened and data from 54 studies that reported sexual dysfunction or erectile dysfunction in cancer was included in the review.
The loss of erectile ability leads to depressive symptoms, lack of sexual satisfaction and general happiness in life. Men who fail to achieve erection tend to lose confidence [
Blood supply to the penis occurs via branches of external and internal pudendal arteries. Penile innervations are derived from pudendal and cavernous nerves. Pudendal nerve is responsible for somatic motor and sensory nerve supply. Cavernous nerve is a part of autonomic nervous systems and includes sympathetic and parasympathetic fibres. It runs in crus and corpora of the penis and regulates the blood flow during erection and flaccid state [
An erection begins with sensory and mental stimulation. Sexual arousal leads to relaxation of smooth muscles of the penile arteries which increases the blood flow to penis. This leads to rigidity and thus erection of the penis. While returning to flaccid state, penile muscles contract and increase the venous outflow and decrease the length and girth of the penis. The ability to attain and sustain erection depends on integrity of vascular supply and nerve supply.
Causes of ED in cancer patient are follows: (1) emotional, physical and financial stress; (2) pain, anxiety and disturbed body image; (3) damage to penile nerve and vessels during surgery, radiotherapy (RT) and chemotherapy; (4) ADT; (5) penectomy for cancer penis; Nitric oxide (NO) pathway plays an important role in achieving erection. NO is the principle agent responsible for relaxation of penile smooth muscles and thus erection. Radiation leads to damage and inflammation of cavernous nerves, leading to decreased production of nitric oxide synthase and NO which subsequently leads to ED [
Prostate cancer is one of the most common cancers in males worldwide. Due to widespread use of prostate-specific antigen (PSA), increased numbers of young and healthy men are diagnosed with prostate cancer as compared to past. RP leads to excellent survival and is one of the established treatments for early stage prostate cancer. With excellent disease control, potential side effects of surgery are a growing concern out of which ED is one of the important focuses [
ED can be commonly seen after surgery for bladder cancer. Zippe et al. [
Perception of reduced penile length has been seen after RP and RC. Loh-Doyle et al. [
Testicular cancer is commonly seen in young patients and thus determining sexual function is even more important. After treatment of testicular cancer, 12%–40% of patients can have ED due to hormonal imbalance including low testosterone, orchidectomy or retroperitoneal lymph node dissection [
Colorectal cancer (CRC) is another common malignancy in males. Surgery for these cancers may also impair sexual function due to hypogastric and autonomic nerve injury [
Radiotherapy-induced erectile dysfunction (RIED) occurs due to higher dose to penile bulb, crura and neurovascular bundle especially in bladder and prostate cancer. Incidence of RIED has been mentioned above. RIED generally take over 1 year to develop, gradually increases and becomes constant after 3 years [
Till date, there is no definite data to suggest the co-relation of RT dose and ED. Relating ED to RT alone is difficult as multiple other factors also contribute to ED like smoking, diabetes mellitus, hypertension, concomitant treatment, etc. Earlier in a study by RTOG group, Roach et al. [
Few studies have observed that ED and penile bulb dose show a dose volume relationship. Fisch et al. [
QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic) has defined that penile bulb may not be a critical structure for ED but may act as surrogate for yet to identified critical structures for ED and suggested a mean dose of not more than 50 Gy to 95% volume of penile bulb. In a recently published preliminary patient reported outcomes in RTOG 0126 trial, at 2 years, no significant difference in sexual function was reported in 3DCRT (high penile bulb dose) or IMRT (lower penile bulb dose) arm [
Based on the patient reported outcomes, Thor et al. [
Chemotherapy and hormone therapy also play a role in ED. Several chemotherapeutic agents are known to cause ED by causing neural and vasculature damage. These are mainly cisplatin, vincristin and vinblastin. Wiechno et al. [
ADT is commonly used in the treatment of prostate cancer which is known to cause lack of sexual interest. Loss of libido usually develops within the first several months, and ED follows. In one study sexual inactivity started 6 months after starting ADT [
Age of patient and his sexual partner is one of the most important factors while deciding the treatment plan.
