Early diagnosis and surgical management of prostate cancer

Prostate cancer is a significant cause of morbidity and mortality in the United States and Europe. The natural ageing of the population as well as the continued and widespread use of diagnostic tests such as prostate specific antigen (PSA), has led to an increase in the numbers of men diagnosed with localised prostate cancer. Screening to identify organ-confined disease has provoked much public and scientific attention, but remains controversial. Radical prostatectomy is one of the most challenging urological procedures performed. Improvements in technique due to better understanding of pelvic anatomy have reduced complications, with acceptable standards and excellent results in high-volume institutions. Continual refinements in technique and the recent introduction of laparoscopic radical prostatectomy are likely to improve functional outcome further. However the effectiveness of surgery in improving survival and quality of life, in men with early prostate cancer remains to be determined. The results from large randomised controlled trials are eagerly awaited.     

Stratégies thérapeutiques actuelles du cancer de la prostate hormonorésistant

Prostate cancer is the most common cancer diagnosed in American males, and is the second leading cause of cancer-related deaths. Most patients who develop metastatic disease will initially respond to androgen deprivation, but response is invariably temporary. Most patients will develop androgen-independent (“hormone-refractory”) disease that results in progressive clinical deterioration and ultimately death. This progression to androgen independence is accompanied by increasingly evident DNA instability and alterations in genes and gene expression, including mutations in p53, over-expression of Bcl2, and mutations in the androgen receptor gene, among others. Treatment options for hormone-refractory disease include intensive supportive care, radiotherapy, bisphosphonates, second-line hormonal manipulations, cytotoxic chemotherapy and investigational agents. A post-treatment reduction in the level of prostate specific antigen (PSA) by 50% has been shown to correlate with survival and has been accepted by consensus as a valid endpoint in clinical trials. Chemotherapeutic agents such as mitoxantrone, estramustine, and the taxanes have yielded improved response rates and palliative benefit, but not improved survival. Therefore, current efforts must be focused on enrolling patients onto clinical trials of investigational agents with novel mechanisms of action, and on using survival, time to progression, and quality of life as end points in routine clinical practice.     

Ganglion curage in prostate cancer

In clinically Localized prostate cancers, the interest of pelvic Lymphadenectomy is debated. Nevertheless, this intervention provides important information on disease prognosis (number of positive lymph nodes, tumoural volume, and extracapsular perforation of the affected ganglions); information that previously no other technique could provide. However, no consensus exists concerning patients who should benefit from pelvic Lymphadenectomy and on the extent of this intervention. For most surgeons, decision making regarding ganglion curage is based on nomograms. According to these nomograms, patients with a level of prostate specific antigen (PSA) <10 ng/mL and a Gleason score <7 have a very low risk for ganglionic metastases; this is the reason why the benefit of pelvic Lymphadenectomy remains controversial. Besides, most of these nomograms are based upon the results of standard Lymphadenectomy (iliac vein and obturator fossa) with, subsequently, a related risk of imprecision. In addition, potential therapeutic benefit may be expected from extended ganglion curage, despite the fact that this is not clearly documented yet, due to the benign course of the disease. In other tumoural diseases (stomach cancer, breast cancer, colorectal cancer, blade cancer), on the contrary, survival and stage identification depend on the number of removed ganglions, thus on the extent of Lymphadenectomy.     

Techniques, indications and results of permanent prostate brachytherapy for localized prostate cancer

Permanent seed brachytherapy as a monotherapy is an appropriate treatment in patients with low risk localized prostate cancer such as intraprostatic cancer, T1-2 stage, PSA less than 10 ng/mL, low tumour volume, well differentiated cancer (Gleason score less than 7), gland size less than 50 mL, no micturition symptoms that could decompensate after implantation. A brachytherapy program needs a specialized multidisciplinary team with the collaboration of urologists, radiotherapists (authorized person to manipulate radioactive elements), and physicists. The 10-year oncologic and morbidity results have been published in the literature and are comparable to those of other standard treatments of localized prostate cancer such as radical prostatectomy and external beam radiation therapy.     

