1. Introduction
During the COVID-19 pandemic, overall screening, diagnostics, and treatment have faced a downtrend, especially during the first wave and lockdown, with the statistics slowly improving by the late era of the pandemic or by the end of 2020. To improvise, the risk of delayed curative treatment was measured and treatment plans were amended to lower hospital visits while the results are still contradictory. In this review, we comprehensively reviewed additional burdens to patients with prostate cancer and different aspects of the quality of life that the COVID-19 pandemic brought.
2. The effect of delayed treatment
Compared to the 2019, there was an average 23% reduction in surgical volume between March and December 2020 in 8 European tertiary referral centers.[1] No association was observed between surgical delay and oncologic outcomes for a large European cohort of 926 men with a median 3 months delay.[2] According to a National Cancer Database study of 128,062 men with intermediate and high-risk prostate cancer, there was no significant difference in the pathology, node-positive disease, or post-radical prostatectomy secondary treatments between those who received immediate radical prostatectomy and those who experienced any level of delay up to 12 months.[3] There was no significant association between the length of time to radical prostatectomy and risk of developing metastases.[3] However, Zattoni et al, 2021 suggested that patients who were treated during the pandemic had a higher risk of extra-prostatic disease and lymph node invasion due to a delay in the administration of curative-intent therapies in patients with localized prostate cancer.[1]
A meta-analysis of four randomized controlled trials found that overall survival and cancer-specific survival significantly worsened among intermediate-risk patients but not in the case of low- and high-risk patients whose treatment was delayed. It was suggested that a 3-month course of neoadjuvant hormone therapy could improve pathological outcomes but not oncological outcomes.[4]
Other than radical prostatectomy, to reduce the frequency of hospital visits, switching from gonadotropin-releasing hormone antagonists to luteinizing hormone-releasing hormone agonists was also a comparable option that does not diminish efficacy or worsen adverse events.[5]
| Author, year | Baseline | Result | Measure | Period of interest (1) | Result | Period of interest (2) | Result |
|---|---|---|---|---|---|---|---|
| Ip, 2021[17] | 2018 to 2019 | 121,096,335 | Physician attendances (including telehealth) | 2019-2020 | 114,089,347 (6% reduction) | 2020-2021 | 99,330,510 (18% reduction) |
| 692,021 | PSA tests | 657,468 | 2020-2021 | 706,088 | |||
| 135,775 | Free-to-total PSA tests | 140,024 | 156,321 | ||||
| 31,750 | Multi-parametric MRI | 35,672 | 35,942 | ||||
| 19,923 | Prostate biopsy | 21,453 | 21,574 | ||||
| Ferrari, 2021[18], median (IQR) | 2016 to 2019 | 283 (271 to 288) | Vit D | Lockdown (Mar to May, 2020) | 66 (48 to 126) | ||
| 146 (129 to 147) | Total PSA | 62% (median decrease) | |||||
| 2016 to 2019 | 256 (228 to 280) | Vit D | Post-lockdown | 295 (267 to 322) | |||
| 135 (116 to 151) | Total PSA | 181 (165 to 201) | |||||
| Fallara, 2021[19] | 2017 to 2019 | 2,285 | Total cases | 2020 | 1,458 (36% fewer) | ||
| Stroman 2021[20], number of centers | Prostate MRI | During the pandemic | 14 (13%) centers stopped 39 (37%) centers offered with same indications 48 (46%) centers offered to selected high-risk patient group only | ||||
| Before the pandemic | 68 | LATP | During the pandemic | 56 | |||
| 85 | GATP | 32 | |||||
| 83 | LATRUS | 34 | |||||
