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Prostate Cancer Surgery and

Penile Shortening

Almost half of all patients  are unaware that they cannot have any ejaculation after prostate surgery for cancer. None of the Robotic prostate surgery (RP)  patients and only 10% of open RP patients recalled being informed of the potential for penile length loss (P < 0.01) and none were aware of the association between RP and Peyronie's disease.BJU Int. 2016 Oct;118(4):641-5.

Nearly 1 cm of penile shortening after RP may be expected up to 12 months. However, a trend toward recovery of penile length occurs after 24 months of follow-up and is completely re-established after 48 months. The preserved erectile function after RP is a predictor for penile length recovery. If erectile function is lost penile shortness is permanent. Urology. 2012 Dec;80(6):1293-6.

Penile shortening after radical prostatectomy peaks at the time of catheter removal and it continues to a lesser but still significant degree for at least 1 year. Nerve sparing surgery and recovery of erectile function appeared to have an independent protective effect on penile length loss at 1 year. These figures should be taken in consideration when counseling patients for radical prostatectomy. J Urol. 2007 Aug;178(2):602-7. Epub 2007 Jun 13. J Urol. 2013 Aug;190(2):592. doi: 10.1016/j.juro.2013.04.091. Epub 2013 May 1.The natural history of penile length after radical prostatectomy: a long-term prospective study.

 

A series of previously neglected sexually related side effects to radical prostatectomy (RP) has been identified over the recent years. These include orgasm‐associated incontinence (OAI), urinary incontinence in relation to sexual stimulation (UISS), altered perception of orgasm, orgasm‐associated pain (OAP), penile shortening (PS), and penile deformity. Frey, AU, Sønksen J, and Fode M. Neglected side effects after radical prostatectomy: A systematic review. J Sex Med 2014;11:374–385.A total of 43 articles were included. OAI and UISS are experienced by 20–93% of RP patients at least a few times after surgery. Although these issues are associated with postoperative daytime incontinence, previous transurethral resection of the prostate (TURP) is the only known predicting factor. Alterations of orgasmic function are experienced by approximately 80% after RP. Erectile dysfunction seems to play an important role in waning orgasmic function. Orgasm associated pain is only experienced by a subset of the patients with reported rates varying between 3% and 19%. Sparing of the tips of the seminal vesicles has been shown to double the risk of OAP. Penile shortening occurs in 15–68% of RP patients. Nerve sparing and preservation of erectile function may help preserve penile length. With regard to all side effects, studies indicate that they are reduced over time.

 

This is why it's essential, if men care at all about their future sex lives, they do everything possible to ensure erections of some mode (they are graded on a scale of 1-10 for hardness) occur before the 4th month after radical surgery. Why do erections need to occur? Because the absence of blood, and hence oxygen getting into the penis, leads to ongoing and progressive atrophy and tissue scarring.Dr Mulhall invokes the "use it lose it" saying here.

Apart from incontinence, the greatest risk that surgical patients face post-op is loss of erectile ability.The incipient damage is called "atrophy" which increases in probability the longer a patient goes without erection post-surgery. Atrophy is, in fact "a scarring of the erectile tissue, and if the erectile tissue scars, the patient will never get his own erection back and will always struggle with medication".

 

Dr. Mulhall goes on to note that "the incidence of erectile tissue damage, as measured by the presence of venous leak is very uncommon before the fourth month after surgery. However, at eight months after surgery it "occurs in about 30% of men and at one year 50% of men".

In this regard, he observes that a concerted effort at  "penile rehabilitation" is needed to help keep the erectile tissue healthy and "waiting for the nerves to recover from the trauma of surgery".

Dr. Mulhall notes the average healthy male gets 3-6 erections every night of his life, during sleep, but after surgery this isn't the case because of "nerve injury". He goes on to observe that the penile rehabilitation program aims to ensure or at least encourage, men to get at least 2-3 erections per week at a level of at least 6 (e.g. 6/10) on the hardness scale. He emphasizes that neither orgasm or penetration as in intercourse is required, just ensuring the erection, is enough to get blood and oxygen into the penis.

