# The Rebound Effect of the COVID-19 Pandemic on Clinically Significant Prostate Cancer Diagnosis
## 4 Discussion  
While it is well established that the COVID-19 pandemic led to delays in screening and treatment for various malignancies, including major urological cancers, our study aimed to precisely quantify the impact of delayed prostate biopsy on prostate cancer diagnosis. As expected, the COVID period was associated with a significant decrease in the number of biopsies performed when compared with the pre-COVID and post-COVID period. This reduction was particularly evident between March and May 2020, when the pandemic reached its peak in Italy. Interestingly, the decrease in the number of biopsies performed resulted in a decrease in the detection rate of csPCa but not in the detection rate of non-cs PCa, which remained stable across the three periods. This is of particular clinical relevance, as the delay in diagnosing csPCa may lead to disease progression, potentially affecting treatment outcomes and patient prognosis. By providing a more precise quantification of this impact, our study contributes valuable data to the ongoing discourse on how healthcare disruptions during the pandemic influenced prostate cancer detection. A systematic review assessing the impact of COVID-19 on the screening and diagnosis of PCa [19] analyzed 40 studies and found that the majority of them reported a significant decrease in prostate-specific antigen (PSA) tests during the COVID-19 pandemic, when compared with the pre-pandemic period. This decline in screening led to a delay in cancer diagnosis. The decrease in PCa screening and diagnosis indeed varied widely across examined studies, ranging from nearly 0% to 78% for screening and from 4.1% to 71.7% for diagnosis. Similarly, a Dutch report [20] showed a significant decrease in PCa diagnosis during the first wave of the COVID-19 pandemic, with a subsequent recovery by the end  
Figure 2: Histogram comparing the number of diagnoses of csPCa and ncsPCa. csPCa: clinically significant prostate cancer; ncsPCa: non clinically significant prostate cancer. of 2020, although there was still a shortfall of at least 5% in the expected diagnosis rate. Our study pointed out that the reduction in PCa diagnosis occurred for csPCa only, while the detection rate of non-csPCa surprisingly remained stable throughout all tested periods. Differently from the Dutch study, there was a rebound effect in the detection rate of csPCa in the post-COVID period; this finding was somehow expected as the consequence of the reduced number of prostate biopsies and csPCa diagnosis over the COVID period, suggesting a possible stage migration due to delayed diagnosis. However, questions remain whether such findings have an impact on oncological outcomes [21]. While it is logical that delaying diagnosis and treatment may hamper the oncological outcome, a recent study [22] showed that the increased surgical wait time due to the COVID pandemic did not increase the risk of node-positive prostate cancer. It is, however, worth mentioning that this may be true for low-intermediate-risk PCa but may not apply to high-risk PCa. In the above-mentioned systematic review [19], the reduction in the cancer detection rate of low/intermediate-stage cancers during the COVID period was somewhat greater than that observed for cancers of advanced stages. We acknowledge that the lack of long-term oncological outcomes is a notable limitation of our study. However, we believe that a minimum follow-up of ten years is required to accurately evaluate even intermediate endpoints such as biochemical recurrence and metastasis. Given the relatively short timeframe of our study, drawing meaningful conclusions on oncological outcomes remains challenging, even if the follow-up was extended to the present. Another relevant issue is the time between medical consultation and surgery for PCa.