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1.
Br J Cancer ; 94(6): 820-7, 2006 Mar 27.
Article in English | MEDLINE | ID: mdl-16508636

ABSTRACT

The purpose of this study was to explore the incidence of late relapse in patients with malignant germ cell tumour (MGCT) in a population-based series, with emphasis on the mode of detection, survival, and the relevance of histological findings. The clinical records from a population-based cohort of patients with seminoma (n=1123) or non-seminoma (n=826) were evaluated for late relapses. Twenty-five patients developed a late relapse. The cumulative 10-year incidence rate was 1.3%. All 10 seminoma patients, but only eight of 15 non-seminoma patients relapsed with vital malignant tumour (P=0.02). Teratoma or necrosis was found in seven of nine primarily chemotherapy-treated non-seminoma patients with normal tumour markers at late relapse. Six of nine patients operated with limited retroperitoneal lymph node dissection as part of the primary treatment had relapsed retroperitoneally outside the original operation field. The 10-year cause-specific survival was 68% in all patients, 50% in patients relapsing with vital malignant tumour and 100% in those with teratoma/ necrosis before or after salvage chemotherapy. The 10-year incidence rate of late relapses of 1.3% might reflect the true incidence rate in a population-based cohort of MGCT patients, with cure in at least half of them.


Subject(s)
Neoplasm Recurrence, Local/epidemiology , Neoplasms, Germ Cell and Embryonal/pathology , Seminoma/pathology , Testicular Neoplasms/pathology , Adult , Aged , Cohort Studies , Humans , Incidence , Male , Middle Aged , Necrosis , Neoplasm Recurrence, Local/diagnosis , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/surgery , Seminoma/drug therapy , Seminoma/surgery , Testicular Neoplasms/drug therapy , Testicular Neoplasms/surgery , Time Factors
2.
Br J Cancer ; 93(7): 749-56, 2005 Oct 03.
Article in English | MEDLINE | ID: mdl-16136047

ABSTRACT

Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 x 10(7) transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre- and postvaccination peripheral blood samples. Serum prostate-specific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n = 19, P = 0.002, r = 0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients.


Subject(s)
Androgens/therapeutic use , Cell Transplantation , Dendritic Cells/immunology , Immunotherapy , Prostatic Neoplasms/therapy , RNA, Messenger/genetics , Transfection , Aged , Cancer Vaccines/adverse effects , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Drug Resistance, Neoplasm , Humans , Hypersensitivity, Delayed , Male , Middle Aged , Prostate-Specific Antigen/blood
3.
Eur J Surg Oncol ; 29(5): 455-8, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12798751

ABSTRACT

AIM: Three papers including five patients have described en bloc radical prostatectomy for locally advanced rectal cancer. METHODS: Six patients (median age 63 years) underwent en bloc radical prostatectomy for locally advanced (3) or recurrent (3) rectal cancer involving the prostate. Quality of life questionnaires were answered postoperatively and the data prospectively entered in a database. RESULTS: One primary case had low anterior resection (LAR), the others abdominoperineal resections (APR) of R0 stage. Two recurrent cases had APRs and one tumour resection-all R1 stage. Anastomotic leakage led to construction of an ileal conduit in one patient and in two healed on conservative treatment. Follow up was 10-50 months. One patient died from distant metastases at 29 months postoperatively, one was operated for a single lung metastasis and one has disseminated lung metastases. None has developed local recurrence. Four of the five with anastomoses had good quality of life and none wanted an ileal conduit. CONCLUSION: In spite of a relatively high urinary leak rate the total complication rate seems to be lower than after pelvic exenteration. En bloc radical prostatectomy seems an option in selected patients otherwise needing pelvic exenteration for locally advanced or recurrent rectal cancer.