 

In a penile rehab program, the pre-op use of PDE5 inhibitors is implemented up to two weeks before surgery. The chemical pathways here include the cavernous nerves close to the prostate gland which secrete nitric oxide which stimulates release of an enzyme (cyclic GMP) inside the smooth muscle cells, promoting relaxation of smooth muscles and erection. An enzyme known as PDE5 prevents  prolonged erection. Hence, a PDE5 inhibitor such as Viagra suppress secretion the PDE5 enzyme and promotes erectile function 

 

Mulhall notes that the pre-op use of PDE5 inhibitors is a novel concept called "endothelial preconditioning, whereby the endothelium (the lining of the erection spaces) is in some way protected by pre-treatment. Typically, the patient then gets a prescription for a PDE5 inhibitor the day the Foley catheter is removed.  He is then "told to take a full dose of Viagra (100 mg) or Cialis (20 mg) once per week with adequate accompanying stimulation to attain at least a 6/10 erection. On the other 6 nights he's told to take a low dose pill (50 mg Viagra or 10 mg Levitra) before going to bed.

 

The aim throughout is to protect the erectile tissues from degeneration. If these rehab procedures don't work then more radical methods have to be considered such as: 1) penile injections, 2) intra-urethral suppositories, 3) vacuum devices, or 4) penile implants. None of these  are "enjoyable" but the alternative may be quite depressing and also pose latent health risks.

 

For example, Mulhall recommends a 29-gauge needle 1/2" in length for penile injection, and he provides a close-up diagrammatic view of where to inject on p. 145, noting the '10 o'clock'  position based on a frontal cross-section view.  He notes (ibid.): "You need to inject only one side of the penis to get an erection of the whole penis". The primary danger or side effect is possible priapism. The medications he recommends for injection are Trimix or Bimix. (The posture and positioning for injection is depicted on p. 142.)

 

BJUI Volume 110, Issue 10 November 2012  Pages 1491–1500

What's known on the subject? and What does the study add?

Penile shortening after total prostatectomy has been consistently reported, but most studies are small. BAUS has incorporated penile shortening into their patient information leaflets, but claims it is attributable to an anatomical alteration alone. No other organization even mentions penile shortening in their advice.

Our study shows that a true, and at least partially reversible, penile shortening occurs in a significant proportion of patients after total prostatectomy. The cause of the shortening is largely physiological and interlinked with the processes leading to erectile dysfunction.

 

Treatment for organ-confined prostate cancer includes the options of total prostatectomy (TP) and radiotherapy. Several complications are well documented for both treatments. The European Association of Urology (EAU) guidelines on prostate cancer [1] cite the following risks for TP: peri-operative death 0–2.1%, major bleeding 1–11.5%, rectal injury 0–5.4%, deep vein thrombosis 0–8.3%, pulmonary embolus 0.8–7.7%, lymphocoele 1–3%, urine leak from fistula 0.3–15.4%, slight stress incontinence 4–50%, severe stress incontinence 0–15.4%, impotence 29–100%, bladder neck obstruction 0.5–14.6%, ureteric obstruction 0–0.7% and urethral stricture 2–9%. Penile shortening is not mentioned in the EAU guidelines. The National Institute for Health and Clinical Excellence (NICE) guidance on prostate cancer [2] does not provide a comprehensive list of possible side effects, but focuses on sexual dysfunction and urinary incontinence; penile shortening is not mentioned. The BAUS patient information leaflets [3,4] on ‘radical retropubic prostatectomy’ and ‘robotic radical prostatectomy’ both mention an ‘occasional’ risk (defined as 2–10%) of ‘apparent shortening of the penis’.

 

With regard to late toxicity from radiotherapy, the EAU guidelines on prostate cancer [1] cite the following risks: cystitis 5.3%, haematuria 4.7%, urinary stricture 7.1%, urinary incontinence 5.3%, proctitis 8.2%, chronic diarrhoea 3.7%, small bowel obstruction 0.5%, leg oedema 1.5%, erectile dysfunction (ED) 55–76% and secondary malignancy 0.16%. Penile shortening is not mentioned. The NICE guidance on prostate cancer [2] does not provide a comprehensive list of possible side effects, but focuses on gastrointestinal side effects, sexual dysfunction and urinary incontinence; penile shortening is not mentioned. Patient information leaflets in our own trust also warn of further short- and long-term risks (in addition to the above): frequency, urgency, dysuria, bowel frequency and urgency, peri-anal soreness, tiredness, reduced libido and local hair loss. Again, penile shortening is not mentioned.

