Advanced approach for screening soil with a low radiocesium transfer to brown rice in Fukushima based on exchangeable and nonexchangeable potassium.

Phytoavailable K in soil is a key to control the transfer factor of radiocesium from soil to brown rice. The transfer factors were determined for paddy fields cultivated in 2017 and 2018 under different K fertilization regimes in Fukushima Prefecture, Japan. Two phytoavailable forms of K, the exchangeable and nonexchangeable K contents were investigated for the surface soil sampled after the transplanting and fertilization as well as after harvest of rice in the same paddy fields. The exchangeable K content largely decreased from after transplanting and fertilization to after harvest, and the exchangeable K of the soil after harvest was negatively correlated with the transfer factor (rs = -0.70, p < .001). Most soil samples after harvest showed that the transfer factors exponentially increased as the exchangeable K decreased; however, some of the samples indicated considerably low transfer factors (<0.005) despite being exchangeable K deficient, i.e., exchangeable K < 25 mg K2O 100 g-1. Even though this value before usual fertilization has been effectively used as a threshold to determine whether supplemental K fertilization is required to reduce the radiocesium content in brown rice, additional screening was needed to estimate this radiocesium transfer more precisely. Thus, we found that not only the exchangeable K but also nonexchangeable K contents had a negative correlation with the transfer factor (rs = -0.60, p < .001) of the soil samples after harvest but were not correlated with each other (rp = -0.10). Furthermore, the results revealed that soil with nonexchangeable K > 50 mg K2O 100 g-1 indicated a considerably low transfer factor, even if exchangeable K deficient. Thus, via our field-scale experiments, we concluded that the criterion nonexchangeable K > 50 mg K2O 100 g-1 can be used as another threshold for use along with that of exchangeable K to differentiate soil with a low radiocesium transfer rate from exchangeable K deficient soil.

[Cae of double cancer involving of the bladder and prostate which was treated by radical cystectomy 8 years after radical prostatectomy].

A 66-year-old man was diagnosed as having prostate cancer (T2aN0M0) and neoadjuvant hormone therapy was started from 17 February 1995. During observation, superficial bladder cancer was incidentally found and the first transurethral resection was carried out on 21 June 1995. Radical prostatectomy was performed on 8 May 1996. Thereafter, bladder cancer demonstrated repeated recurrence. At the time of the third recurrence, malignant trasformation was recognized as TCC G3 T2 or more invasive, and radical cystectomy with ileal conduit was performed on 12 May 2004 when the patient was 74 years old. From the perspective of double cancer, the frequency of diagnosing localized prostate cancer with superficial bladder cancer is expected to increase because PSA screening is being increasingly performed recently. Because of the possibility of malignant transformation in patients with superficial bladder cancer, in cases of coincident of cancers, it remains controversial which treatment should be selected for the previously diagnosed prostate cancer. Here, we report the clinical course and discuss this issue to some extent.

MR spectroscopy as a reliable diagnostic tool for localization of prostate cancer.

BACKGROUND: Magnetic resonance spectroscopy (MRS) is a new diagnostic tool which allows the detection of cellular metabolites. We assessed the usefulness of single- voxel MRS diagnosis for localization of prostate cancer. PATIENTS AND METHODS: The study population consisted of 10 patients with prostate cancer. We set I or 2 voxels at the peripheral zone (PZ) of the prostate where biopsy had confirmed adenocarcinoma. MRS provided metabolic information about citrate, creatine and choline levels. We calculated the ratio of these metabolites ([choline + creatine]/citrate) and judged areas where the metabolic ratio was greater than 0.86 as positive. RESULTS: Thirteen out of 19 voxels showed a cancer pattern which indicated a high choline peak and low citrate peak The accuracy, sensitivity and specificity of MRS diagnosis of tumor localization were 84.2%, 81.3% and 100%, respectively. CONCLUSION: MRS is useful for the diagnosis of prostate cancer localization.

The combination of multi-voxel MR spectroscopy with MR imaging improve the diagnostic accuracy for localization of prostate cancer.