Subject(s)
Prostatectomy , Prostatic Neoplasms/surgery , Rectal Neoplasms/surgery , Aged , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Postoperative Complications/epidemiology , Prostatic Neoplasms/pathology , Quality of Life , Rectal Neoplasms/pathology , Treatment Outcome
4.
Eur J Surg Oncol ; 27(7): 645-51, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11669593

ABSTRACT

AIMS: When locally advanced or recurrent rectal cancer involves the bladder or prostate, curative treatment often requires pelvic exenteration. The aim was to assess the quality of life (QoL) in disease-free patients with urinary diversion after extensive surgery for advanced rectal cancer. METHODS: Twelve patients with urinary diversion (cases) were compared with 25 randomly selected patients given the same treatment, but without urinary diversion (controls). An age- and gender-adjusted general population was identified (reference). QoL was assessed with the EORTC questionnaires QLQ-C30, QLQ-CR38, and parts of the QLQ-BLM30. RESULTS: The cases did not report significantly worse overall QoL than the controls or the reference population. Both cases and controls had low mean scores of sexual function, and high mean scores of male sexual problems. In the nine cases that had two stomas, overall QoL was not worse than in the control or reference groups. CONCLUSIONS: Tumour-free patients did not report worse QoL scores than the controls or the general population, despite most having two stomas and low sexual function. Fear of reducing the patient's QoL should not be a major contraindication when surgery with urinary diversion is warranted to obtain curative resection.


Subject(s)
Cystostomy , Quality of Life , Rectal Neoplasms/surgery , Aged , Aged, 80 and over , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Norway , Postoperative Complications , Statistics, Nonparametric
5.
Genes Chromosomes Cancer ; 28(2): 211-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10825006

ABSTRACT

Cancer of the prostate remains poorly characterized cytogenetically. This is due in part to methodological problems and in part to the paucity of radical prostatectomies, until now the main source of material for cytogenetic analyses. We have improved existing techniques for the culturing of prostatic neoplasms removed by radical prostatectomy or sampled by ultrasound-guided needle biopsy. Successful short-term cultures were obtained from all 10 prostatectomy samples and from all 10 ultrasound-guided needle biopsies, always with a pure epithelial morphology. Of the 19 cases yielding a sufficient number of high-quality metaphases for chromosome banding analysis, the single atypical epithelial hyperplasia had a normal karyotype, whereas both prostatic intraepithelial neoplasias and 12 of 16 (75%) invasive carcinomas were shown to have clonal abnormalities. Ten of the 12 (83%) karyotypically abnormal invasive carcinomas presented structural chromosomal rearrangements. A recurrent deletion, del(10)(p13), was seen in three tumors; in one of them the terminal nature of the deletion was confirmed by two-color FISH. A del(17)(p11) was seen in one PIN lesion, but since the analysis of exons 4-8 of the TP53 tumor suppressor gene revealed no mutations, there probably was no inactivation of the second TP53 allele. Our study thus leads to the following main conclusions. First, better culturing methods allow the detection of abnormal karyotypes in a much higher percentage of prostatic neoplasms than has hitherto been possible. Second, ultrasound-guided needle biopsies of prostatic neoplasms are a sufficient source of material for cytogenetic analysis. Third, a terminal deletion of the short arm of chromosome 10, del(10)(p13), seems to identify a subgroup of prostatic cancer.


Subject(s)
Chromosome Aberrations/diagnostic imaging , Chromosome Aberrations/genetics , Prostatectomy/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/genetics , Biopsy, Needle , Chromosome Aberrations/pathology , Chromosome Disorders , Clone Cells , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Male , Prostatic Neoplasms/pathology , Ultrasonography
6.
BJU Int ; 85(3): 270-5, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10671880

ABSTRACT

OBJECTIVE: To detect occult regional lymph node metastases in patients with T3pN0M0 prostate cancer not recognized by routine haematoxylin and eosin staining, and to evaluate the clinical relevance of this finding. PATIENTS AND METHODS: Formalin-fixed and paraffin-embedded pelvic lymph nodes (1118) from 92 patients were evaluated by immunohistochemistry using antibodies for prostate specific antigen (PSA) and pancytokeratin (AE1/AE3). Of the tumours, 14% were well, 69% moderately and 17% poorly differentiated. The extent of tumour was categorized as T3pN0M0 in all patients, who were referred for definitive radiotherapy after pelvic staging lymphadenectomy. The median (range) serum PSA value before treatment was 18.5 (0.4-342) microg/L. After radiotherapy, the patients were followed by assessing biochemical progression, pelvic recurrence and/or development of distant metastases. The median (range) observation time for all patients was 61 (16-136) months. RESULTS: Occult lymph node metastases were detected in four (4.4%) of the 92 patients. Patients with or without occult metastases had similar serum PSA levels and histological grades. None of the four patients with occult metastases progressed, compared with 37 of the 88 (42%) with no such metastases. CONCLUSION: Using immunohistochemistry the detection rate of occult lymph node metastases in patients with T3pN0M0 prostate cancer is low. The occurrence of such metastases is probably unrelated to the serum PSA value before treatment. The short-term outcome of patients subsequently treated with definitive radiotherapy does not seem to be associated with the finding of occult lymph node metastases, but long-term follow-up is needed. So far, the results do not justify the search for occult lymph node metastases as a routine procedure in these patients


