Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature.

Smith, David C.; Tucker, John; Trump, Donald L.

doi:10.1200/jco.1992.10.3.499

Cited by 49 publications

(17 citation statements)

References 41 publications

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“…17 Indeed, when reviewed, the rare instances of hypercalcemia in patients with prostate carcinoma have been associated largely with neuroendocrine carcinomas. 18 The high rate (9%) of hypercalcemia in the current study reinforces the differing biologic nature of the PSA-negative tumor despite the absence of neuroendocrine differentiation.…”

Section: Discussionsupporting

confidence: 65%

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL

Birtle

Freeman

Masters

et al. 2003

Cancer

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BACKGROUNDAlthough < 1% of men present with prostate‐specific antigen (PSA)‐negative prostate carcinoma, in that they have serum PSA levels much lower than the tumor burden would suggest, such patients represent a management dilemma. To the authors' knowledge, little information exists in the literature regarding patterns of disease and response to treatment. The authors wished to define the clinical features of this patient group.METHODSThe British Association of Urological Surgeons Cancer Registry 2000 and 2001 data bases were used to identify the clinical features and outcome of 33 men with metastatic prostate carcinoma who presented with serum PSA levels < 10 ng/mL. Clinical notes and histopathology were reviewed for each patient.RESULTSSeventeen patients (51%) presented with urinary symptoms and/or pelvic pain, 6% with cachexia and 21% with bone pain. Characteristic bone metastases were present in 81% of patients, similar to the presentation of men with high serum PSA levels. Hypercalcemia was a feature in 9% of patients. Visceral metastases were present in two patients. The median response duration to first‐line hormone manipulation was 7 months. No responses were seen in 11 of 13 patients who received second‐line hormones or to any third‐line treatment. Three of 5 patients who received chemotherapy responded but developed recurrent disease within 8 weeks of treatment cessation. The median overall survival was 12 months.CONCLUSIONSThe presentation of patients with treatment‐naïve PSA‐negative metastatic prostate carcinoma is similar to that of patients with high serum PSA levels, but their median survival and response duration to first‐line hormone therapy are of much shorter duration. Second‐line hormone therapy is ineffective, but early chemotherapy may be beneficial. Hypercalcemia is a particular feature in this group of patients. Cancer 2003. © 2003 American Cancer Society.

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Section: Discussionsupporting

confidence: 65%

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL

Birtle

Freeman

Masters

et al. 2003

Cancer

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“…Although PTHrP expression in localized prostate cancer is common, hypercalcemia in advanced prostate cancer is rare, accounting for less than 2% of published cases (23). Men with metastatic prostate cancer often develop low normocalcemia or hypocalcemia because blastic metastases in bone (the site of the overwhelming majority of metastases in prostate cancer) trap serum calcium into the bony lesions (24).…”

Section: Discussionmentioning

confidence: 99%

A Prospective Study of Total and Ionized Serum Calcium and Time to Fatal Prostate Cancer

Schwartz

Skinner

2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Higher levels of total and ionized serum calcium have been shown to predict fatal prostate cancer in prospective studies. Because the follow-up time in these studies was relatively short, these associations could reflect the effect of clinically significant but occult prostate tumors on serum calcium levels. If this were true, prostate cancer mortality rates among men with higher levels of serum calcium should be higher during the early follow-up period and should decline thereafter.Methods: We tested this hypothesis by estimating the relative risk of death from prostate cancer in the National Health and Nutrition Examination Survey III for incremental increases in total and ionized serum calcium using Cox proportional hazards regression with time-dependent effects.Results: Forty-nine (49) fatal prostate cancers occurred over 204 months of follow-up and 1,069,327 person-months of observation. Men with higher total serum calcium and higher serum ionized calcium had increased risks of fatal prostate cancer during the first 96 months of follow-up [Relative Hazard (RH) ¼ 1.50 per 0.1 mmol/L total serum calcium, 95% confidence interval (CI) ¼ 1.04-2.17; RH ¼ 1.72 per 0.05 mmol/L ionized calcium, 95% CI ¼ 1.11-2.66]. Evidence of an association between total and ionized serum calcium and prostate cancer deaths was not significant after 96 months.Conclusions: Our analyses support the hypothesis that the elevated risk for fatal prostate cancer observed in men with high serum calcium is because of the presence of extant, but occult prostate cancer.Impact: These findings have implications for the potential use of serum calcium in the detection of clinically significant prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(10); 1768-73. Ó2012 AACR.

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“…9 In patients with prostate cancer this metabolic disturbance has been described exceptionally. [10][11][12][13] A number of factors could prevent the onset of hypercalcemia in prostate cancer patients. The osteoblastic nature of bone lesions could lead to calcium entrapment in bone.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 Few papers, which are case reports or series of symptomatic cases, reported data on hypercalcemia in patients with prostate cancer. [10][11][12][13] To our knowledge no data are available on prevalence of supranormal calcium levels in advanced prostate cancer population. The prevalence of hypocalcemia in bone metastatic prostate cancer patients has been reported in one study showing that 43 of 131 patients (33%) had calcium levels below the normal range.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

Tucci

Mosca

Lamanna

et al. 2008

Prostate Cancer Prostatic Dis

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Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients. The presence of hypocalcemia and hypercalcemia was related with baseline biochemical and clinical characteristics and the role of these two calcium disturbances in predicting prognosis and adverse skeletal-related events (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients (n ¼ 51) had higher tumor load in bone (P ¼ 0.005), higher plasma chromogranin A (CgA, P ¼ 0.01), serum alkaline phosphatase (P ¼ 0.01), urinary N-telopeptide (NTX, P ¼ 0.002) and lower hemoglobin values (P ¼ 0.01), while hypercalcemic patients (n ¼ 16) had higher plasma CgA (P ¼ 0.001) and serum lactate dehydrogenase values (P ¼ 0.001), higher bone pain (P ¼ 0.003) and a lower frequency of pure osteoblastic lesions (P ¼ 0.001). Hypercalcemia was significantly associated with poor prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2-3.3) and higher risk to develop SREs HR, 2.5 (95% CI 1.2-5.2, P ¼ 0.01), while hypocalcemia was not associated with poor prognosis. The prognostic role of hypercalcemia was maintained in multivariate analysis after adjusting for validated prognostic parameters: HR, 2.72 (95% CI 1.1-6.8, P ¼ 0.03). These data suggest that serum calcium levels should be taken into account in the clinical decision-making process of bone metastatic prostate cancer patients. Patients with asymptomatic hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate treatment. Further prospective clinical trials are needed to confirm this finding.

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Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature.

Abstract: Hypercalcemia in the setting of prostate cancer should prompt a search for unusual histologies.

Cited by 49 publications

References 41 publications

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL

A Prospective Study of Total and Ionized Serum Calcium and Time to Fatal Prostate Cancer

Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

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