BACKGROUND: We assessed the usefulness of combined multi-voxel magnetic resonance spectroscopy (MRS) and MR imaging (MRI) in the diagnosis of prostate cancer localization. PATIENTS AND METHODS: MRS and MRI were performed in 21 patients with prostate cancer. On T2-weighted images, tumor localization was based on low signal intensity in the peripheral zone. At MRS, cancer patterns were diagnosed when the ratio of choline plus creatine to citrate was greater than 0.86. The results were analyzed with reference to pathological confirmation of prostate cancer at bilateral or unilateral lobe. RESULTS: Six out of 11 patients with unilateral positive biopsy specimens were diagnosed as unilateral cancer, and 9 of 10 patients with bilateral positive biopsy specimens were diagnosed as bilateral cancer on MRI. Two of 4 patients with unilateral cancer, who were not detected on MRI alone, were diagnosed as unilateral cancer on combined MRI and MRS. The accuracy of MRI alone was 71.4%, while that of combined MRI and MRS was 81.0%. CONCLUSION: Combined MRI and MRS improved the diagnostic accuracy for localization of prostate cancer.

Association of genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) with familial prostate cancer risk in a Japanese population.

BACKGROUND: Glutathione-S-transferases (GSTs) are active in the detoxification of a wide variety of toxins and carcinogens. The genetic polymorphisms of GSTM1, GSTT1 and GSTP1 genes have been studied to estimate the relative risk of various cancers. In the current study, we examined the association of the GST gene polymorphisms with familial prostate cancer in a Japanese population by performing a case-control study consisting of 81 familial prostate cancer cases and 105 normal controls. MATERIALS AND METHODS: No significant association of the GSTM1 and GSTT1 gene polymorphisms with familial prostate cancer risk was found; however, the Val/Val genotype of the GSTP1 gene significantly increased risk (OR = 9.31, 95% CI = 0.47-184, p = 0.030). The combination analysis of genotypes of the three genes showed that presence of two high-risk genotypes, i.e., null genotype of the GSTM1 or GSTT1 gene, or any Val genotypes of the GSP1 gene, significantly increased the risk of prostate cancer (OR = 2.67, 95% CI = 1.08-6.59, p = 0.03). Stratification of cases according to the pathological grade or the clinical stage showed no significant differences among categories. CONCLUSION: In the present study, we found that genotypes of GSTs, especially the Val-allele of the GSTP1 gene and the combination of three genotypes, were associated with familial prostate cancer risk.

Association of HPC2/ELAC2 polymorphism with prostate cancer risk in a Japanese population.

BACKGROUND: To investigate the relationship between two common variants (Ser217 and Ala541) of the HPC2/ELAC2 gene and prostate cancer risk in a Japanese population, we performed a case-control study. MATERIALS AND METHODS: Cases and controls consisted of 81 prostate cancer patients with a family history and 106 controls. Ser217 and Ala541 polymorphisms were analyzed by the restriction fragment length polymorphism method. RESULTS: In controls, 94.5% and 100.0% had wild-type Ser217Ser and Ala541Ala genotypes, respectively. 5.7% of the controls had the Leu217 genotype. No Thr541 genotype was observed in the controls. 92.6% and 97.5% of the cases had the Ser217Ser and Ala541Ala genotypes. No significant differences were observed in the genotypic frequencies between controls and cases. We stratified prostate cancer cases according to the pathological grade (low- or high-grade) or the clinical stage (localized or metastatic). There was no statistical difference between the genotypic frequencies between the groups. CONCLUSION: The present study suggested that the common variants in the HPC2/ELAC2 gene play a limited role in the risk of prostate cancer in the Japanese population.

[Treatment strategy for locally advanced prostate cancer].