Subject(s)
Prostatic Neoplasms/radiotherapy , Aged , Humans , Immunohistochemistry/methods , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Middle Aged , Pelvis , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/immunology , Prostatic Neoplasms/pathology
7.
Br J Cancer ; 80(1-2): 249-55, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10390004

ABSTRACT

The purpose of this study was to evaluate fertility after different types of post-chemotherapy retroperitoneal lymph node dissection (RPLND). During 1980-1994, 192 patients with metastatic testicular cancer underwent post-chemotherapy RPLND with a gradual shift from modified bilateral template RPLND to nerve-sparing RPLND. Modified bilateral template RPLND was done in 92% of the patients operated during 1980-1984 as compared to 16% during 1989-1994. Pre- and post-treatment fertility was assessed by microscopic sperm analysis, determination of serum FSH and information on ejaculation and paternity. There was no significant difference of the survival rates between the three treatment periods. Antegrade ejaculation was preserved in 11% of the patients after modified bilateral template RPLND as compared to 89% after the nerve-sparing operation technique. The median ejaculatory volume decreased post-operatively, serum FSH increased and sperm density remained unchanged. Fifty-six patients attempted fatherhood after their treatment, and 27 fathered at least one child after an observation-time of 55 months, nine of them by assisted fertilization. Patients with initially advanced testicular cancer but limited residual retroperitoneal masses after induction chemotherapy can safely undergo limited post-chemotherapy RPLND as a part of multimodality treatment. After nerve-sparing RPLND antegrade ejaculation is preserved in 89% of the patients though the ejaculatory volume decreases after RPLND. Post-treatment fatherhood can be achieved in at least 50% of the patients attempting paternity.


Subject(s)
Ejaculation , Testicular Neoplasms , Adolescent , Adult , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Humans , Lymph Node Excision , Male , Middle Aged , Neoplasm Metastasis , Orchiectomy , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Treatment Outcome
8.
Int J Radiat Oncol Biol Phys ; 43(4): 735-43, 1999 Mar 01.
Article in English | MEDLINE | ID: mdl-10098428

ABSTRACT

PURPOSE: To assess morbidity, side effects, and quality of life (QoL) in patients treated for localized prostate cancer with curative aim. METHODS AND MATERIALS: This descriptive cross-sectional study comprises 154 patients who had undergone definitive radiotherapy (RAD) and 108 patients with radical prostatectomy (PRECT) at the Norwegian Radium Hospital during 1987-1995. At least 1 year after treatment the patients completed several questionnaires assessing quality of life (European Organization for Research and Treatment of Cancer QLQ-C30 instrument [EORTC QLQ-C30]), lower urinary tract symptoms (LUTS): International Prostate Symptom Score (IPSS), or sexuality (selected questions from the Psychosocial Adjustment to Illness Scale [PAIS]). Urinary incontinence and bowel distress were evaluated by ad hoc constructed questionnaires. A control group (OBS) consisted of 38 patients following the watch-and-wait policy. RESULTS: Twenty percent of the patients from the RAD Group had moderate (14%) or severe (6%) LUTS as compared to 12% in the PRECT group. However, 35% of men from the latter group reported moderate to severe urinary incontinence. "Overall" sexuality was moderately or severely impaired in 71% of the PRECT and 50% of the RAD patients. In the former group high age was correlated with erectile impotency (p < 0.001). In the RAD comorbidity was associated with erectile impotency (p < 0.001). Between 13-38% of the patients recorded moderate or severe bowel distress (blood per rectum: 13%; bowel cramps: 26%; flatulence: 38%), without significant differences comparing patients who had received conventional small 4-field box radiotherapy and patients who had undergone strictly conformal radiotherapy. Despite malignancy and/or treatment-related morbidity, QoL was comparable in both groups with respectively 9% and 6% RAD and PRECT patients, reporting moderately or severely impaired QoL. In the multivariate analysis physical function, emotional function and fatigue were significantly correlated with QoL, whereas sexuality, lower urinary symptoms, and urinary incontinence correlated with QoL only in the univariate analysis. CONCLUSION: In spite of considerable malignancy and/or treatment-related morbidity QoL was good or only slightly impaired in the majority of patients with localized prostate cancer who presented with stable disease > 1 year after definitive radiotherapy or radical prostatectomy with no difference as compared to the age-matched normal population. Clinicians should be aware of the fact that general QoL dimensions (physical function, emotional function, fatigue) are as a rule of greater significance for QoL than sexuality and lower urinary tract symptoms.


