A low prostate specific antigen predicts a worse outcome in high but not in low/intermediate-grade prostate cancer

Fankhauser, Christian Daniel; Parry, Matthew G.; Ali, Adnan; Cowling, Thomas E; Nossiter, Julie; Sujenthiran, Arun; Berry, Brendan; Morris, Melvin L.; Aggarwal, Ajay; Payne, Heather; Meulen, Jan van der; Clarke, Noel W.

doi:10.1016/j.ejca.2022.12.017

Cited by 4 publications

(6 citation statements)

References 25 publications

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“…1 It is also unclear how well PSA levels predict outcomes for low and intermediate-risk cancers. 2 Importantly, men who progress through the diagnostic pathway may suffer from physical and psychological issues such as anxiety.…”

Section: Introductionmentioning

confidence: 99%

“…However, the use of PSA to determine diagnostic pathway progression has been linked to overdiagnosis, with one study reporting that 70%–80% of patients with PSA levels >4 ng/mL did not in fact have cancer 1 . It is also unclear how well PSA levels predict outcomes for low and intermediate‐risk cancers 2 . Importantly, men who progress through the diagnostic pathway may suffer from physical and psychological issues such as anxiety.…”

Section: Introductionmentioning

confidence: 99%

“… 1 It is also unclear how well PSA levels predict outcomes for low and intermediate‐risk cancers. 2 Importantly, men who progress through the diagnostic pathway may suffer from physical and psychological issues such as anxiety. More specifically, prostate biopsies have been associated with bleeding, urinary retention issues as well as infectious complications (0.1%–7%) and sepsis (0.3%–3.1%), which can vary depending on the antibiotic prophylaxis regimens implemented.…”

Section: Introductionmentioning

confidence: 99%

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The impact of pre‐biopsy MRI and additional testing on prostate cancer screening outcomes: A rapid review

Tesfai,

Norori,

Harding

et al. 2024

BJUI Compass

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ObjectiveThis work aims to examine the latest evidence on the impact of pre‐biopsy MRI, in addition to prostate‐specific antigen (PSA) testing, on health outcomes and quality of life.MethodsWe conducted a literature search including PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases, with a limited scan of (i) guidelines and (ii) references from trial reports, from January 2005 to 25th January 2023. Two independent reviewers selected randomised controlled trials (RCT) and cohort studies which met our inclusion criteria.ResultsOne hundred thirty‐seven articles were identified, and seven trial articles were selected. Trial interventions were as follows: (i) PSA blood test, (ii) additional tests such as pre‐biopsy multiparametric magnetic resonance imaging (mpMRI) and Biparametric MRI (bpMRI), and (iii) MRI targeted biopsy and standard biopsy. Compared with standard biopsy, MRI‐based interventions led to increased detection of clinically significant cancers in three studies and decreased detection of clinically insignificant cancer (Gleason grade 3 + 3) in four studies. However, PROstate Magnetic resonance Imaging Study (PROMIS) and Stockholm3 with MRI (STHLM3‐MRI) studies reported different trends depending on the scenario studied in PROMIS (MRI triage and MRI directed biopsy vs. MRI triage and standard biopsy) and thresholds used in STHLM3‐MRI (≥0·11 and ≥0·15). MRI also helped 8%–49% of men avoid biopsy, in six out of seven studies, but not in STHLM3‐MRI at ≥0.11. Interestingly, the proportion of men who experienced sepsis and UTI was low across studies.ConclusionThis review found that a combination of approaches, centred on the use of pre‐biopsy MRI, may improve the detection of clinically significant cancers and reduce (i) the diagnosis of clinically insignificant cancers and (ii) unnecessary biopsies, compared with PSA testing and standard biopsy alone. However, the impact of such interventions on longer term outcomes such as prostate cancer‐specific mortality has not yet been assessed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The impact of pre‐biopsy MRI and additional testing on prostate cancer screening outcomes: A rapid review