We performed literature searches using the EMBASE, MEDLINE, AHMED and PsycINFO databases up to October 2011 using the following keywords: prostat* and ‘penile length’/‘penile size’/‘penile shortening’ and ‘total prostatectomy’/‘radical prostatectomy’/‘retropubic prostatectomy’/‘laparoscopic prostatectomy’/‘robotic prostatectomy’ for articles relating to surgical treatment of prostate cancer, and prostat* and ‘penile length’/‘penile size’/‘penile shortening’ and radiotherapy for articles relating to radiotherapy for prostate cancer. We also looked at further references in the papers identified.

RESULTS

CURRENT EVIDENCE AFTER TP

There is now increasing evidence regarding penile shortening after TP, with most published studies pointing to a true shortening in a significant proportion of patients; however, different studies show significant variability in the details of surgery, the details of measurements, the amount of loss of length defined as clinically significant and many include only small numbers of patients. Details of the patient population studied in each of the 16 studies are shown in Table 1[5–20], the defined primary outcome, details of penile measurements as well as penile measurement outcomes are shown in Table 2[5–20], confounding factors and their analysis (where undertaken) are listed in Table 3[5–20], and possible explanations discussed by the authors are listed in Table 4[5–20].

 

 

CURRENT EVIDENCE AFTER RADIOTHERAPY

Only one article specifically related to radiotherapy: Haliloglu et al.[21] prospectively followed 47 patients with local or locally advanced prostate cancer who received androgen suppression plus radiotherapy and whose age ranged from 50 to 79 years. No patient had previous Peyronie's disease, or penile or urethral surgery. Stretched penile length (SPL) was measured by a single physician with a paper ruler from the tip of the glans to the pubopenile skin junction. The measurement was taken before treatment and every 3 months until 18 months. Mean SPL dropped from 14.2 cm pre-treatment to 8.6 cm at 18 months.

Zippe and Pahlajani (2008) [22] review information for post-surgical changes, but also mention their own unpublished data after prostate brachytherapy. Penile length and girth decreased ‘significantly’ during the first 6–12 months (no detailed data available).

HYPOTHESES OF PATHOPHYSIOLOGY

There are a number of theories as to the cause of penile shortening after TP, including loss of prostatic urethra, hypoxia of the corpora cavernosa, fibrosis and apoptosis of the corpora cavernosa, denervation/neuropraxia leading to apoptosis of the penile erectile tissue, sympathetic hyperinnervation, and physical lack of erections. Most of these hypotheses are interlinked.

The majority of evidence in this area comes from animal models, but some studies have been performed in patients after TP. McCullough [23] and Benson et al.[24] reviewed the evidence supporting various hypotheses for post-TP penile shortening.

 

Hypothesis 1: excision of prostatic urethra directly causes a reduction in penile length: Excision of prostatic urethra directly causing a reduction in penile length is the explanation given in the current BAUS patient information leaflets [3]. McCullough [23] and others argue that, were this hypothesis true, the erect penis would show signs of tethering (which is not observed). Benson et al.[24] point out that ‘the membranous urethra is fixed at the urogenital diaphragm and not easily retractable into the pelvic floor’, hence the bladder neck moves down rather than the urethra being pulled up.

Several studies, mentioned above, have measured not only penile length but also penile circumference and found both measurements to be reduced. The loss of the prostatic urethra cannot directly lead to reduced penile circumference. Savoie et al.[8], Gontero (2007) [13] and Engel et al.[19] assessed whether any correlation existed with prostate size (and hence length of urethra removed), and found no difference. In addition, various animal studies have shown decreases in penile dimensions by unilateral or bilateral denervation alone, without removal of any part of the urethra. It is therefore necessary to look for other explanations.