Subject(s)
Prostatectomy , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Quality of Life , Sexual Dysfunction, Physiological/etiology , Urinary Incontinence/etiology , Aged , Aged, 80 and over , Analysis of Variance , Cross-Sectional Studies , Erectile Dysfunction/etiology , Follow-Up Studies , Gastrointestinal Diseases/etiology , Humans , Male , Middle Aged , Neoplasm Staging , Prostatic Neoplasms/pathology , Radiotherapy, Conformal/adverse effects , Surveys and Questionnaires
9.
Acta Oncol ; 35 Suppl 8: 59-65, 1996.
Article in English | MEDLINE | ID: mdl-9073049

ABSTRACT

This retrospective study includes 534 patients who had curatively intended treatment for T2/T3/T4a bladder cancer at the Norwegian Radium Hospital during the period 1980-1990. Total cystectomy preceded by preoperative radiotherapy represented the treatment of choice in 263 patients (CysGr). High-dose radiotherapy was applied in 271 patients in whom total cystectomy could not be performed (RadGr). From 1985 neo-adjuvant cisplatin-based chemotherapy was increasingly used. The 5-year crude survival rate for all patients was 35% with 40% for CysGr and 22% for RadGr. In CysGr the 5-year survival rate was highest (63%) for patients with

Subject(s)
Urinary Bladder Neoplasms/mortality , Adult , Aged , Chemotherapy, Adjuvant , Cisplatin/therapeutic use , Combined Modality Therapy , Cystectomy , Female , Humans , Male , Middle Aged , Prognosis , Radiotherapy Dosage , Retrospective Studies , Survival Analysis , Urinary Bladder Neoplasms/radiotherapy , Urinary Bladder Neoplasms/surgery
10.
J Urol ; 154(6): 2118-22, 1995 Dec.
Article in English | MEDLINE | ID: mdl-7500472

ABSTRACT

PURPOSE: We attempt to contribute to the understanding of the natural history of prostate cancer metastatic to lymph nodes. MATERIALS AND METHODS: A total of 61 patients with node-positive prostate cancer was prospectively followed without adjuvant treatment for an average of 41 months. The impact of T and P categories, grade, tumor volume and prostate specific antigen change on interval to progression was studied in a univariate and multivariate analysis. RESULTS: Median interval to progression was 18 months, and correlated with grade and prostate specific antigen doubling time. Changes in prostatic volume with time were not predictive. CONCLUSIONS: Our study provides insight into the natural history of node-positive disease and identifies relevant prognostic factors that may be used for treatment decisions.