Phosphodiesterase-5 inhibitors (PDE-5i)/sildenafil citrate (Viagra) is highly an effective and most commonly used oral agent as a first line therapy used in clinical practice [
Alprostadil (synthetic form of prostaglandin E1 [PGE1]), phentolamine (vasodilator) or papaverine (smooth muscle dilator) can be used for intracavernosal injection [
Alprostadil (MUSE) suppository is inserted in urethra via a small applicator. It creates a vaso-dilatory effect on penile blood vessels and thus helps in penile erection [
It is a battery powered device and can be used in conjunction with a PDE-5i to help maintain and sustain an erection. It consists of cylinder with a pump and constriction ring. Cylinder and pump create vacuum that helps in penile erection while constriction ring helps in maintain erection. Although it is an inexpensive approach, mechanical failure is a problem. Other problems with this device are infection and penile discomfort.
Inflatable or non-inflatable penile implants is an effective safe and durable treatment option for ED and are generally used once patient becomes refractory to other treatment options. In one study it was reported that only <5% men underwent penile implantation after RP [
Vascular reconstruction in the form of arterial vascularisation, venous arterialization or venous stripping improves blood flow to corpora cavernosa and thus helps in achieving and maintaining erection [
It is a non-invasive newer technology for the treatment of ED. It acts by inducing localized angiogenesis, and pushing blood to the penis [
Cancer diagnosis and its treatment can lead to variable degree of sexual dysfunction in patients ranging from loss of libido to complete loss of erection. As sexual issue is a generally less discussed topic, ED is one of the underreported issues in cancer patients. ED can lead to depression and impaired quality of life. Thus, it is very important to evaluate ED before and after treatment. For men who have ED or in those when ED is predictable, couple counselling should be an essential component of the cancer management. Method of sexual rehabilitation should be individualised for each patient.
No potential conflict of interest relevant to this article was reported.
Erectile dysfunction in cancer (original)
S. No. | Study | Year | No. of patients | Age (yr) | Primary tumor | Treatment modality (% of patients) | RT dose (Gy) | Probability of sexual function preservation | Incidence of ED | Remarks |
---|---|---|---|---|---|---|---|---|---|---|
1 | Mullins et al. [ |
2019 | 835 | 63.7 (mean) | Prostate | EBRT (23%) | - | EBRT (14%–70%) | - | RT alone results in the best preservation of sexual function |
Brachytherapy (15%) | Brachytherapy (14%–70%) | |||||||||
EBRT + ADT (12%) | EBRT + ADT (8%–52%) | |||||||||
RP + NS (41%) | RP + NS (4.7%–45.3%) | |||||||||
RP + non-NS (10%) | RP + non-NS (5%–34%) | |||||||||
2 | Resnick et al. [ |
2013 | 1655 | 55–94 | Prostate | Prostatectomy (70.3%) | - | - | Prostatectomy (46.7%) | Patients underwent prostatectomy were more likely to have erectile dysfunction at 2 years and 5 years |
EBRT (29.6%) | EBRT (39.7%) | |||||||||
3 | Hekal et al. [ |
2011 | 45 | 31–64 | Urinary bladder | RC + NS (46.6%) | - | RC + NS (spontaneous erection, 57.8%) | RC + NS (42.2%) | Gradual progressive improvement was observed in vasogenic competence in NS cases |
RC + non-NS (53.4%) | RC + non-NS (no spontaneous erection) | RC + non-NS (100%) | ||||||||
4 | Zippe et al. [ |
2004 | 49 | 57.8 (mean) | Urinary bladder | RC + NS (33%) | - | RC + NS (spontaneous erection, 50%) | RC + NS (50%) | - |
RC + non-NS (67%) | RC + non-NS (spontaneous erection, 3%) | RC + non-NS (97%) | ||||||||
5 | Loh-Doyle et al. [ |