Prostate cancer: Diagnosis and staging

The discovery and the use of serum prostate specific antigen (PSA) has considerably improved the diagnosis of prostate cancer during the past 20 years. Before PSA era, early diagnosis was only based on the digital rectal examination (DRE) of which the Limitations have been evidenced; over half of the tumours diagnosed by such means had already spread out of the prostate and were incurable. Assessment of serum PSA has allowed the diagnosis to be made at an earlier stage of the disease, curable by current treatments. Whichever the diagnostic tools, transrectal ultrasound (TRUS) prostatic biopsies remain necessary for diagnosis ascertainment, taking into account the low specificity of PSA assessment. The feasibility of a diagnosis at an early and curable stage of the disease has logically resulted in screening procedures aimed at reducing the high mortality related to prostate cancer. The numerous publications on prostate cancer screening provide precise information on the accuracy of available diagnostic means (PSA, DRE, TRUS, combined PSA and DRE), on the characteristics of screened tumours (stage and differentiation), and also on the population of men likely to benefit from the screening (age at beginning and end of the screening, frequency of PSA testing, identification of the men with ethnic and/or genetic predisposition). In those early diagnosed prostate cancers, the assessment of loco-regional cancer extension (extracapsular and/or, microscopic nodal involvement), remains unsatisfactory because no imaging technique (ultrasonography, CT scan, MRI,...) allows visualising the tumour itself or microscopic metastases. Nevertheless, the combination of multiple parameters such as DRE data, PSA level, biopsy data and tumour differentiation helps approaching with an increasing precision (nomograms) the true pathologic stage of the disease. Such advances allow distinguishing, among the very heterogeneous group of prostate cancers, tumours that differ from one to another in terms of disease stage, progression and prognosis, which is helpful for the determination of an adapted therapeutic strategy.     

Screening for prostate cancer: synthesis

Screening for prostate cancer (PCa) remains a matter of debate. Although the results of two ongoing randomised trials will be available in 2008, mass screening of PCa is already effective in the United States where PCa-related mortality has very significantly decreased. However, such screening is strongly suspected to induce "over-diagnosis". This results in the treatment of insignificant PCa, but in a significant complication rate. This situation finds an explanation in the low specificity of PSA, the screening tool for aggressive PCa. ALL of the debate is based on a misunderstanding between the pros and the cons of screening. On one hand, if diagnosis is considered a search for knowledge, then advocate an "over-diagnosis" would mean advocate an "over-knowledge", which is nonsense. On the other hand, if treatment is considered a search for action on the natural history of a disease, then advocate an "over-treatment" would mean advocate an "over-action", which is meaningful. The problem induced by screening is not to search for a disease, but what we do with it when we find it! Before recommending mass screening for PCa, we have to re-educate our patients in their understanding of the disease and re-educate ourselves in our treatment decision process. Waiting for a governmental decision about PCa screening policy, one should actually consider individual screening, which allows for personal education of patients.     

Indications, techniques and outcomes of high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer

High-intensity focused ultrasound (HIFU) is a minimally invasive alternative for patients with localized prostate cancer, not suitable for radical prostatectomy because of a life expectancy less than 10 years or because of major co-morbidities precluding surgery. HIFU can be performed in patients with LUTS (associated TURP) or with a previous history of BPH surgery. HIFU is repeatable after the initial procedure if a recurrent cancer is diagnosed on control biopsies. Furthermore, this therapy is a viable option for patients with a local relapse after external beam radiation therapy: oncologic efficacy is conversely related to the initial prostate cancer stage before radiation therapy.     

Screening for prostate cancer: arguments "in favour"

Prostate cancer is a problem of public health; the relevance of its mass screening remains to be demonstrated by the conclusions of ongoing randomized prospective studies of which the preliminary results are promising. Yet, non-randomised and/or retrospective studies report a benefit of screening-related mortality. On such basis, French scientific authorities currently recommend individual screening.     

Biological markers of prostate cancer

Screening for prostate cancer is currently based on the assessment of blood prostate specific antigen (PSA). Although PSA was shown to be an adequate tool in prostate cancer screening, beginning from 4.0 ng/mL, its specificity is less significant. In men with a PSA between 4.0 and 10 ng/mL its predictive value is low. Therefore, there is a need for new instruments likely to improve the specificity of blood PSA levels between 4.0 and 10 ng/mL and the screening for prostate cancer in subjects with low PSA. Recent data are reviewed.     

Radiotherapy and chemotherapy in the treatment of oesophageal carcinoma

Surgery, chemotherapy and radiotherapy are the three major arms of treatment for cancer of the oesophagus, and combined modality therapy is required to treat advanced disease. Exclusive chemoradiotherapy is a feasible option for locoregionally advanced disease in responder patients. Elective surgery as a palliative procedure should not be regarded as a standard option in patients with metastatic or non-resectable oesophageal cancer. Surgery appears more and more as an adjuvant therapy in the curative treatment of oesophageal cancer, especially for advanced tumours.     

