Andrzej Antczak

BRCA1 mutations and prostate cancer in Poland

Evidence to date that BRCA1 mutation carriers are at an increased risk of prostate cancer is mixed – both positive and negative studies have been published. To establish whether or not inherited variation in BRCA1 influences prostate cancer risk we genotyped 1793 men with prostate cancer in Poland and 4570 controls for three founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.45% of the cases and 0.48% of the controls (odds ratio=0.9; P=1.0). The odds ratios varied substantially by mutation. The 5382insC mutation is the most common of the three founder mutations. It was detected only in one case (0.06%), whereas it was seen in 0.37% of controls (P=0.06). In contrast, the 4153delA was more common in prostate cancer cases (0.22%) than in controls (0.04%) (odds ratio=5.1; 95% confidence interval: 0.9–27.9; P=0.1). The C61G mutation was also found in excess in cases (0.17%) compared with controls (0.07%) (odds ratio=2.6; 95% confidence interval: 0.5–12.7; P=0.5). Eight men with prostate cancer carried a mutation. Only one of these carried the 5382insC mutation, compared with 17 of 22 individuals with mutations in the control population (P=0.003). These data suggest that the 5382insC mutation is unlikely to be pathogenic for prostate cancer in the Polish population. The presence of one of the other alleles was associated with an increased risk for prostate cancer (odds ratio=3.6; 95% confidence interval: 1.1–11.3; P=0.045); in particular for familial prostate cancer (odds ratio=12; 95% confidence interval: 2.9–51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers varies with the position of the mutation.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland

The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20‐fold). The geographical and ethnic extent of this recurrent allele has not yet been determined.

Benefit of Whole Pelvic Radiotherapy Combined with Neoadjuvant Androgen Deprivation for the High-Risk Prostate Cancer

Aim. To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only. Material and Methods. Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts. Results. The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively. Conclusions. The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed.

Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

Androgen-deprivation therapy (ADT) is used routinely in combination with definitive external beam radiation therapy (EBRT) in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT) also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.

A common nonsense mutation of the BLM gene and prostate cancer risk and survival

BACKGROUND Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis. Mutations of the BLM gene cause another chromosomal instability clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating mutation of BLM (Q548X) has been associated with a 6-fold increased risk of breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer etiology and survival has not been investigated yet. METHODS To establish whether the Q548X allele of the BLM gene is present in Poland, and whether this allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with prostate cancer and 2604 controls. RESULTS Q548X was detected in 13 of 3337 (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7; 95% CI 0.3-1.4). A positive family history of any cancer in a first- or second-degree relative was seen only in 4 of the 13 (30%) mutation positive families, compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow-up was 49months. Survival was similar among carriers of Q548X and non-carriers (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%, compared to 72% for mutation-negative cases. CONCLUSIONS BLM Q548X is a common founder mutation in Poland. We found no evidence that this mutation predisposes one to prostate cancer or affect prostate cancer survival. However, based on the observed 0.6% population frequency of the Q548X allele, we estimate that one in 100,000 children should be affected by Bloom syndrome in Poland.

Predictions of cancer incidence in Poland in 2019

IntroductionThe future burden of cancer can be quantify from two different perspectives: the number of new cancer cases and age-standardized rates.GoalMaking prognosis of number of cancer cases in Poland in 2019.MethodologyThese predictions of number of cancer cases in 2019 has been based on the historical trends of cancer incidence in Poland in 2000–2009 and the demographical prognosis made by Central Statistical Office using the method of Hakulinen and Dyba.ResultsThere will be 76 629 new cancer cases in men and 75 815 cases in women in 2019. Compare to the period 2005–2009 the number of cancer cases in Poland will increase by 25.1% for men and by 26.1% for women. In 2019 the increase in number of colorectal cancer cases for both sexes, lung, breast and endometrial cancer for women and prostate cancer for men will be observed. For stomach cancer for both sexes, cervical cancer in women and lung cancer in men the predicted number of cases will decrease.ConclusionsThe predicted increase in cancer incidence for Poland in 2019 will be the results of: the demographical changes, the influence of the cancer risk factors and the participation in the screening programs.