With the increasing aged population, prostate cancer has become one of the commonest malignant tumors in the United States. The incidence of prostate cancer is the highest among malignant tumors in males, and the mortality rate is the second highest following lung cancer. Even when prostate cancer is diagnosed to be in the early stage preoperatively, its excised lesions are often judged pathohistologically to be locally advanced tumor (staging error). Therefore, to estimate the exact pathological stage of excised lesions by preoperative parameters such as clinical T, PSA and biopsy Gleason Score, Partin's nomogram is generally used in the United States. However, according to the annual update version of the 2001 millennium update, radical prostatectomy should not be applied to T3, and it was excluded from the nomogram. Currently, the standard methods for the treatment of locally advanced prostate cancer may be external beam radiotherapy and brachytherapy with neoadjuvant hormonal therapy and intraprostate 125I and 103Pd seeds with neoadjuvant hormonal therapy, although the long-term results are unknown. In our study, similar to a report by Messing et al., adjuvant hormonal therapy might be effective in patients in whom the tumor was diagnosed as being in the early stage but was later found to be N (+) after its operation.

Pelvic autonomic nerve mapping around the prostate by intraoperative electrical stimulation with simultaneous measurement of intracavernous and intraurethral pressure.

PURPOSE: In previous studies we noted that the neurovascular bundle was not identical to the bundle of the cavernous nerve fibers. In this study we sought to prove these anatomical findings electrophysiologically and map the autonomic nerve fibers by intraoperative simultaneous measurement of intracavernous pressure and intraurethral pressure. MATERIALS AND METHODS: Between January 2004 and May 2005 electrical stimulation was performed in 27 open pelvic surgeries, including 26 radical retropubic prostatectomies and 1 radical cystectomy, using an original bipolar electrode before prostate removal. Nerve stimulation was performed at the base of the so-called neurovascular bundle (point A) and the rectal wall about 1 cm posterolateral, apart from the neurovascular bundle (point B). Intracavernous pressure and intraurethral pressure were measured simultaneously. RESULTS: The mean +/- SD increase in intracavernous pressure was 9.8 +/- 6.3 cm H2O at point A and 13.5 +/- 7.3 cm H2O at point B. Intracavernous pressure at point B was significantly higher than at point A (p = 0.0240). The mean increase in intraurethral pressure was 17.0 +/- 9.4 cm H2O at point A and 11.2 +/- 8.1 cm H2O at point B. Intraurethral pressure at point A was significantly higher than at point B (p = 0.0353). CONCLUSIONS: The course of the cavernous nerves did not always agree with the surgically identified neurovascular bundle. The distribution of cavernous nerves was wider than our image of the neurovascular bundle and it existed on the rectal wall posterolateral, apart from the neurovascular bundle rather than the neurovascular bundle itself. The surgically identified neurovascular bundle contained the nerve fibers contributing to urinary continence.

Peritoneal recurrence of gastric cancer with mucin phenotype 12 years after curative resection: report of a case.

We report a case of peritoneal recurrence of gastric cancer in a 58-year-old man, 12 years after curative surgery. Urinary wall thickness was seen on follow-up computed tomography and magnetic resonance imaging scans. We performed total nephroureterectomy and cystectomy for urinary tract cancers, but histological examination of the resected specimen revealed poorly differentiated adenocarcinoma with severe fibrosis, resembling the gastric cancer resected 12 years earlier. Immunohistological examination revealed human gastric mucin (45M1) and intestinal mucin (MUC2) phenotype in both the original gastric cancers and the urinary tract cancers. Thus, we concluded that the second cancer was a peritoneal recurrence of gastric cancer with gastric and intestinal mucin phenotypes. Although peritoneal recurrence so many years after curative gastrectomy is rare, careful long-term follow-up should be done for all patients undergoing surgery for gastric cancer with mucin phenotype.

Clinical validity of proliferating cell nuclear antigen as an objective marker for evaluating biologic features in patients with untreated prostate cancer.

