ISSN: 2047-2919 ANDROLOGY

ORIGINAL ARTICLE

Correspondence:
Rahul Krishnan, Male Sexual and Reproductive Erectile function recovery in
Medicine Program, Sidney Kimmel Center for
Prostate and Urologic Cancers, Memorial Sloan- patients after non-nerve sparing
Kettering Cancer Center, 353 East 68th Street,
New York, NY 10065, USA. radical prostatectomy
E-mail: rak2022@med.cornell.edu

Keywords:
erectile dysfunction, erectile function, non-nerve
sparing, prostate cancer, radical prostatectomy
1
R. Krishnan, 1D. Katz, 2C. J. Nelson and 1J. P. Mulhall
1
Division of Urology, Sexual and Reproductive Medicine Program, Memorial Sloan-Kettering Cancer
Center, and 2Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer
Center, New York, NY, USA

Received: 22-Jun-2014
Accepted: 3-Sep-2014

doi: 10.1111/andr.282

SUMMARY
Few studies have looked at erectile function recovery (EFR) rates in men undergoing non-nerve sparing resection during radical
prostatectomy (RP). Existing studies show great variation in EFR rates owing to multiple factors that minimize their utility in counsel-
ling RP patients. We investigated the EFR rate and its predictors in unilateral cavernous nerve resection and bilateral cavernous nerve
resection patients 24 months after RP. We conducted a population-based, prospective cohort study of 966 patients who underwent
RP at a tertiary cancer centre from 2008 to 2012. Cavernous nerve condition was evaluated on a 4-point nerve sparing score and
assigned to one of three groups: bilateral sparing, unilateral resection (UNR) and bilateral nerve resection (BNR). EF was assessed
pre-RP and 24–30 months post-op using a validated 5-point patient-reported scale (1 = fully rigid; 5 = no tumescence). EFR was
defined as a post-op EF grade of 1–2. Statistical analysis included descriptive statistics, ANOVA, chi-square, Fisher’s exact test and logis-
tic regression. Mean baseline EF was 1.84  1.3 and 2.74  1.5 for UNR and BNR patients respectively. Thirty-three percent of UNR
patients and 13% of BNR patients exhibited EFR. Age, baseline EF were predictors of EFR. Multivariable analysis showed baseline EF
was a significant predictor of EFR at 24 months for UNR. For BNR patients, pre-RP EF was the only factor predictive of EFR. Patients
undergoing nerve resection still have a significant chance of achieving true EFR, with UNR surgery patients showing more potential
for improvement than patients undergoing BNR surgery. Age and baseline EFR characterize recovery prospects in these two groups.
Physicians should thus measure and account for baseline EF in addition to age and the degree of nerve resection when advising
patients about expectations for successful EF following RP.

INTRODUCTION recovery (EFR). Despite this, few studies to date have

In 2013, approximately 238 590 new cases of prostate cancer
(PCa) were diagnosed in the United States, accounting for 28%
of all incident cancer cases among men (Siegel et al., 2013). Rad-
ical prostatectomy (RP) has been established as a curative treat-
ment for men with early stage PCa and is associated with a
reduced rate of death in patients for years after surgery (Bill-
Axelson et al., 2005). Given that RP patients enjoy excellent long-
term cure rates, quality of life issues stemming from RP have
become an important consideration. Neurovascular bundle
damage during RP has been associated with reduced post-RP
erectile function (EF) and a resultant decreased quality of life in
patients (Nelson et al., 2007).
Men who have undergone non-nerve sparing (NNS) RP are
believed to have an extremely low chance of erectile function
investigated EFR in patients receiving unilateral and bilateral
nerve resection (UNR and BNR respectively) in a meaningful
manner. For those studies that do, there is huge variation in
reported rates of EFR, ranging from 13–56% for UNR patients
and 0–17% in BNR RP patients (Dubbelman et al., 2006).
Such broad ranges are of little use when seeking to properly
counsel patients regarding their prospects for EFR following
surgery. In addition, the variation in the reported numbers
stem from multiple factors, ranging from differences in each
study’s patient demographics, data acquisition methods,
duration of post-operative follow up, differences in patient
baseline EF and even the definition of what actually
constitutes ED and EFR (Mulhall, 2009; Moskovic et al.,
2011).