 

Hypothesis 2: denervation, and equally neuropraxia, cause lack of erections, which causes penile hypoxia. Denervation and neuropraxia also cause atrophy and apoptosis of the corporal smooth muscle. Together, these result in corporal fibrosis and a reduction in penile dimensions: Several groups have shown that loss of penile length is closely related to the presence and severity of ED. McCullough [23] points out that ‘nocturnal erections are believed to be important in preserving the structural and functional integrity of the penis’. Nocturnal penile tumescence is virtually eliminated after surgery, but improves over time. Nightly sildenafil improves recovery of nocturnal tumescence.

 

Yuan et al.[25] report on a randomized study in rats comparing (i) sham surgery, (ii) bilateral cavernous nerve crushing, and (iii) bilateral cavernous nerve crushing + vacuum erection device treatment (5 min daily from 10 days after surgery). Penile shrinkage occurred in group 2, but not group 3. Rats in group 2 had evidence of higher hypoxic and apoptotic markers and increased collagen disorganization compared with group 3 at 4 weeks after surgery.

 

Moreland et al.[26], in their human study, and Leungwattanakij et al.[27], in a rat study, showed that the flaccid denervated penis is relatively hypoxic. During a prolonged period without any erections, the hypoxia results in remodelling and corporal fibrosis. Klein et al.[28] and User et al.[29] showed biochemical and morphological changes in the denervated corpora of rats, consistent with increased apoptotic activity, and loss of penile weight and size. The changes were more significant if denervation was bilateral. Apoptosis was most prominent in the smooth muscle just beneath the tunica albuginea. Fibrosis of the corpora explains the higher incidence of Peyronie's disease after TP.

 

Ciancio and Kim [6], Schwartz et al.[30] and Iacono et al.[31] showed progressive fibrosis in the corpora cavernosa of men after TP, sometimes similar to primary changes in Peyronie's disease. Fibrosis, curvatures and smooth muscle content improved with sildenafil or ‘treatment for Peyronie's disease’.

 

Hypothesis 3: acute neuronal injury or denervation causes sympathetic overdrive or hyperinnervation and a hypertonic retracted penis: Benson et al.[24] explain that acute neuronal injury may result in sympathetic overdrive or in hyperinnervation owing to faster regeneration of sympathetic fibres compared with parasympathetic fibres, resulting in a hypertonic retracted penis in the early phase (lasting days or weeks). Whilst this cannot explain longer term changes on its own, it may be part of a multitude of factors leading to penile shortening.

Hypothesis 4: direct irradiation of the penile base causes a reduction in penile length: Vijayakumar et al.[32] showed that three different radiotherapy techniques (axial coplanar four-field box technique, six-field coplanar technique, and coplanar non-axial four-field technique) result in measurably different doses of radiation delivered to ‘penile structures’ and postulate that this may affect post-treatment sexual function.

Weil et al.[33] evaluated a further radiotherapy technique (three-field arc technique), showing minimal toxicity to the base of the penis.

Perna et al.[34] compared MRI and CT in defining the prostatic apex, and subsequently evaluated the ability to spare the penile bulb using three-dimensional conformal radiation therapy, Linac-intensity-modulated radiation therapy or helical tomography. Again, the assumption was that avoiding direct radiation of the penile bulb would preserve more sexual function.

 

Any radiation toxicity is likely to result from damage to vascular and connective tissue rather than nerve cells, as nerve cells are more resistant to radiation damage. The mechanism would therefore be expected to be different from that causing penile shortening after TP. However, no study has examined the relationship of the radiotherapy technique or dose to the presence or severity of penile shortening; neither has the pathophysiology been examined.

PSYCHOLOGICAL ASPECTS AND CONSENT ISSUES

There is significantly less evidence in the area of psychological aspects to penile shortening or consent issues, but we identified three articles addressing these factors.

Yu Ko et al.[35] specifically looked at men's responses to experiencing penile shortening. This was a qualitative study of six patients who had had TP at least 1 year before semi-structured interviews were performed. The main findings were those of resignation and acceptance, unaltered sense of masculinity, and relative unimportance of penile shortening. Notably, all six men interviewed had significant ED; and they stated that the return of erectile function would be ‘the single event that would improve satisfaction with penile function’. Penile length was seen as relatively insignificant when intercourse was not possible for other reasons.