Tesfai,

Norori,

Harding

et al. 2024

BJUI Compass

View full text Add to dashboard Cite

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“…In general, achieving a low or undetectable PSA level has been associated with favourable long-term outcomes after proctectomy, radiation therapy and systemic therapy. [3][4][5][6][7][8][9] Conversely, some tumours evolve to low PSA secretion and demonstrate a very aggressive biology. 10,11 Thus, a mixture of favourable and poor prognoses exists among patients with low PSA.…”

Section: Introductionmentioning

confidence: 99%

“…It remains an open question as to how the absolute value of PSA should influence imaging practices, particularly among patients who achieve very low PSA levels with treatment. In general, achieving a low or undetectable PSA level has been associated with favourable long‐term outcomes after proctectomy, radiation therapy and systemic therapy 3–9 . Conversely, some tumours evolve to low PSA secretion and demonstrate a very aggressive biology 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Low PSA radiographic disease progression on C11‐choline PET

Mahmoud,

Ahmed,

Kendi

et al. 2023

BJUI Compass

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BackgroundFor men with prostate cancer, radiographic progression may occur without a concordant rise in prostate‐specific antigen (PSA). Our study aimed to assess the prevalence of radiographic progression using C‐11 choline positron emission tomography (PET) imaging in patients achieving ultra‐low PSA values and to evaluate clinical outcomes in this patient population.MethodsIn a single institution study, we reviewed the prospectively maintained Mayo Clinic C‐11 Choline PET metastatic prostate cancer registry to identify patients experiencing radiographic disease progression (rDP) on C‐11 choline PET scan while the PSA value was less than 0.5 ng/mL. Disease progression was confirmed by tissue biopsy or response to subsequent therapy. Clinicopathologic variables were abstracted by trained research personnel. Overall survival was estimated using the Kaplan–Meier method. Intergroup differences were assessed using the log‐rank test. A univariate and multivariate Cox regression model was performed to investigate variables associated with poor survival after rDP.ResultsA total of 1323 patients within the registry experienced rDP between 2011 and 2021, including 220 (16.6%) men with rDP occurring at low PSA level. A median (interquartile range [IQR]) of 54.7 (19.7–106.9) months elapsed between the time of prostate cancer diagnosis and low PSA rDP, during which 173 patients (78%) developed castration‐resistant prostate cancer (CRPC). Sites of low PSA rDP included local recurrence (n = 17, 8%), lymph node (n = 90, 41%), bone (n = 94, 43%) and visceral metastases (n = 19, 9%). Biopsy at the time of rDP demonstrated small‐cell or neuroendocrine features in 21% of patients with available tissue. Over a median (IQR) follow‐up of 49.4 (21.3–95.1) months from the time of low PSA rDP, 46% (n = 102) of patients died. Factors associated with poorer survival outcomes include advanced age at rDP, CRPC status, bone and visceral metastasis (p value <0.05). Visceral metastases were associated with decreased overall survival (p = 0.009 by log‐rank) as compared with other sites of rDP.ConclusionsMen with prostate cancer commonly experience metastatic progression at very low or even undetectable PSA levels. Periodic imaging, even at low absolute PSA values, may result in more timely identification of disease progression.

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Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels

Mahal,

Kwak,

Xie

et al. 2023

JAMA Netw Open

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ImportancePatients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; &lt;4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm.ObjectiveTo assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer–specific mortality (PCSM) and all-cause mortality (ACM).Data SourcesPubMed search from 2000 to 2022.Study SelectionFive prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel.Data Extraction and SynthesisIndividual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022.Main Outcomes and MeasuresHazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months).ResultsFrom a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]).Conclusions and RelevanceAdding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.

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A low prostate specific antigen predicts a worse outcome in high but not in low/intermediate-grade prostate cancer

Cited by 4 publications

References 25 publications

The impact of pre‐biopsy MRI and additional testing on prostate cancer screening outcomes: A rapid review

The impact of pre‐biopsy MRI and additional testing on prostate cancer screening outcomes: A rapid review

Low PSA radiographic disease progression on C11‐choline PET

Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels

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