© 2014 American Society of Andrology and European Academy of Andrology Andrology, 2014, 2, 951–954 951
R. Krishnan et al.
Another important yet often overlooked factor in predicting
EFR is accounting for the degree of nerve injury during RP. Stud-
ies have typically assessed cavernous nerve damage using an
‘all-or-nothing’ or ‘absolute’ approach, grouping nerve damage
into one of three outcomes: bilateral, unilateral or NNS surgery
(Quinlan et al., 1991; Marien et al., 2009; Moskovic et al., 2011).
This particular grading scheme for nerve injury has received crit-
icism in recent years for its inability to accurately describe the
degree of neurovascular damage and thus yielding imprecise
and varying EFR rates in studies (Burnett et al., 2007; Marien
et al., 2009; Tal et al., 2009; Moskovic et al., 2011). As EFR can be
significantly affected by the degree of nerve damage, it therefore
follows that assessing nerve damage using a binary ‘all-or-noth-
ing’ scheme ignores nuances crucial to patient EF outcomes
(Levinson et al., 2008; Rabbani et al., 2000).
To our knowledge, no study to date has looked at characteriz-
ing long-term EFR rates in NNS RP patients using a nerve-spar-
ing grading scheme along with a validated EF assessment
methodology. Our goal therefore was to define the rate of long-
term EFR and the associated predictive factors in patients under-
going unilateral and bilateral nerve resection RP.
MATERIALS AND METHODS
Patient population
We reviewed prospectively collected data on patients receiving
either laparoscopic or open RP at a tertiary referral cancer cen-
tre. Patients who received radiation or androgen deprivation
therapy at any point prior to or during the study were excluded
from analysis. The study was approved by the Institutional
Review Board and all subjects provided prior informed consent.
Demographic variables and the number of vascular risk factors
(VRF) present for each RP patient were assessed prior to surgery.
VRFs evaluated for this study were hypertension, diabetes mell-
itus, hypercholesterolemia, coronary artery disease and cigarette
smoking.
Erectile function outcomes measure
An EF scale was used to assess patient EF. EF scoring was
determined through physician-patient interview conducted by
the treating urological surgeon during an office visit as part of
the pre-operative visit and during all post-operative visits there-
after. In addition, patient demographic and clinical data were
collected by research coordinators via direct patient contact as
such factors have established associations with the level of PCa
aggressiveness and overall health affecting EF.
Erectile function was assessed prior to RP and again between
24 and 30 months post-op (24 months EF). Baseline EF was
graded on a validated 5-point patient-reported scale: 1 = fully
rigid, always capable of penetration; 2 = full, diminished erec-
tion, mostly capable of penetration, 3 = partial erection, occa-
sionally satisfactory for intercourse, 4 = tumescence,
unsatisfactory for of intercourse, and 5 = no tumescence. EFR in
all cases was strictly defined as an EF grade of 1 or 2 without the
use of a PDE5i or intracavernosal injections.
Nerve resection grading
To classify the extent of nerve resection in RP patients, we uti-
lized a 4-point nerve sparing score (NSS) where: 1 = fully pre-
served nerve, 2 = partially preserved, 3 = minimally preserved,
952 Andrology, 2014, 2, 951–954
ANDROLOGY
and 4 = resected nerve. Each nerve was assigned an NSS intra-
operatively by the surgeon. For this analysis, bilateral nerve spar-
ing surgery (BNS) was defined as a score of 1 or 2 for both
nerves. Unilateral nerve resection (UNR) was defined as a score
of 1 or 2 unilaterally and a score of 3 or 4 for the contralateral
nerve, and bilateral nerve resection (BNR) was defined as a 3 or 4
for both nerves.
Statistical analysis
Descriptive statistics were used to report patient demographic
variables and percent of patients attaining EFR. Multivariable
analysis was performed using logistic regression to identify fac-
tors predictive of EFR in RP patients. For each of the nerve spar-
ing sub-groups, chi-squared analysis was used to test
significance of categorical variables and Fisher’s exact test was