BACKGROUND: Although Gleason grading may be the most useful system for evaluating biological activity of untreated prostate cancer, lack of interobserver validity with Gleason scores (GS) is an unsolved issue. In this study, the proliferating cell nuclear antigen labeling index (PCNA LI) in untreated prostate cancer was investigated in order to clarify the usefulness of supplemental and objective markers for evaluating the biologic features of prostate cancer. METHODS: Sixty cases of prostate cancer were randomly selected from the cancer registry in Gunma University Hospital for this study. PCNA LI were evaluated using paraffin-embedded biopsy cores taken at diagnosis. Correlation of PCNA LI with the Gleason grading system, clinical stage, serum prostate-specific antigen (PSA) levels and age were evaluated. Cumulative rates of freedom from cause-specific death were also evaluated stratified by various clinicopathologic features, including PCNA LI using Kaplan-Meier analysis. RESULTS: Proliferating cell nuclear antigen labeling index was significantly higher in patients with PSA levels over 100 ng/mL, advanced clinical stage (>T4, N1 or M1 disease), higher Gleason grade or with a higher GS than in those with other clinicopathologic features. The 5-year cumulative rate of death from prostate cancer was significantly higher at 62% in patients with a PCNA LI of 20 or more than those with PCNA LI of less than 20, who accounted for 4%. CONCLUSIONS: Proliferating cell nuclear antigen labeling index in combination with Gleason grading system may be of clinical value in evaluating biologic features and also in predicting cause specific survival of prostate cancer in an objective, reliable and reproducible manner.

Significance of electrostimulation in detecting neurovascular bundle during radical prostatectomy.

OBJECTIVE: The reported rate of erectile dysfunction after nerve-sparing prostatectomy varies according to physicians. Because exact preservation of the neurovascular bundle (NVB) solely depends on the judgment of the physician, he or she should try to correctly identify the NVB and also avoid neurophysiologic injury of the NVB during the procedure. The purpose of the present study is to assess the status of the NVB preservation by physician's judgment at the operation, the changes in intracavernous pressure related to intraoperative electrical stimulation and postoperative histopathological examination. PATIENTS AND METHODS: Thirty-eight patients who underwent nerve-sparing radical prostatectomy judged by intraoperative electrical stimulation of the NVB were included in this study. Bilateral, unilateral and non-nerve-sparing procedures were performed in 18, 17, and 3 cases, respectively. The NVB preservation evaluated by intraoperative physician's judgment was compared to that evaluated by postoperative histopathological examination. Furthermore, the NVB preservation evaluated by intraoperative electrical stimulation was compared to that by physician's judgment and postoperative histopathological examination. RESULTS: For 68 of 76 NVB (89.5%), intraoperative subjective judgment and histopathological assessment were identical. For 66 of 76 NVB (86.8%), electrical stimulation findings and the physician's judgments were identical, and for 70 of 76 NVB (92.1%), electrical stimulation findings and histopathological findings were identical. CONCLUSION: Even if physicians are convinced of a successful nerve-sparing procedure, there are some cases in which the NVB is not preserved accurately or neurophysiological damage is suffered. Therefore, intraoperative electrical stimulation of the NVB as well as the cavernosal nerve is very useful in evaluation of NVB preservation.

A comparison of interobserver reproducibility of Gleason grading of prostatic carcinoma in Japan and the United States.