Subject(s)
Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prospective Studies , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood
11.
Br J Urol ; 75(4): 502-6, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7540482

ABSTRACT

OBJECTIVE: To analyse the increase of serum prostatic specific antigen (PSA) as a means of early detection of progression in hormonally untreated or androgen-deprived patients with T1-T4, pN+ and MO prostate cancer. PATIENTS AND METHODS: From 1986 to 1992 40 patients with T1-T4 pN+ MO prostate cancer were either deprived of androgen at diagnosis (Group 1, 19 patients) or had no immediate hormone manipulation (Group 2, 21 patients) and were followed at 3-6-monthly intervals when determinations of PSA and routine clinical/radiological examinations were performed. A significant increase in PSA was defined as a > or = 50% increase of the baseline PSA value which was the either the lowest PSA value within 6 months from the start of androgen deprivation (Group 1) or the initial PSA value (Group 2). RESULTS: By June 1993 22 of the 40 patients had clinically progressed. In 12 patients the progression was preceded by a significant increase in PSA (Group 1, three of four progressing patients; Group 2, nine of 18 progressing patients). A PSA increase of > or = 50% was observed simultaneously with clinical progression in six patients, whereas clinical progression occurred in four patients with no previous or simultaneous significant increase in PSA. In four of nine hormonally untreated patients > or = 1 year elapsed between antecedent PSA increase and clinical progression. CONCLUSION: In routine clinical practice PSA does not significantly increase (> or = 50% of baseline value and > 10 micrograms/L) before disease progression in about one third of patients with pN+ MO prostate cancer managed with or with no hormone manipulation. Future studies should be carried out to determine whether a lower rate of increase in PSA during follow-up has any clinical significance.


Subject(s)
Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Aged , Disease Progression , Follow-Up Studies , Hormones/therapeutic use , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Prospective Studies , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy
12.
Br J Urol ; 73(5): 554-60, 1994 May.
Article in English | MEDLINE | ID: mdl-8012779

ABSTRACT

OBJECTIVE: To evaluate sexuality after successful treatment of penile cancer. PATIENTS AND METHODS: Post-therapy sexuality was evaluated in 30 men (median age 57 years; range 28-75) treated for cancer of the penis 80 months previously (median; range: 11-225 months). Treatment regimes were: local excision/laser beam treatment, 5; definitive radio-therapy, 12; partial penectomy, 9; total penectomy, 4. Patients underwent a semi-structured interview and completed three self-administered questionnaires (psychosocial adjustment to severe illness [PAIS], mental symptoms [GHQ], quality of life [EORTC QLQ C-30]). A global score of overall sexual functioning was constructed consisting of sexual interest, sexual ability, sexual satisfaction, sexual identity, partner relationship and frequency of coitus. RESULTS: In 10 of 12 patients treated by irradiation the sexual global score was not or only slightly reduced compared with two of nine patients after partial penectomy and one of five patients with local surgery/laser beam treatment. All four patients who had undergone total penectomy recorded a severely reduced sexual global score. Of the six single domains, sexual identity and partner relationship did not change with increasing age, whereas the other scores of sexual life deteriorated as the patient became older. In the patients treated by irradiation doctors evaluated the patients' post-treatment sexuality to be more impaired than that experienced by the patients. CONCLUSION: Within the limitations due to the small number of patients studied, radiotherapy seems to be the treatment of choice in limited cancer of the penis if preservation of sexuality is a major therapeutic aim. Physicians counselling patients with this rare malignancy need more information about treatment-related problems of sexuality after different therapeutic modalities.


Subject(s)
Penile Neoplasms/psychology , Sex , Sexual Dysfunction, Physiological/etiology , Adult , Age Factors , Aged , Attitude of Health Personnel , Attitude to Health , Follow-Up Studies , Humans , Male , Middle Aged , Penile Neoplasms/radiotherapy , Penile Neoplasms/surgery , Penis/surgery , Postoperative Complications
13.
Cancer ; 72(10): 3036-43, 1993 Nov 15.
Article in English | MEDLINE | ID: mdl-8221571