 

Deveci et al.[36] questioned 336 consecutive patients, within 3 months of their TP, regarding sexual function information given before surgery. They found that men's expectations were ‘largely unrealistic’. Only 10% of 216 patients who underwent open TP and none of 120 patients who underwent robotic TP were aware of possible penile length changes.

 

Sun [37] reports on their regime of penile rehabilitation, stressing not only the importance of sex therapy postoperatively and patient choice in the method of penile rehabilitation, but also arguing strongly for better preoperative counselling to include the psychosexual complications of TP. He found that couples accepted penile rehabilitation as part of their holistic treatment, ‘even if they are not so active in their sexual lives’.

DISCUSSION

McCullough [23] summarizes: ‘To say that men are obsessed with their penile measurements from early adolescence on is an understatement.’ In spite of whatever psychological changes a man goes through after his prostate cancer diagnosis, this statement sums up why it is important to inform men about the risk of penile shortening after TP and perhaps even after radiotherapy at the time when treatment decisions are made.

 

Penile measurements and functioning are a quality-of-life issue and, as such, they are important considerations in men receiving treatment for organ-confined prostate cancer. Many of these patients will be in their 50s and 60s when sexual functioning is important for most men's perception of quality of life. As Yu Ko et al.[35] have shown, men will adapt to their new situation, but we must strive to preserve or re-establish as much normal sexual functioning as is possible as part of holistic cancer treatment.

As shown in Tables 1–3[5–20], there is significant variation between different studies relating to preoperative function and comorbidities, type of operation used, penile rehabilitation postoperatively and details of how measurements were taken. Some authors included all patients undergoing TP (e.g. Savoie et al.[8]), others selected only the fittest and youngest sexually active patients with the lowest stage cancers and the least radical surgery into their study (e.g. Briganti et al.[14]). It is thus unsurprising that results vary. Many of the studies are small (more than half reported on ≤65 patients) and not one reports a power calculation for penile size measurements. Carlsson et al.[20] should be commended on assessing 1288 patients and 350 population-based controls, but this was done by a single question (‘Is your penis shorter compared with when you were 30 years old?’), which is not only subjective, but also fails to focus specifically on the impact of the operation. Briganti et al.[14] confirm the importance of objective measurements, as these were unchanged in all patients, despite nine of 33 patients reporting subjective penile shortening.

 

The most common measurement used is SPL, which is considered comparable to erect length. The proximal point of reference is the pubopenile skin junction or the pubic bone. The distal point of reference is the tip of the glans, the meatus or the coronal sulcus. Consequently, direct comparisons can be difficult. The most frequently adopted method is that described by Munding et al.[7] of a paper ruler measurement (to the nearest 0.5 cm) from the pubopenile skin junction to the tip of the glans. Interestingly, no study found differences in erect penile dimensions or penile circumference without differences in SPL, suggesting that measurement of SPL is sufficient.

 

Gontero et al.[13] present an enlightening diagram of the spread of their measurements at each timepoint: SPL ranges from 6 to 21 cm before surgery and 5 to 19 cm at 18 months, illustrating that comparisons of means or medians may be of little value. Most authors measured to the nearest 0.5 cm, which appears clinically sensible, but it should follow that only changes ≥1 cm can be considered true changes; however, few draw this conclusion and instead report any change without regard for clinical relevance. Gontero et al.[13] proceed to report mean values to the nearest 0.01 cm, despite having initially measured to the nearest 0.5 cm. Some authors report changes in mean values, some report individual changes, some percentage changes, and some absolute changes. Measurements were most commonly taken by a single person, but not infrequently by the operating surgeon, which may introduce bias. The only long-term study was reported by Vasconcelos et al.[18], who observed 105 patients over 5 years. Mean SPL initially decreased, but returned to baseline at 4 years, remaining stable to 5 years. As the changes in mean SPL were small, the difference was not statistically significant at any timepoint.

We advise explicit mentioning of penile shortening in the consent process for TP and potentially also for radiotherapy for prostate cancer. We also advise early penile rehabilitation to improve the patient's own body image and, with that, quality of life, even in patients who do not seek treatment specifically for ED. The choice of method of penile rehabilitation should be left to the patient.Any future studies need to use an agreed unified method and we suggest the measurement reported by Munding et al.[7], with analyses focusing on individual changes, considering differences of ≥1 cm as true changes. The measurements should be taken by a single person, who is not otherwise involved in the treatment of the patients.