CONTEXT: Gleason grading is now the sole prostatic carcinoma grading system recommended by the World Health Organization. It is imperative that there be good interobserver reproducibility within this system worldwide. To our knowledge, there are no studies, using the same specimens, that compare the interobserver reproducibility of Gleason grading in Japan and the United States. OBJECTIVE: To compare the interobserver reproducibility of Gleason grading of prostatic carcinoma in Japan and the United States using, in Japan, images from the identical biopsy glass slides that were originally graded in the United States. DESIGN: Microsopic images from 37 needle biopsies of prostatic carcinoma were placed on CD-ROM and distributed to 14 Japanese pathologists for grading. These 14 physicians included 8 general pathologists and 6 pathologists with a special interest in urologic pathology. The needle biopsies had been previously reviewed so that a consensus diagnosis could be formed by a panel of urologic pathologists in the United States and Canada. Interobserver agreement with the consensus diagnoses was calculated by determining the overall kappa coefficient for the Japanese pathologists and then compared to the interobserver agreement among American general pathologists who had previously graded identical needle biopsies from which the CD-ROM images had been taken. RESULTS: The interobserver agreement with the consensus diagnoses for the 4 Gleason grading groups (Gleason grades 2-4, 5-6, 7, and 8-10) among the Japanese urologic pathologists in this series of cases was substantial (overall kappa = 0.68), and for the Japanese general pathologists, it was moderate (overall kappa = 0.49), similar to that reported in the earlier study of American general pathologists (overall kappa = 0.44). The major interobserver reproducibility problem for both Japanese and American general pathologists is undergrading. The major areas of undergrading are the underdiagnosis of Gleason scores 5-6 as Gleason scores 2-4, and the underdiagnosis of cribriform sheets and fragments of cribriform Gleason pattern 4 carcinoma as Gleason pattern 3. CONCLUSIONS: The interobserver reproducibility of the Gleason grading for this collection of specimens was similar among Japanese and American general pathologists. The overall kappa values for these generalists of 0.44 and 0.49 are only in the moderate (0.41-0.60) range of interobserver agreement when compared to 0.68, substantial (0.61-0.80) agreement, for Japanese urologic pathologists. Educational efforts to improve Gleason grading have been shown to be effective and are clearly warranted.

Salvage external beam radiotherapy for local recurrence without systemic progression or prostate specific antigen recurrence of prostate cancer after initial hormonal therapy: is it possible to identify patients likely to have good treatment outcomes?

BACKGROUND: We attempted to identify factors that predict the outcomes of salvage external beam radiotherapy (sEBRT) in patients who showed local recurrence without systemic progression or isolated prostate specific antigen (PSA) recurrence after initial hormonal therapy. METHODS: The subjects were 33 patients who were diagnosed as having local recurrence without systemic progression (30 cases) or isolated PSA recurrence (three cases). Of these patients, those with continuously decreasing PSA levels, which were 1.0 ng/ml or less 1-1.5 years after sEBRT, were regarded as good responders (GR) whereas the remaining patients were regarded as poor responders (nGR). Survival rates in these patients and factors that distinguish GR from nGR were evaluated retrospectively. RESULTS: The cancer-specific 10-year survival rate was 82.4% in the 33 patients, 100% in the 21 GR patients and 55% in the 12 nGR patients (P < 0.0001). Stepwise variable selection to discriminate between GR and nGR revealed that the time from sEBRT initiation to the nadir PSA was the most significant factor (P = 0.000097). Before sEBRT, GR can be predicted in patients with pre-sEBRT PSA <30.0 ng/ml and PSA doubling time (PSADT) >7.0 months, with a sensitivity of 95.2% (20/21), a specificity of 100% and an accuracy of 97.0%. CONCLUSION: Good responses to sEBRT can be expected in patients with local recurrence without systemic progression or isolated PSA recurrence after initial hormonal therapy when the patients show both pre-sEBRT PSA <30.0 ng/ml and PSADT >7.0 months.

Usefulness of PSA screening in outpatients with bladder cancer: preliminary results.

BACKGROUND: We performed prostate-specific antigen (PSA) screening and evaluated its usefulness in outpatients with bladder cancer who may have an elevated risk for prostate cancer. METHODS: Sixty-one new or followed-up outpatients with bladder cancer were examined between September 1999 and December 2000 in the Department of Urology, Gunma University Hospital, Japan. PSA was measured after informed consent was obtained, and patients in whom the PSA level was 4.1 ng/mL or higher were selected for thorough examination. In the examination, one examiner performed DRE (digital rectal examination) and, based on DRE and TRUS (transrectal ultrasonography) findings, determined whether prostate biopsy was indicated. RESULTS: The average age of the 61 cases was 69.1 +/- 8.6 years, and the average PSA level was 3.5 +/- 5.8 ng/mL. The PSA level was 4.1 ng/mL or higher in 11 (18.0%) patients, nine of whom underwent six-sextant biopsy under TRUS guidance. Of these nine cases, four (6.6%) were diagnosed as having prostate cancer. The Gleason score was 7 in three cases and 9 in one case. The clinical stage was T2N0M0 in three cases and T3N0M0 in one case. CONCLUSIONS: On PSA screening in patients with bladder cancer and patients with a history of transurethral resection of the bladder tumor (TUR-BT), prostate cancer was found in 6.6%. This rate is higher than in the general population. These cancers were classified into intermediate to high-risk groups, and the prognosis of prostate cancers could be more important than those of the bladder cancers in two cases (50%). We conclude that PSA screening for inpatients with bladder cancer may be useful.

