DISCUSSION
In patients with localized PCa, our results showed that surgical margin
status, LN positivity and the presence of ECE were similar irrespective
of waiting period between the diagnosis and RP, however there was a
slightly more SV invasion rate in final RP pathology of patients with a
“diagnosis to surgery time” less than or equal to 90 days. Similarly
in low-risk subgroup, Gleason Grade group upgrading in RP was found to
be significantly higher in group 1 compared to group 2. However, 5-year
biochemical recurrence free survival rates were similar in all three
risk categories between the two study groups. In high-risk patients, the
need for adjuvant treatment was higher in group 1 and the regression
analysis demonstrated that the only factor affecting time to PSA
progression in high-risk patient population was SV invasion at the RP
pathology.
In the present study, median time elapsed until treatment was 119
(104-141) days in group 2 and biochemical recurrence rate in high risk
patient category at this cut-off point (22.6%) was not statistically
significant. (p=0.605, Data not shown) Since the number of patients with
a delay time of more than 4 months were limited in our study, it was not
possible to determine a safe cut-off time. On the other hand, our
results clearly indicated a safe waiting period up to 4 months. In order
to comment on longer delay times studies including more patients with
longer wait times are needed.
This is one of the studies with the largest number of patients on this
subject. Since our data source is a nationwide database with patient
information from reference centers all around the country, results could
be generalized to general population in Turkey. Most of the published
data on surgical delay times are derived from AS studies and conducted
in low/intermediate risk groups.8, 9 There are few
studies which include high-risk PCa patients but there is no uniformity
in these studies with respect to risk classification criteria or time
cut-off levels for surgical delay.10, 11 Our study is
also one of the few studies that included all of the risk groups.
Patients who first enrolled in AS are excluded from our study which
enabled us to asses time delay more objectively, especially in low-risk
patients.
Decision making about a treatment modality from the available options
could be challenging for PCa patients, especially in localized disease.
Also, as the Covid-19 pandemic demonstrated, in some situations public
health regulations and status of health care systems could necessitate a
delay in the treatment of patients. In most cases guidelines specifies
the treatment options but has no comment on the timing of the treatment.
For most of the cancer types there are debates on the time intervals and
their effect on the oncological outcomes.12
Urological cancers are no exception on these debates and there are some
studies investigating the effect of treatment delay in all urological
cancers. Urothelial cancer which is a typical example, has proven to be
adversely effected by the delay in treatment. Hollenback et.al. showed
that more than 25% of patients had delays of more than 3 months from
the first occurrence of hematuria to definitive diagnosis. They also
demonstrated that patients with a longer delay needed more radical
interventions including cystectomy and the mortality rate was higher in
this group.13 On the other hand Wallace et.al. showed
that, although a shorter delay in the hospital did not have a profound
impact, longer delays in treatment due to factors associated with
referral patterns cause worse outcomes. 14
Testicular cancer was traditionally regarded as a urological emergency.
Although there are some reports demonstrating the adverse effect of
treatment and diagnosis delay in testicular cancer15,
16, there are also studies that do not show any benefit of early
surgery in seminomatous tumors.17, 18 Since timing of
surgery is still controversial, there are no recommendations regarding
the time of orchiectomy in the guidelines of EAU. Physicians also
encouraged to offer sperm cryopreservation to the patients before
orchiectomy in EAU guidelines, which could result in short delays in
surgery. 19
The data on treatment delays in renal cell carcinoma is even more
limited. There are reports indicating that the delays in surgery has no
impact on disease specific survival for small (<4 cm) renal
masses.20, 21 On the other hand, for renal masses more
than 4cm diameter surgery is recommended before one month in a recent
review, although there is no objective evidence demonstrating the
adverse effect of late surgery. 22
Studies on the effect of surgical delay on PCa prognosis are also
conflicting. In 2017 a Canadian study demonstrated that even in patients
with high-risk disease, surgical wait time does not affect pathological
outcome after robot assisted RP (RARP).23 Furthermore,
a recent study conducted on 2303 men demonstrated that in unfavorable
prognosis group a waiting period up to 6 months does not have any
adverse effect on disease outcomes.11 Similarly,
Morini et. al. showed that even in patients who had waiting period of
more than 6 months before treatment, oncological results were not
adversely effected.24 There are other studies which
reported similar results and could not find association between surgical
delay time and disease progression.25-27
Despite the results of some studies showing no effect of surgical delay
times in PCa patients, there are also contrasting reports which
demonstrate delay in time to treatment as an unfavorable prognostic
factor. In a series of 1111 low-risk PCa patients O’Brien et. al.
reported worse oncological outcomes for patients who waited more than 6
months for the surgery. 28 A more recent study
performed on RARP patients showed that increased duration from biopsy to
surgery may lead to more biochemical recurrence in high-risk
group.10
Our study in concordance with the previous studies, showed no
correlation between the surgical delay and biochemical recurrence free
survival in overall patient cohort and after risk group stratification.
Although some studies demonstrated a worse outcome with prolonged
surgical delay time in high risk patients, those reports were limited in
patient numbers and had different time cut-offs. Absence of a
standardized definition on duration of cut-off in studies may be the
underlying reason for contrasting results in different studies.