| Surasi 2021[21], mean (SD) per week | Before the pandemic | 26.0 (26.0) | Prostate MRI | Lockdown period | 11.6 (8.2) | After lockdown | 21.3 (25.3) |
| 7.9 (11.7) | Prostate biopsy | 2.3 (3.3) | 9.6 (8.0) | ||||
| Pepe 2021[22] | 2019 to 2020 | 2,000 | Clinical office evaluation | 2020 to 2021 | 1,015 | ||
| 351 | Multi-parametric MRI | 85 | |||||
| 485 | Prostate biopsy | 201 | |||||
| 187 (38.5%) | Cancer diagnosis from biopsy | 96 (47.7%) | |||||
| Kaufman 2021[23], average monthly number | Prepandemic | 465,187 | PSA tests | Early Pandemic | 295,786 (36.4% decrease) | Late Pandemic | 483,374 (3.9% increase) |
| 659 | PSA results ≥ 50 ng/mL | 506 (23.2% decrease) | 674 (2.3% increase) | ||||
| 1,453 | Prostate biopsy results | 903 (37.9% decrease) | 1,190 (18.1% decrease) | ||||
| 182 | Gleason score ≥ 8 | 130 (28.6% decrease) | 161 (11.5% decrease) | ||||
| Nossiter 2022[24] | 2019 | 9,918/25,936 (38.2%) | Transperineal/prostate biopsy | 2020 | 10,592/16,551 (64.0%) | ||
| 2019 | 32,409 | Diagnoses | 2020 | 22,419 (30.8% reduction) | |||
| Deukeren 2022[25] | 2019 | 21,542 | Diagnoses | 2020 | 18,444 | End of 2020 | Restored to approximately 95% of expectation |
| 13,621 (63.2%) | N (%) of malignant pathology | 12,756 (69.2%) |
3. Quality of life of patients with prostate cancer
COVID-19 did not add or induce significant anxiety in men being treated for prostate cancer,[6] but those whose operations were postponed had higher state anxiety levels than trait anxiety levels, with the younger population having been more affected by the pandemic.[7] The mean Beck Depression Inventory score was 4.3 (range, 0 to 13), signifying mild depression. This is comparable to a pre-pandemic study that identified that PSA level, patient age, and a number of comorbidities are not related to anxiety and depression in patients with prostate cancer.[8]
Additional challenges existed with patients with prostate cancer receiving ADT during the pandemic. A Portuguese prostate cancer study evaluating the Montreal Cognitive Assessment demonstrated that cognitive decline was more frequent in the ADT group, and declined even more after the onset of the COVID-19 pandemic.[9] According to a meta-analysis of three RCTs in male patients with prostate cancer on or previously treated with androgen suppression therapy, body fat is likely to be increased during COVID-19 restriction, possibly affecting metabolic health.[10]
| Author, year | Baseline | Result | Measure | Period of interest (1) | Result | Period of interest (2) | Result |
|---|---|---|---|---|---|---|---|
| Sciarra 2020[26] | 2019 | Radical prostatectomy | 2020 | 63.6% reduction | |||
| Radiotherapy | 84.6% reduction | ||||||
| Fallara 2021[19] | 2017 to 2019 | 1,622 | Radical prostatectomy | 2020 | 1,574 (3% reduction) | ||
| 1,176 | Radical radiotherapy | 1,547 (32% increase) | |||||
| 946 | ADT | 709 (25% reduction) | |||||
| Ip 2021[17] | 2018 to 2019 | 6,259 | Radical prostatectomy | 2019 to 2020 | 7,107 | 2020 to 2021 | 6,477 |
| 2,419 | Prostate fiducial markers | 2,807 | 2,962 | ||||
| Pepe 2021[22] | 2019 to 2020 | 54 | Radical prostatectomy | 2020 to 2021 | 39 | ||
| 47 | External radiotherapy | 52 | |||||
| pT3b: 11.2% nodal (+): 14.8 % metastatic: 5.9% | % of advanced, metastatic prostate cancer after prostatectomy | pT3b: 25.6% nodal (+): 46.1% metastatic: 9.3% | |||||
| Nossiter 2022[24] | 2019 | 5,331 | Radical prostatectomy | 2020 | 3,896 (26.9% reduction) | ||
| 11,309 | Radical radiotherapy | 9,719 (14.1% reduction) | |||||
| 785 | Brachytherapy | 470 (40.1% reduction) | |||||
| Deukeren 2022[25], odds ratio (95% CI) | Low-risk localized. intermediate-risk, localized, high-risk, or localized/locally advanced | Radical prostatectomy | 2020 versus 2018 to 2019 |