The risk of rapid prostate specific antigen increase in men with baseline prostate specific antigen 2.0 ng/ml or less.

PURPOSE: We estimated the risk of a rapid prostate specific antigen (PSA) increase in men with a low baseline PSA range of 0.0 to 2.0 ng/ml to investigate the validity of setting a re-screening interval of more than 1 year. MATERIALS AND METHODS: Between 1988 and 1999, 6,252 men with baseline PSA 2.0 ng/ml or less without suspicious findings on digital rectal examination (DRE) and 7,304 with the same baseline PSA who did not undergo DRE at the time of baseline PSA measurement were re-screened. The risks of a PSA increase to 4.1 to 10.0, 10.1 to 20.0 and greater than 20.0 ng/ml were investigated and stratified by re-screening interval, baseline DRE status, and subdivided baseline PSA ranges of 0.0 to 1.0 and 1.1 to 2.0 ng/ml. RESULTS: A total of 28 cases (0.2% of 13,556) of prostate cancer were detected after an average re-screening interval of 3.6 years. High PSA above 10 ng/ml at diagnosis was noted in 5 patients (18%), including 2 with a great PSA increase to 1,928 and 298 ng/ml at re-screening intervals of 4 and 6 years, respectively. CONCLUSIONS: Setting 4 to 5-year re-screening intervals for PSA measurements in men with PSA 1.0 ng/ml or less can decrease the cost of PSA tests without lowering sensitivity. A re-screening interval for PSA measurement should be set annually for men with PSA 1.1 to 2.0 ng/ml to minimize the risk of missing aggressive cancer.

Incidence of bladder cancer discovered by urethrocystoscopy at prostate biopsy: extraordinary high incidence of tiny bladder cancer in elderly males.

In order to clarify the incidence of bladder cancer with and without prostate cancer, we investigated bladder cancer discovered incidentally by urethrocystoscopy at prostate biopsy. Between April 1997 and December 2003, 498 patients who were suspected prostate cancer were performed prostate biopsy and urethrocystoscopy simultaneously. We investigate possible invasion of prostate cancer into the urethra or bladder mucosa as well as bladder cancer, including other benign lesions of the bladder by urethrocystoscopy. Prostate cancer was confirmed in 175 (35.1%) of the 498 patients histologically, and bladder cancer was discovered incidentally in 12 patients (2.4 %). The incidence of bladder cancer in patients with prostate cancer of 2.3% (4/175) was not significantly different from that in patients without prostate cancer, which was 2.5% (8/323). Superficial and those with a size less than 1 cm were noted in 11 patients (92%) and 10 patients (83%) respectively. High incidence rate of bladder cancer with prostate cancer was reported previously, however, there was no study to compare the incidence rate of bladder cancer between cases with and without prostate cancer. The present study suggests that asymptomatic tiny bladder cancer may be present at an unexpectedly high incidence rate in elderly males.

Electrostimulation of sympathetic nerve fibers during nerve-sparing laparoscopic retroperitoneal lymph node dissection in testicular tumor.