ABSTRACT

BACKGROUND: The role of radiation therapy as curative treatment of muscle-invasive bladder cancer was to be analyzed. METHODS: From 1980-1990, 308 patients with transitional cell carcinoma of the urinary bladder received definitive pelvic radiation therapy (nominal standardized dose greater than or equal to 1700 ret). T categorization was based on clinical examination assessing the palpability of the bladder tumor and its extent (TNM 1978/1982). RESULTS: The cancer-specific 5-year survival rate for all patients was 24% (crude survival, 20%). The 135 patients with T2/T3a tumors lived significantly longer (5-year survival, 38%) than those with greater than or equal to T3b tumors (5-year survival, 14%). In the former group of patients, age (75 years and younger versus older than 75 years) was significantly correlated with a favorable outcome. The cancer-specific 2-year survival was significantly correlated to clinical response assessed 3-4 months after radiation therapy was 72%, 38%, and 10% in cases of complete response, partial response, and no response/inevaluability, respectively. In a multivariate analysis, the T categorization, patient age, serum creatinine level (less than or equal to 150 mumol/l versus greater than 150 mumol/l), and radiation therapy schedule predicted the 5-year survival rate. CONCLUSIONS: The clinical T category (< or = T3a versus > or = T3b), based on bimanual palpation, represents an important prognostic parameter, if done by clinicians experienced in onco-urology. High-dose radiation therapy offers a reasonable chance for long-term survival in patients with T2/T3 tumors confined to the bladder wall, especially in patients younger than 76 years. Greater than or equal to 80% of patients with more extended tumors (greater than or equal to T3b) and those older than 75 years of age are not curable by radiation therapy alone. In these patients palliative treatment modalities should be considered, in particular if cisplatin-based chemotherapy is not feasible.


Subject(s)
Carcinoma, Transitional Cell/radiotherapy , Muscle, Smooth/pathology , Urinary Bladder Neoplasms/radiotherapy , Adult , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Prognosis , Radiotherapy Dosage , Regression Analysis , Remission Induction , Retrospective Studies , Survival Rate , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
14.
Cancer ; 72(10): 3044-51, 1993 Nov 15.
Article in English | MEDLINE | ID: mdl-8221572

ABSTRACT

BACKGROUND: The role of total cystectomy was to be assessed in the curative treatment of muscle-invasive bladder cancer. METHODS: Two hundred and fifty-three patients with T2-T4a transitional cell carcinoma of the urinary bladder were referred to precystectomy radiation therapy (46 Gy, 66 patients; 20 Gy, 187 patients). These patients represented approximately 20% of all patients developing muscle-invasive bladder cancer in Southern Norway from 1980-1990. The clinical T categorization was generally based on palpability and extent of the palpable bladder tumor assessed by the referring urologist. Twenty-six patients (10%) did not have total cystectomy, most often due to peroperatively demonstrated locoregional inoperability. Two or three cycles of cisplatin-based combination chemotherapy were given to 68 patients. RESULTS: For the 227 patients who underwent cystectomy, the cancer-specific 5-year survival rate was 58% (T2 [104 patients], 63%; greater than or equal to T3 [123 patients], 54%) (P = 0.022). The comparable figure for patients with histologically proven regional lymph node metastases was 22%. The 97 stage-reduced cases (less than or equal to pT1) survived significantly longer than the 130 patients without stage reduction (74% versus 46%) (P < 0.0001). Neoadjuvant chemotherapy was correlated with a more favorable survival in patients with greater than or equal to T3 tumors but did not seem to influence survival of patients with T2 bladder cancer. CONCLUSIONS: In a multicenter setting, prognostically relevant T categorization of operable muscle-infiltrating bladder cancer can be based on the palpability of the primary tumor. Approximately 50% of favorably selected patients with operable T2-T4 bladder cancer survived for at least 5 years independent of whether the operation was done at a large uro-oncologic unit or a smaller urologic section. In this retrospective review, chemotherapy seemed to improve the survival in patients with deeply infiltrating (greater than or equal to T3) bladder cancer but appeared to represent an overtreatment in patients with T2 tumors.


Subject(s)
Carcinoma, Transitional Cell/surgery , Cystectomy , Muscle, Smooth/pathology , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Analysis of Variance , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Norway , Regression Analysis , Retrospective Studies , Survival Rate , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
15.
Br J Cancer ; 68(3): 572-8, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8102536