used when frequency in a cell fell below five. ANOVA was used to
compare mean differences between nerve sparing-sub groups.
All significance testing used a p < 0.05 to define significance.
RESULTS
Patient population
A total of 966 patients were selected for analysis. RP proce-
dures had been performed by 8 surgeons. In the total patient
sample group, the majority of patients, 76% (735 patients)
received BNS RP; 14% of patients received UNR (139 patients)
and approximately 10% (92 patients) received BNR. Patient char-
acteristics are recorded in Table 1.
Fifty-eight percent of the UNR patient group and 67% of the
BNR group were above 60 years of age at time of RP. The num-
ber of VRF present was statistically significant for all subgroups;
however, its clinical significance is negligible, given the age
group and similarity between all subgroups.
EF outcomes
Not surprisingly, BNS patients experienced the greatest rate of
EFR (50%) with pre-RP and post-RP EF scores of 1.5  1.0 and
2.7  1.4 respectively (p < 0.001). In the UNR subgroup, the
mean pre-RP and post-RP EF scores were 1.84  1.3 and
3.3  1.5 respectively with a drop from 78% to 33% of patients
demonstrating EF scores of 1 and 2, 24 months post-op
(p < 0.001). In the BNR group, the average pre-RP and post-RP
EF scores were 2.74  1.5 and 4.2  1.2. Prior to RP, 49% of BNR
patients possessed good EF, a rate which declined to 13% on fol-
low-up 24 months post-RP (Table 2).
EFR declines with age
Univariate analysis revealed increased age to reduce future EFR
prospects in those receiving UNR surgery (RR = 1.72, 95% CI: 1.1–
Table 1 RP patient characteristics based on nerve resection status
Variable BNS UNR BNR p
(n = 735) (n = 139) (n = 92)
Mean age (years) 59  7 60  7 63  7 p < 0.001
Baseline EF (mean) 1.5  1.0 1.8  1.3 2.7  1.5 p < 0.001
Mean no. VRFa 1.2  1.0 1.3  1.2 1.5  1.1 p = 0.01
RP, radical prostatectomy; BNS, bilateral nerve sparing surgery; UNR, unilateral
nerve resection; BNR, bilateral nerve resection; EF, erectile function. aVascular risk
factors: hypertension, hypercholesterolemia, diabetes, coronary artery disease,
cigarette smoking.
© 2014 American Society of Andrology and European Academy of Andrology
ERECTILE FUNCTION RECOVERY IN RP PATIENTS ANDROLOGY
Table 2 Erectile function (24 months) and rate of erectile function recovery recover EF is not well characterized in the literature. There is
(EFR) for RP patients based on nerve resection status high variation seen in reported rates owing to factors such as dif-
Variables BNS UNR BNR p ferences in study populations, data acquisition methods, length
of time until post-operative EF evaluation, a binary ‘all-or-noth-
24 months EF (mean) 2.7  1.4 3.3  1.5 4.2  1.2 p < 0.001 ing’ approach to assessing cavernous nerve injury and the very
EFR (%) 50 33 13 p < 0.001
definition of what constitutes EFR (Mulhall, 2009; Moskovic
RP, radical prostatectomy; BNS, bilateral nerve sparing surgery; UNR, unilateral et al., 2011).
nerve resection; BNR, bilateral nerve resection. Problems with EF have been established as a significant con-
tributing factor to sexual bother and depression in men, years
2.8; p = 0.03). In the UNR subgroup, 43% of patients under after RP (Nelson et al., 2010). Even men who are capable of
60 years experienced EFR 24 months post-op compared with tumescence following RP lose confidence in their sexual perfor-
25% for patients over 60 years. BNR patients exhibited a similar mance ability following frequent inability to achieve and main-
trend of decreased EFR with increased patient age (RR = 3.43, tain erections rigid enough for penetration (Alkhateeb &
95% CI: 1.09–10.52; p = 0.02). Twenty four percent of BNR Lawrentschuk, 2011). Furthermore, Nelson et al. demonstrated
patients under 60 years of age attained EFR 24 months post-op that regardless of age or level of sexual desire at the time of sur-
compared with just 7% of BNR patients above 60 years (Table 3). gery, men did not exhibit significant improvement psychologi-
cally to the loss of EF up to 2 years following RP.
Baseline EF as a predictor of EFR Our data shows that men undergoing nerve resection during
A patient’s baseline EF prior to RP was found to be predictive RP are able to regain functional erections, as defined by our vali-