1.32 (1.01 to 1.72) 1.25 (1.07 to 1.47) 1.16 (1.02 to 1.31) |
|||
| Deukeren 2022[25], odds ratio (95% CI) | Low-risk localized. intermediate-risk, localized, high-risk, or localized/locally advanced | External beam radiotherapy and brachytherapy | 2020 versus 2018 to 2019 |
1.09 (0.71 to 1.67) 1.26 (1.05 to 1.51) 0.99 (0.83 to 1.17) |
|||
| Brachytherapy |
1.17 (0.80 to 1.72) 0.63 (0.49 to 0.82) 0.99 (0.83 to 1.17) |
||||||
| Metastatic | ADT & radiotherapy | 2.27 (1.77 to 2.91) | |||||
Through a computational linguistic ethnography analysis of posts online, a more collective tone (we, affiliation, friends) was present, with increased concern about health and death in 2020.[11] Significant concerns on the impact of COVID-19 on delayed the care or the effect of prostate cancer on COVID-19, and the risks of COVID-19 itself were discussed.[11]
4. Vaccination and prostate cancer
Vaccination against COVID-19 also poses many new challenges, one of them being the presence of vaccination-associated lymphadenopathy. A non-specific increase in ipsilateral axillary lymph nodes after vaccination was commonly reported through PET/CT scans.[12] Notohamiprodjo et al., 2022 observed vaccination-associated lymphadenopathy on 18F-rhPSMA-7.3 PET with a prevalence of 45% in patients with prostate cancer, with the standardized uptake value ratio dropping significantly after 8 weeks.[13]
There were concerns about the impaired immune response to vaccination in prostate cancer: in a study of patients with hormone-refractory metastatic prostate cancer, the CD4+ T cells of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of unexposed patients had decreased CD4+ T cell immune responses to antigens from SARS-CoV-2 spike glycoprotein but not from the spiked glycoprotein of the ‘common cold’-associated human coronavirus 229E (HCoV-229E) as compared with healthy controls who responded comparably to both antigens.[14] However, a study analyzing the median titers of neutralizing antibodies against SARS-CoV-2 of twenty-five patients with prostate cancer under treatment with androgen receptor-targeted agents such as abiraterone or enzalutamide, found it to be similar to healthy volunteers.[15]
A different study suggested that a beneficial impact of COVID-19 vaccination on patients with prostate cancer as the SARS-CoV-2 spike protein reduced the survival of prostate cancer cells through inhibition of proliferation and promotion of apoptosis; downregulation of pro-proliferative molecule CDK4 and upregulation of pro-apoptotic molecule Fas ligand.[16]
5. Conclusions
During the COVID-19 pandemic, overall screening, diagnostics, and treatment have faced a downtrend, especially during the first wave and lockdown, with the statistics showing slow improving during the late era of the pandemic or by the end of 2020. To improvise, the risk of delayed curative treatment was measured, and treatment plans were amended accordingly in order to lessen hospital visits while the results are still contradictory. The protective role of androgen deprivation therapy on COVID-19 triggered many debate while the majority of clinical studies found no significant association. Concerns about a reduced immune response to vaccination in patients with prostate cancer occurred, but additional research in the future essential. The pandemic added additional burdens to patients with prostate cancer and different aspects of the quality of life of patients were assessed. While we anticipate that the end of the pandemic this coming, it is essential to re-examine how the pandemic has changed the overall care of patients with prostate cancer and how to proceed further in the future.