ABSTRACT

DNA ploidy and S-phase fraction (SPF), determined by flow cytometry were studied in 118 patients with muscle-invasive transitional cell carcinoma (TCC) of the urinary bladder, scheduled for cystectomy after pre-operative radiotherapy (20 Gy/1 week) with or without systemic cisplatin-based neo-adjuvant chemotherapy. The correlation between these parameters and immunohistochemically demonstrated p53, c-erbB-2 and HCG was also investigated. There were 16 DNA diploid and 102 DNA non-diploid tumours. DNA ploidy was not related to the T (all 118 patients) or pN (58 patients) category, occurrence of stage reduction or cancer-related 5 years survival. Patients with high SPF tumours tended, however, to have a better prognosis than those with low SPF TCC reaching the level of significance (P < 0.05) for those patients who had high SPF tumours and received neo-adjuvant chemotherapy. Fifty-one of the tumours were p53 positive. p53 positive tumours were significantly more often found in TCC with low SPFs than in those with high SPFs. Respectively 12 and 9% of the tumours were HCG and c-erbB-2 positive, without correlation to DNA ploidy or SPF. We conclude that DNA ploidy does not represent a prognostic parameter in muscle-invasive operable bladder carcinomas. A high SPF, determined by FCM, may be helpful to identify patients with chemotherapy-sensitive TCC of the urinary bladder.


Subject(s)
Chorionic Gonadotropin/metabolism , Oncogene Proteins, Viral/metabolism , Ploidies , S Phase , Tumor Suppressor Protein p53/metabolism , Urinary Bladder Neoplasms/genetics , Adult , Female , Flow Cytometry , Humans , Immunohistochemistry , Male , Middle Aged , Receptor, ErbB-2 , Urinary Bladder Neoplasms/radiotherapy
16.
Br J Cancer ; 68(2): 380-4, 1993 Aug.
Article in English | MEDLINE | ID: mdl-7688548

ABSTRACT

Pre- and post-treatment specimens from 47 patients with hormone resistant prostatic carcinoma were compared with each other regarding histological grade and immunoreactivity for p53 protein, neuron specific enolase and c-erbB-2 protein. Significantly more specimens expressed a high malignancy grade when the tumour had become hormone resistant than at the time of initial diagnosis (Gleason P: < 0.0001, WHO P:0.0003). p53 protein immunoreactivity increased significantly with disease progression (P:0.006), while tissue PSA immunoreactivity was reduced in post-treatment specimens (P:0.011). p53 protein expression did not correlate with histological grade or PSA expression and seems to be an independent parameter which participates late in the neoplastic transformation. Thirty-two percent of the tumours were neuron specific enolase positive, but this parameter did not correlate with development of hormone resistance. c-erbB-2 protein reactivity was not recognised.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Adenocarcinoma/blood , Adenocarcinoma/surgery , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/blood , Drug Resistance , Estrogens/therapeutic use , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Immunohistochemistry , Male , Middle Aged , Orchiectomy , Palliative Care , Prognosis , Prostate-Specific Antigen/analysis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Proto-Oncogene Proteins/analysis , Receptor, ErbB-2 , Tumor Suppressor Protein p53/analysis
17.
J Urol ; 148(3): 838-41; discussion 841-2, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1512835

ABSTRACT

Deoxyribonucleic acid (DNA) flow cytometry and light microscopy were performed in pre-radiotherapy and post-radiotherapy biopsies obtained from the primary tumor in 31 patients with prostate cancer. Radiotherapy was applied by means of transperineal 125iodine (125I) implantation. Of the patients 21 had pretreatment biopsies and in 19 of these biopsies also were performed 1 and/or 1 1/2 years after the 125I implantation. Posttreatment biopsies were available for DNA flow cytometry in 12 additional patients without pretreatment DNA flow cytometry assessment. Of the 21 pretreatment biopsies 7 were diploid, 6 tetraploid and 8 aneuploid. All 31 posttreatment biopsies were either tetraploid (21) or aneuploid (10). All 6 pretreatment diploid tumors became tetraploid after radiotherapy. At 1 and/or 1 1/2 years after 125I implantation residual tumors were found in 28 of 31 prostatic glands. The high frequency of nondiploid DNA stemlines 1 or more years after 125I implantation and the high rate of residual tumor leave some doubt about the radiocurability of prostate cancer by the chosen radiotherapy technique.