of attaining EFR 24 months post-op. We compared patients who dated institutional EF scale (Tal et al., 2012), without the use of
had good baseline EF(EF score ≤2) to patients with poor baseline erectogenic medication. The EFR rate seen in patients with BNR
EF (EF score ≥3). There were significant differences in EFR for was encouraging, albeit much lower than those seen in patients
UNR and BNR patients based on baseline EF. In the UNR patient receiving either UNR or BNS surgery. The overall BNR recovery
subgroup, 40% of individuals with good baseline EF experienced rate in this analysis was 13%, higher than that typically seen in
EFR vs. 7% for UNR patients with a poor baseline EF (p = 0.001). other studies. In a meta-analysis of 14 studies looking at EFR
BNR patients with good baseline EF saw 24% of individuals rates following RP, Dubbelman et al. (2006) reported EF rates
achieve EFR after 24 months. None of the 47 BNR patients with ranging from 0 to 17% following NNS surgery. However, the
poor baseline EF experienced EFR after 24 months (p < 0.001) studies analysed did not use validated questionnaires for data
(Table 4). collection or suffered from many of the limitations mentioned
previously. Within the BNR cohort in our analysis, increased
Multivariable analysis recovery rate prospects were strongly associated with younger
In UNR patients, a baseline EF ≤2 was found to be the only sig- patient age (24% EFR for patients <60 years vs. 7% for patients
nificant predictor of future EFR (OR = 8.23; 95% CI = 1.84– ≥60 years). The prospects for EFR were also dramatically
26.78). No multivariable analysis was performed for the BNR improved in patients with excellent pre-RP EF (27% EFR for
subgroup as all patients who recovered EF had pre-RP EF ≤2. baseline EF ≤ 2). In sharp contrast, none of the BNR patients
who underwent RP with a poor baseline EF (EF ≥ 3) were able to
DISCUSSION attain EFR 24 months post-op.
Quality of life-related complications continue to persist for These results are significant because they show that men
post-RP patients, especially those having had deliberate nerve undergoing deliberate nerve resection during RP still have a low
resection. The ability of patients who receive NNS surgery to but significant chance of achieving EFR. Generally, BNR patients
are not considered candidates for penile rehabilitation. The close
Table 3 Erectile function recovery (EFR) rates in UNR and BNR patients association of EFR in younger BNR patients with already excel-
based on age lent baseline EF underscores the importance of evaluating a
Nerve resection status Age EFR rate (%) RR 95% CI p
patient’s EF and age prior to deliberate nerve resection.
The EFR results seen for UNR patients (33% EFR overall) were
UNR <60 (n = 76) 43 1.72 1.1–2.8 0.03 on the lower end of the range seen in other clinical studies. In a
≥60 (n = 63) 25
meta-analysis by Tal et al. looking at 22 recent clinical studies of
BNR <60 (n = 58) 24 3.43 1.1–10.5 0.02
≥60 (n = 34) 7 EFR rates post-operatively, the average overall EFR rate in
patients after a period of 18 months was found to be at 60%,
UNR, unilateral nerve resection; BNR, bilateral nerve resection.
appreciably higher than the rates seen in this study. In the same
analysis, younger patients (<60 years) had a higher EFR rate of
Table 4 Erectile function recovery (EFR) rates in UNR and BNR patients
77% compared with older patients (≥60 years) at 61% EFR. The
based on baseline EF
reason for a difference in stated recovery rates is two-fold. Many
Nerve resection status Baseline EFR RR 95% CI p studies looking at EFR rates include patients using erectogenic
EF rate (%) therapies, making it difficult to ascertain the extent of EF without
UNR ≤2 (n = 109) 40 5.71 1.6–23.1 p = 0.001 such interventions. Furthermore, Tal et al. highlighted that 13/
≥3 (n = 30) 7 22 recent publications analysed studied subjects who used some
BNR ≤2 (n = 45) 27 NA NA NA form of erectogenic therapy. None clearly delineated the extent
≥3 (n = 47) 0
of erectogenic therapy use or the impact of such intervention on
UNR, unilateral nerve resection; BNR, bilateral nerve resection. the study’s respective findings.