 

Studies specifically in radiotherapy are very limited currently and no clear conclusions can be drawn. Regarding TP, it is possible that each of the hypotheses above plays some part in the overall process leading to reduced penile dimensions. It seems unlikely, however, that the loss of urethral length plays a significant role (level of evidence 3). It is likely that the mechanism is at least linked to that causing ED, if not the same mechanism. Several, but not all, studies have shown a better outcome with diligent nerve-sparing and early penile rehabilitation for all treatment methods. Clear biochemical and histological changes (hypoxia, fibrosis, apoptosis) have been shown in rat models and human studies. Some of the rat studies are randomized controlled trials of various degrees of cavernosal nerve damage (level of evidence 1b), but total numbers are small (≤30 per study). All of the human trials were observational (level of evidence 3). The hypothesis of sympathetic hyperinnervation is based on experimental evidence assessing the effects of cardiac autonomic nervous injury in dogs. Although quoted repeatedly, there are no studies specifically assessing this hypothesis in penile tissues (level of evidence 4).

 

There is continued uncertainty of whether and how penile length changes are preventable or reversible, and which is the best strategy. As length changes appear linked to ED, it does seem prudent to commence penile rehabilitation early, regardless of the specific treatment chosen.

 

BJU Int 2014; 113: E131–E136 Even with a rigorous protocol of rehab 5%of men had penile shotening over half an inch after surgery

A regimen of daily PDE5i use predicted preservation of SFPL at the 6-month timepoint. Patients should be counselled as to the risks and natural history of penile length loss before undergoing RP.

Penile fibrotic changes have been observed in 41% of men with ED after RP, leading to decreased elasticity and probably decreased stretched length [21].  

In addition, two studies have looked at the use of a vacuum erection device (VED) and its effect on stretched penile length in patients after RP. In one study, 39 men had pre- and postoperative measurements of penile length, with VED use initiated the day after catheter removal and continued for 90 days [14] At the last follow-up (mean 9.5 months), 12% of the early intervention group had a >2-cm loss, compared with 45% in the late group

 

Mean SFPL length loss is reported in three of these studies [7,8,10], with results varying from no mean loss at 6 months [8] to 2-cm loss at 1-year follow-up [7].

7 J Urol 2007; 178: 602–7 14Int J Impot Res 2007; 19: 501–4 10. Urology 2012; 80: 1293–6 .21 BJU Int 2000; 85: 101–6 8Eur Urol 2007; 52: 702–7

Having been the victim of this subject, I have done a lot of reading about it both from men having gone through it and various research about it by the medical industry. I am beginning to be disgusted by articles debating whether or not it happens - usually hosted by some medical institution. IT HAPPENS! FACT! Research WHY it happens and fix it, not IF it happens! The medical field's take on this seems to be that if you tell a lie long enough people will believe it. Muddy the one fact with enough "research trivia" and the fact will be discredited. Maybe this side effect is not avoidable - then be honest and admit it, don't try to cover it up or skirt the subject. We are men, we can take the truth, even if it not what we want to hear. This is a minor affliction as is viewed by the medical community but we men see that it causes major issues with self esteem which we must keep to ourselves because it is deemed silly to be so effected by this. JR

 

After nearly a year had passed , I started to have functional erections with the help of a prescription PDE5 inhibitor. My post surgical erections were noticably smaller my normal erections but I assumed the smaller size was the early phase of a gradual progression toward an approximate restoration of normal erections , i.e., a correlation between firmness and size. Unfortunately - and surprisingly - this was not to be the case. In fact, I was unprepared, and ill advised, for the smaller length and girth of my post-op erections.

Complaints about a reduced penile size were more common with RT plus ADT or surgery than RT alone and were associated with greater interference with close emotional relationships and increased treatment regret. Physicians should discuss the possibility of this rarely mentioned side effect with their patients to help them make more informed treatment choices.Urology. 2013 Jan; 81(1): 130–134.