Page 47 - Remedial Andrology

5.3.1 Pelvic surgery and prostate cancer treatment
Pelvic surgery, especially for oncological disease (e.g., radical prostatectomy (RP) [357] or radical cystectomy
[358] and colorectal surgery [359]), may have a negative impact on erectile function and overall sexual
health. The most relevant causal factor is a lesion occurring in the neurovascular bundles that control the
complex mechanism of the cavernous erectile response, whose preservation (either partial or complete) during
surgery eventually configures the so-called nerve-sparing (NS) approach [360]. Therefore, surgery resulting in
damage of the neurovascular bundles, results in ED, although NS approaches have been adopted over the
last few decades. This approach is applicable to all types of surgery that are potentially harmful to erectile
function, although to date, only the surgical treatment of PCa has enough scientific evidence supporting its
potential pathophysiological association with ED [361-363]. However, even non-surgical treatments of PCa (i.e.,
radiotherapy, or brachytherapy) can be associated with ED [364, 365]. The concept of active surveillance for the
treatment of PCa was developed to avoid over-treatment of non-significant localised low-risk diseases, while
limiting potential functional adverse effects (including ED). However, it is interesting that data suggest that even
active surveillance has a detrimental impact on erectile function (and sexual well-being as a whole) [366-368].

To date, some of the most robust data on PROMs including erectile function, comparing treatments for
clinically localised PCa come from the Prostate Testing for Cancer and Treatment (ProtecT) trial, in which 1,643
patients were randomised to active treatment (either RP or RT) and active monitoring and were followed-up
for 6 years [369]. Sexual function, including erectile function, and the effect of sexual function on QoL were
assessed with the Expanded Prostate Cancer Index Composite with 26 items (EPIC-26) instrument [370, 371].
At baseline, 67% of men reported erections firm enough for sexual intercourse but this fell to 52% in the active
monitoring group, 22% in the RT group, and 12% in the RP group, at 6-months’ assessment. The worst trend
over time was recorded in the RP group (with 21% erections firm enough for intercourse after 3 years vs. 17%
after 6 years). In the RT group, the percentage of men reporting erections firm enough for intercourse increased
between 6 and 12 months, with a subsequent decrease to 27% at 6-years assessment. The percentage
declined over time on a yearly basis in the active monitoring group, with 41% of men reporting erections firm
enough for intercourse at 3 years and 30% at 6 year evaluations [369].

Radical prostatectomy (open, laparoscopic or robot-assisted) is a widely performed procedure with a curative
intent for patients presenting with clinically localised intermediate- or high-risk PCa and a life expectancy of >
10 years based on health status and co-morbidity [372, 373]. This procedure may lead to treatment-specific
sequelae affecting health-related QoL. Men undergoing RP (any technique) should be adequately informed
before the operation that there is a significant risk of sexual changes other than ED, including decreased libido,
changes in orgasm, anejaculation, Peyronie’s-like disease, and changes in penile length [363, 365]. These
outcomes have become increasingly important with the more frequent diagnosis of PCa in both younger and
older men [374-376]. Research has shown that 25-75% of men experience post-RP ED [377], even though
these findings had methodological flaws; in particular, the heterogeneity of reporting and assessment of ED
among the studies [361, 378]. Conversely, the rate of unassisted post-operative erectile function recovery
ranged between 20 and 25% in most studies. These rates have not substantially improved or changed over
the past 17 years, despite growing attention to post-surgical rehabilitation protocols and refinement of surgical
techniques [378-380].

Overall, patient age, baseline erectile function and surgical volume, with the consequent ability to preserve the
neurovascular bundles, seem to be the main factors in promoting the highest rates of post-operative potency
[362, 375, 377, 381]. Patients being considered for nerve-sparing RP (NSRP) should ideally be potent pre-
operatively [374, 375]. The recovery time following surgery is of clinical importance in terms of post-operative
recovery of erectile function. Available data confirm that post-operative erectile function recovery can occur up
to 48 months after RP [382]. Likewise, it has been suggested that post-operative therapy (any type) should be
commenced as soon as possible after the surgical procedure [374, 377], although evidence suggests that the
number of patients reporting return of spontaneous erectile function has not increased.

In terms of the effects of surgical interventions (e.g., robot-assisted RP [RARP] vs. other types of surgery), data
are still conflicting. An early systematic review showed a significant advantage in favour of RARP in comparison
with open retropubic RP in terms of 12-month potency rates [383], without significant differences between
laparoscopic RP and RARP. Some recent reports confirm that the probability of erectile function recovery is
about twice as high for RARP compared with open RP [384]. More recently, a prospective, controlled, non-
randomised trial of patients undergoing RP in 14 Swedish centres comparing RARP versus open retropubic
RP, showed a small improvement in erectile function after RARP [385]. Conversely, a randomised controlled
phase 3 study of men assigned to open RP or RARP showed that the two techniques yielded similar functional
outcomes at 12 weeks [386]. More controlled prospective well-designed studies, with longer follow-up, are

46 SEXUAL AND REPRODUCTIVE HEALTH - MARCH 2021