© 2014 American Society of Andrology and European Academy of Andrology Andrology, 2014, 2, 951–954 953
R. Krishnan et al.
Our data showed that the extent of EFR experienced after RP
was highly dependent on baseline EF prior to surgery. EFR pros-
pects were most favourable in those with excellent baseline EF
(≤2) prior to surgery. For those men receiving UNR, 40% of men
with excellent baseline EF (grade ≤2) compared with just 7% with-
out excellent EF (grade ≥3). Multivariable analysis revealed that
in UNR patients, baseline EF was a significant predictor of EFR at
24 months. No multivariable analysis was performed for the BNR
cohort as all men who recovered EFR had a baseline EF ≤ 2.
This analysis has a number of strengths. The population size
of 966 is larger than the typical EFR study where the mean study
sample size is 226.5  384 (Tal et al., 2009). The study also fol-
lows patients over a longer period of time, 24–30 months follow-
ing surgery, a time-point that is recognized as a reasonable point
at which to assess long-term EFR.
Thirdly, the definition of EFR is more aligned with what
patients would typically consider to be functional erections.
Many studies have utilized a broader, less rigorous definition of
EFR (Mulhall, 2009; Tal et al., 2009). Such studies considered
erection frequencies of ‘sometimes’ or ‘occasionally’ as suffi-
cient for satisfying a favourable erection outcome. Our clinical
experience and numerous studies have shown that patients typi-
cally consider recovery to mean a return to their EF status pre-
RP (Schroeck et al., 2008; Mulhall et al., 2010; Alkhateeb & Law-
rentschuk, 2011). Thus, a looser definition of EFR can convey
improper expectations to patients of their long-term EFR pros-
pects. Aligning the definition of EFR and its proper conveyance
to the patient is therefore crucial to managing expectations. This
was the primary reason that our analysis defined EFR as a return
to excellent EF, that is, a full erection that is always or almost
always capable of erection (EF grade of 1–2).
Finally, patients were evaluated on a graded scale of nerve
injury, allowing for increased nuance in understanding a
patient’s chance at achieving EFR (Moskovic et al., 2011). This
nerve scoring scale has previously been published and validated
at our institution. Furthermore, we utilized an EFR scale devel-
oped at our institution and not one of the more frequently used
scoring questionnaires (International Index of Erectile Function,
IIEF) as the study commenced prior to the routine use of the
IIEF. However, we recently demonstrated that the 5-point scale
used in this analysis correlates closely with the EF domain score
of the IIEF and indeed correlates nicely with the different levels
of EF: grade 1, 2 = good EF, 3 = mild ED, 4 = moderate ED and
5 = severe ED (Tal et al., 2009).
The study is not without some limitations. We do not have
excellent serial follow-up on most patients with some being seen
at baseline and only late after RP, thus we cannot comment on
the chronology of recovery.
CONCLUSION
No studies to date have reliably studied long-term EFR rates in
a large population of NNS patients using stringent criteria for
EFR while considering the extent of cavernous nerve damage.
Our analysis showed that men undergoing NNS RP still have a
significant chance of long-term EFR without the use of medica-
tion. No patients, however, with poor baseline EF undergoing
BNR RP achieved EFR. Thus, physicians should measure base-
line EF in addition to considering age and the degree of nerve
resection when advising patients about expectations for success-
ful EF following surgery.
954 Andrology, 2014, 2, 951–954
ANDROLOGY
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