The outcome of prostate cancer patients treated with curative intent strongly depends on survival after metastatic progression.

BACKGROUND: Five-year survival in patients with localized prostate cancer (PCa) is nearly 100%, but metastatic disease still remains incurable. Clinical management of metastatic patients has become increasingly complex as novel therapeutic strategies have emerged. This study aims at evaluating the impact of the first metastatic progression on the outcome of PCa patients treated with curative intent. METHODS: The analysis was conducted using data of 913 cases of localized PCa diagnosed between 2000 and 2014. All patients were treated with curative surgery (N = 382) or radiotherapy (N = 531) with or without adjuvant therapy. All metastases were radiologically documented. The prognostic impact of the first site of metastasis on metastasis-free survival (MFS) and PCa-specific survival (PCaSS) was investigated by univariate and multivariate analyses. RESULTS: One hundred and thirty-six (14.9%) patients developed a metastatic hormone-sensitive PCa and had a median PCaSS of 50.4 months after first metastatic progression. Bone (N = 50, 36.8%) and LN or locoregional (N = 52, 38.2%) metastases occurred more frequently with a median PCaSS of 39.7 and 137 months respectively (p < 0.0001). Seven patients developed visceral metastasis only (5.1%; liver, lung, brain) and 27 (19.9%) concurrent metastases; this last group was associated with the worst survival with a median value of only 17 months. Thus, each subgroup exhibited a survival after metastasis significantly different from each other. In multivariate analysis the site of the first metastasis was an independent prognostic factor for PCaSS along with Gleason score at diagnosis. The correlation between survival and first site of metastasis was confirmed separately for each therapy subgroup. Median metastasis-free survival from primary diagnosis to first metastasis was not correlated with the first site of metastasis. CONCLUSIONS: In non-metastatic PCa patients treated with curative intent, the PCa-specific survival time depends on the time after metastatic progression rather than the time from diagnosis to metastasis. Moreover, the site of first metastasis is an independent prognostic factor for PCaSS. Our data confirm that the first metastatic event may confer a differential prognostic impact and may help in identifying patient at high risk of death supporting the treatment-decision making process following metastatic progression.

The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients.

BACKGROUND: Neuroendocrine markers, which could indicate for aggressive variants of prostate cancer and Ki67 (a well-known marker in oncology for defining tumor proliferation), have already been associated with clinical outcome in prostate cancer. The aim of this study was to investigate the prognostic value of those markers in primary prostate cancer patients. PATIENTS AND METHODS: NSE (neuron specific enolase), ChrA (chromogranin A), Syp (Synaptophysin) and Ki67 staining were performed by immunohistochemistry. Then, the prognostic impact of their expression on overall survival was investigated in 166 primary prostate cancer patients by univariate and multivariate analyses. RESULTS: NSE, ChrA, Syp and Ki67 were positive in 50, 45, 54 and 146 out of 166 patients, respectively. In Kaplan-Meier analysis only diffuse NSE staining (negative vs diffuse, p = 0.004) and Ki67 (≤ 10% vs > 10%, p < 0.0001) were significantly associated with overall survival. Ki67 expression, but not NSE, resulted as an independent prognostic factor for overall survival in multivariate analysis. CONCLUSIONS: A prognostic model incorporating Ki67 expression with clinical-pathological covariates could provide additional prognostic information. Ki67 may thus improve prediction of prostate cancer outcome based on standard clinical-pathological parameters improving prognosis and management of prostate cancer patients.

Is human papillomavirus associated with prostate cancer survival?

The role of human papillomavirus (HPV) in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa), whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67%) patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS) (median 4.59 years) compared to HPV-negative (median 8.24 years, P = 0.0381). In multivariate analysis age (P < 0.001), Gleason score (P < 0.001), nuclear grading (P = 0.002), and HPV status (P = 0.034) were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.