Subject(s)
Brachytherapy , DNA, Neoplasm/analysis , Iodine Radioisotopes/therapeutic use , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Biopsy , Flow Cytometry , Humans , Male , Ploidies , Prospective Studies , Prostatic Neoplasms/genetics , Time Factors
18.
Br J Cancer ; 66(1): 181-4, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1379059

ABSTRACT

Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate cancer had normal serum levels of prostate specific antigen (PSA less than or equal to 10 micrograms l-1), when referred for secondary treatment. PSA was significantly correlated with the extent of skeletal metastases (R: 0.35) and the levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a multivariate Cox regression analysis the survival of the 152 patients was not correlated with the PSA level but with the patients performance status, the level of hemoglobin, and the time between primary hormone treatment and relapse. The lack of serum PSA to predict survival may be explained by a heterogenous composition of hormone resistant prostate cancer as regards differentiated and/or PSA producing vs undifferentiated and/or PSA non-producing cells.


Subject(s)
Antigens, Neoplasm/analysis , Biomarkers, Tumor/blood , Prostatic Neoplasms/blood , Aged , Alkaline Phosphatase/blood , Androgens/physiology , Bone Neoplasms/blood , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Creatinine/blood , Drug Resistance , Follow-Up Studies , Humans , Male , Neoplasm Metastasis , Prognosis , Prostate-Specific Antigen , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Reference Values , Time Factors
19.
Cytometry ; 13(4): 395-403, 1992.
Article in English | MEDLINE | ID: mdl-1526198

ABSTRACT

In 49 pairs of contiguous sections from paraffin-embedded prostatic cancer tissue, the DNA indices (DIs) were determined by flow cytometry (FCM) at 2 different laboratories. In 3 of 45 pairs of evaluable nuclear suspensions, DIs of 1.1 (DNA aneuploid) were found at Laboratory 1, whereas all 3 tumours were classified as DNA diploid at Laboratory 2. In the remaining 42 specimens, the correlation between the DIs was excellent, though the application of strictly defined DNA ploidy ranges led to different DNA ploidy allocation in 3 cases. It is concluded that in 85-90% of the cases, reliable DIs can be obtained by FCM done in paraffin-embedded material at different laboratories. Slight technical variations and interpretation differences may lead to different ploidy allocation in 10-15% of the cases.


Subject(s)
DNA, Neoplasm/analysis , Ploidies , Prostatic Neoplasms/pathology , Aneuploidy , Cell Nucleus/chemistry , Flow Cytometry , Humans , Laboratories, Hospital , Lymphatic Metastasis/pathology , Male , Paraffin , Prostatic Neoplasms/chemistry , Reproducibility of Results
20.
Eur Urol ; 22(1): 33-8, 1992.
Article in English | MEDLINE | ID: mdl-1385143

ABSTRACT

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in the serum of 69 patients with clinical T3/T4M0 prostatic cancer before staging lymphadenectomy. In principle, high-dose radiotherapy was given only to patients of pathological N0 category. Seventeen patients had a prelymphadenectomy PSA level below the normal upper reference limit (10 micrograms/l) and only 3 of them had pelvic lymph node metastases. Fifteen of 52 patients with a preoperative PSA level > or = 10 micrograms/l were of N0 category. Only 8 of the 41 evaluable patients had PAP values above the normal range, and 6 of these 8 patients had pelvic lymph node metastases. Preoperative PSA values, but not preoperative PAP levels, assist the clinician in predicting regional lymph node metastases in patients with clinical T3/T4M0 prostatic cancer. Two-thirds of the patients with T3/T4 tumours and PSA values between 10 and 50 micrograms/l have regional lymph node metastases. About 80% of the patients with PSA levels < 10 micrograms/l belong to the N0 category. About 75% of the patients with PSA > 50 micrograms/l have N+ disease. Taking into account the individual preoperative PSA values, the indication for preradiotherapy staging lymphadenectomy should be balanced between the chance of demonstrating N+ disease, the expected postoperative morbidity and the benefit for the patient found to be of N0 category.


Subject(s)
Acid Phosphatase/blood , Lymphatic Metastasis/diagnosis , Prostate-Specific Antigen/blood , Prostate/enzymology , Prostatic Neoplasms/pathology , Aged , Biomarkers, Tumor/blood , Humans , Lymph Node Excision , Male , Middle Aged , Neoplasm Staging , Pelvis , Predictive Value of Tests , Prostatic Neoplasms/diagnosis , Sensitivity and Specificity
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