A long-handled pair of electrodes with sufficient length to allow stimulation during laparoscopic retroperitoneal lymph node dissection (RPLND) was designed at our institute. We clinically utilized this electrode in the treatment of a 37-year-old patient with testicular tumor who underwent right orchidectomy and nerve-sparing laparoscopic RPLND. During laparoscopic RPLND, sympathetic nerve fibers relevant to ejaculation were electrically stimulated and changes in pressure at the bladder neck were observed. Nerve preservation was confirmed by increased pressure at the bladder neck and ejaculation immediately after the electrostimulation. The application of laparoscopic electrostimulation may become widespread, particularly since it meets the increasing demand for minimally invasive surgery.

Free/total PSA ratio is a powerful predictor of future prostate cancer morbidity in men with initial PSA levels of 4.1 to 10.0 ng/mL.

OBJECTIVES: To evaluate the usefulness of measuring the free/total prostate-specific antigen (PSA) ratio (%fPSA) in men with initial PSA levels of 4.1 to 10.0 ng/mL as a predictor of the future risk of developing prostate cancer. METHODS: Between 1989 and 2001, 201 subjects with an initial PSA level of 4.1 to 10.0 ng/mL, who had free PSA measured at initial screening using frozen serum and underwent consecutive screening at least once, were enrolled in this study. All participants were followed up by consecutive PSA measurements. Biopsies were performed for those with PSA levels greater than 10.0 ng/mL or with a PSA velocity of 1.0 ng/mL or greater in consecutive screening. The follow-up period was 1 to 12 years, and the mean number of screenings was 3.8. The usefulness of %fPSA, age, and total PSA as predictive factors of future prostate cancer morbidity was investigated. The cumulative non-prostate cancer rate was evaluated using Kaplan-Meier analysis relative to various %fPSA cutoffs. RESULTS: A total of 142 patients (71%) underwent prostate biopsy at least once during observation according to the biopsy criteria. The detection rate of prostate cancer was 26% (53 of 201) in consecutive screening. The most recent PSA velocity and serum PSA levels at last follow-up in patients with prostate cancer were significantly higher than in those without prostate cancer. The cumulative non-prostate cancer rate was significantly greater in subjects with %fPSA less than the cutoff than in those with %fPSA at the cutoff point or greater in the %fPSA cutoffs of 16% to 25%. CONCLUSIONS: Men with PSA levels of 4.1 to 10 ng/mL who are not suspected of having prostate cancer by whatever means should undergo %fPSA measurement and be carefully monitored at short intervals over the long-term if they have lower %fPSA levels.

Natural history of PSA increase with and without prostate cancer.

OBJECTIVES: To investigate the natural history of prostate-specific antigen (PSA) increase in men with and without prostate cancer to clarify the probability of cancer-related PSA increase. METHODS: Between 1986 and 2001, 504 men aged 79 years or younger with baseline PSA levels of 4.0 ng/mL or less and a PSA increase greater than 4.0 ng/mL on consecutive screening were enrolled in this study. The types of PSA increase were classified as "non-cancer-related PSA increase," "suspicious cancer-related PSA increase," and "cancer-related PSA increase." The probability of a "cancer-related PSA increase" was investigated and stratified by baseline PSA levels and elapsed years until the PSA level increased to greater than 4.0 ng/mL. RESULTS: The probability of a "non-cancer-related increase," "suspicious cancer-related PSA increase," and "cancer-related PSA increase" was 57%, 15%, and 28%, respectively. The PSA velocity before the PSA increase was not significantly different between those with and without prostate cancer. A "non-cancer-related PSA increase" was observed in 92% of those with a PSA increase within 2 years of baseline PSA ranges of 2.0 ng/mL or less. Regardless of elapsed years until a PSA increase to greater than 4.0 ng/mL, a "suspicious cancer-related PSA increase" or "cancer-related PSA increase" was observed in almost one half of those with baseline PSA levels of 2.1 to 4.0 ng/mL. CONCLUSIONS: Intensive serial observations should be recommended before undergoing biopsy for those with a PSA increase within 2 years of a baseline PSA range of 0.0 to 2.0 ng/mL. It may be difficult to distinguish between those with and without cancer using only subsequent total PSA measurements for the remaining cases, and prostate biopsy should be recommended at present.