2020 | 151 | 66.1 (median) | Urinary bladder | RC (100%) | - | - | Loss of penile length, ≥2.54 cm (55.1%) | RC can result in significant sexual dysfunction, as the significant loss in penile length |
6 | Tal et al. [ |
2014 | 76 | 29 (mean) | Testicular cancer | Orchiectomy (100%) | - | - | Loss of ability to maintain erection (84%) | ED after treatment appear to have normal erectile haemodynamics on penile duplex Doppler and all responded to treatment |
EBRT (26.3%) | ||||||||||
Chemotherapy (47.3%) | ||||||||||
RPLND (19.7%) | ||||||||||
7 | Capogrosso et al. [ |
2016 | 143 | 42 (median) | Testicular cancer | Orchiectomy (100%) | 20–24 | - | 24.5% | Adjuvant therapy was not associated with impaired recovery of normal sexuality |
EBRT (32.9%) | ||||||||||
Chemotherapy (81.8%) | ||||||||||
RPLND (42.8%) | ||||||||||
8 | Duran et al. [ |
2015 | 56 | 27–79 | Rectum | APR (19.6%) | - | - | 21.8% | Lower 1/3 of tumor location, age younger than 60 years, RT, and stoma were risk factors for ED |
LAR (80.4%) | ||||||||||
RT (80.4%) | ||||||||||
9 | Pokharel et al. [ |
2019 | 26 | 26–75 | Colorectal | NACRT (100%) | - | Sexual desire (57.7%) | ED (42.3%) | - |
APR (7.6%) | Not able to attain erection (38.4%) | |||||||||
LAR (92.3%) | Unable to ejaculate (34.6%) | |||||||||
10 | van der Wielen et al. [ |
2007 | 268 | 68 (median) | Prostate | EBRT; standard vs. dose escalation | 68 vs. 78 | Sexual desire (41%) | 38% | In sexual function, no significant differences were found between the two dose-arms |
3DCRT in both arms | ||||||||||
11 | Pinkawa et al. [ |
2011 | 156 | 55–83 | Prostate | EBRT (3DCRT vs. IMRT) | 70 vs. 76 | Patients with erections firm enough for sexual intercourse; 32% vs. 65% | 86% vs. 70% | Dose escalation with IMRT is not associated with increased sexual morbidity |
12 | Mangar et al. [ |
2006 | 51 | 47–78 | Prostate | EBRT; standard vs. dose escalation | 64 vs. 74 | Remained potent (23.5%) | 78% | Penile bulb dose; D90 > 50 Gy significant risk of erectile dysfunction |
Conformal RT | Reduced potency (43.1%) | |||||||||
Impotent (33.3%) | ||||||||||
13 | Fisch et al. [ |
2001 | 21 | 72 (mean) | Prostate | EBRT; 3DCRT | 67.3–87.3 | Remained potent (38%) | 62% | 70 Gy to more than 70% volume of penile bulb, high risk of ED |
Reduced potency (38%) | ||||||||||
Impotent (24%) | ||||||||||
14 | Bruner et al. [ |
2015 | 1006 | 50–88 | Prostate | EBRT (3DCRT vs. IMRT) | 79.2 vs. 79.2 | No statistically significance differences were observed between two groups in erectile function scores | - | Penile bulb dose does not correlate with ED |
15 | Thor et al. [ |
2015 | 501 | - | Prostate | EBRT; | 70 | Suggested that presence of naturally occurring erections were crucial for erectile and orgasmic function | 41% | Strong association found between ED and doses to total penile structure than penile bulb |
3DCRT (60.2%) | ||||||||||
RP + 3DCRT (39.8) | ||||||||||
16 | Zelefsky et al. [ |
2006 | 561 | ≥60 | Prostate | EBRT; | 81 | Sexual desire (51%) | ADT +IMRT (57%) | Addition of short-term ADT significantly increased the risk of ED in these patients |
ADT + IMRT vs. IMRT | IMRT alone (43%) | |||||||||
17 | Pinkawa et al. [ |
2009 | 123 | 53–84 | Prostate | EBRT ± PDE-5i | 70.2–72 | Ability to have an erection (70%) | 30% | Age and diabetes are risk factors for post EBRT ED |
Erections firm enough for sexual intercourse (53%) |
RT, radiotherapy; ED, erectile dysfunction; EBRT, external beam radiotherapy; ADT, androgen deprivation therapy; RP, radical prostatectomy; NS, nerve sparing; RC, radical cystectomy; RPLND, retroperitoneal lymph node dissection; APR, abdominoperineal resection; LAR, low anterior resection; NACRT, neoadjuvant chemoradiotherapy; 3DCRT, three-dimensional conformal radiotherapy; IMRT, intensity-modulated radiotherapy; PDE-5i, phosphodiesterase 5 inhibitors.