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.