Predictions of cancer incidence in Wielkopolska in 2018

Aim of the study The cancer incidence in Wielkopolska in 2008 was one of the highest in the country and was higher than in Poland by 21% in men and by 14% in women. We can quantify the future burden of cancer from two different perspectives: the number of new cancer cases due to population change and new cases due to risk change. Making predictions of number of new cancer cases in Wielkopolska in 2018. Material and methods These projections of number of cancer cases, age specific rates and age-standardized rates for 2018 (all cancers and the most frequent cancers for men and women) has been based on the historical trends of cancer incidence in Wielkopolska in 1999-2008 and demographical prognosis of Central Statistical Office using the method of Hakulinen and Dyba. Results There will be over 8000 new cancer cases in men in Wielkopolska in 2018 and over 7000 in women. Compare to the period 2004-2008 the number of cancer cases will increase by 45% for men and by nearly 30% for women. About 2/3 of the increase in Wielkopolska is predicted to be connected with demography change, 1/3 with risk change. Conclusions The predicted increase of number of cancer cases in Wielkopolska in 2018 will be the result of: changes in the population (bigger impact of the older age groups), an influence of the risk factors (mainly smoking) and a participation in the screening programs.

The presence of prostate cancer at biopsy is predicted by a number of genetic variants

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low‐risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.

Hormone therapy in combination with radiotherapy in the treatment of prostate cancer: why and in which group of patients?

In recent years, significant development in the treatment of prostate cancer has taken place. One of the most documented methods of treatment in patients characterised by a high risk of progression is a combination of radiotherapy (RT) with long-term hormone therapy (HT). In this group of patients, neither RT alone nor HT alone allows satisfactory outcomes to be achieved, and therefore as monotherapy they are not recommended as optimal methods of treatment. In this review, we summarise arguments for combining radiotherapy with hormonal therapy in high-risk prostate cancer, with an emphasis on the results of phase III trials.

What is the possible role of PSA doubling time (PSADT) and PSA velocity (PSAV) in the decision-making process to initiate salvage radiotherapy following radical prostatectomy in patients with prostate cancer?

This article is an attempt to present a contemporary view on the role of the kinetics of PSA levels as defined by PSA doubling time (PSADT) and PSA velocity (PSAV) in the decision-making process to initiate salvage radiotherapy in patients with prostate cancer after radical prostatectomy (RP). The dynamics of the rise of PSA levels may be an early endpoint parameter, preceding the diagnosis of distant metastasis or death due to prostate cancer based on a single PSA determination. Thus, it seems reasonable to include the kinetics of PSA levels, apart from single PSA determination, in the decision-making algorithm. In a group of patients after RP, PSADT might be an early endpoint that could replace cause-specific survival rate as a late endpoint. PSADT allows distinguishing subgroups of patients at high risk of distant metastases and death, which in turn may lead to a change in the further treatment strategy. Therefore, patients with short PSA doubling time should become a subgroup, in which hormonal therapy should be considered. To date, there is no unanimous consent to accept the criteria of assessment of the dynamics of PSA levels as determinants of treatment in case of recurrences following RP. However, a number of non-randomized clinical trials in patients after RP suggest it would be useful to include these parameters in the decision-making process. For instance, a relationship was found between increased PSA velocity (>2 ng/mL/year) before initiation of oncological treatment and increased (12-fold) risk of death. A number of well-documented retrospective analyses show that PSADT is one of the most important parameters to describe the disease aggressiveness. It has to be stressed that single determination of PSA levels is much less precise in terms of describing the biological aggressiveness of prostate cancer than PSADT. Of course, the question regarding the need to include the PSA levels kinetic parameters as crucial elements of patient management algorithms can be answered in a definitive manner only by randomized clinical trials.