Active follow-up of prostate cancers

Today, earlier diagnosis of prostate cancer has allowed including, beside standard curative treatments, active follow-up of the disease. Such therapeutic management is based on a better knowledge of the natural history of prostate cancer and on possible detection of cases with slow progression. However, all criteria of selection of tumours that are likely to benefit from such surveillance are not always reliable and in some cases invasive treatment should replace surveillance. Analysis of active follow-up series shows that patients who benefit from such treatment have an unchanged prognosis. Active surveillance of prostate cancers may be considered a valuable option provided very strict limits are established regarding patients selection and follow-up.     

Results of surgical resection of squamous cells carcinoma of the oesophagus with or without preoperative radiochemotherapy: comparative and retrospective study

AIM OF THE STUDY: The aim of the study was to assess preoperative radio-chemotherapy for squamous cell carcinoma of the esophagus. MATERIAL AND METHODS: This study was a retrospective comparison between radio-chemotherapy followed by surgical resection (RCPO) and surgery alone. The RCPO group included patients with tumor located in the middle or lower third of the esophagus, staged T2 or T3 tumors without distant metastases by pretherapeutic assessment. These patients were matched with patients who underwent immediate surgery, who constituted the surgical group (CHIR). Both groups were matched for gender, age, tumor localization (middle or lower third), T stage, and surgical procedure. Each group included 77 men and 9 women, 50 tumors of the middle third and 36 of the lower third of the oesophagus, and 19 tumors T2 and 67 T3 ones. RESULTS: Morbidity of both groups was not significantly different. The mortality was 4% in the group CHIR and 12% in the group RCPO (P =0.07). The rate of radical resection (R0) was significantly higher in the RCPO group (74% vs. 51%; P =0.001). The overall 5-year survival rate was 38% after R0 surgery and 11% after R1 or R2 surgery (P <0.0001). After R0 surgery, the 5-year survival rate was 47% in the CHIR group and 32% in the RCPO group (P =0.06). CONCLUSION: Preoperative radiochemotherapy increases the rate of radical surgical resection without significant increase in postoperative morbidity and mortality.     

Hormone-refractory prostate cancer responding to capecitabine

A 66-year-old male patient with advanced prostate cancer presented with bony metastases, including pathologic fractures and hepatosplenomegaly. The patient responded to luteinizing hormone-releasing hormone agonists for more than 1 year. A clear progression while taking luteinizing hormone-releasing hormone agonists manifested as a progressive rise in prostate-specific antigen, alkaline phosphatase, hepatosplenomegaly, and myelophthisic pancytopenia. We administered capecitabine for 5 months with a complete clinical response. At last follow-up, the patient's liver function tests and prostate-specific antigen level have normalized. Liver size by computed tomography and blood counts both improved. To our knowledge, no previous case reports of capecitabine in the treatment of prostate cancer have been published.     

Vesico-urethral anastomosis during total laparoscopic prostatectomy

Vesico-urethral anastomosis is the last step of radical prostatectomy. Whatever the approach, radical prostatectomy remains a difficult surgical intervention. The dissection steps are similar whatever the selected access, open or laparostopic. Laparoscopic anastomosis requires specific skills that must be adequately mastered by the surgeon before starting any laparoscopic radical prostatectomy program. Pelvi-trainers allow training on the anastomosis technique, with reproducible results. This chapter presents the key points for laparoscopic vesico-urethral anastomosis.     

Histologic and prognostic study of nephroblastoma in central Tunisia

Nephroblastoma is a common malignant tumour in childhood that benefited from therapeutic progress. This is a retrospective study of 35 nephroblastoma diagnosed and treated in the central region of Tunisia within the last 8 years (1991-1999). We report and compare clinical features, therapeutic results and prognostic factors with those reported in the literature. The mean age was 3-years and 9 months, and the main clinical symptom was abdominal mass. Pre-operative chemotherapy was done in 32 cases and the objective response rate was 58%. Thirty-three patients had radical nephrectomy and only one had partial nephrectomy. Histologic analysis concluded to an anaplastic nephroblastoma in 2 cases. Using the classification of the international society of pediatric oncology, 11.4% of tumours were stage I, 48.6% stage II, 5.7% stage III, 11.4% stage IV and 2.9% stage V. The overall 5 years survival was 80%; tumour relapse was only independent prognosis factor in multivariate analysis (P < 0.01). Prognosis of nephroblastoma has been improved with chemotherapy and the pluridisciplinar treatment.     

Prostate cancer in the elderly patient

Although malignant tumours occur at all ages, cancer disproportionately strikes individuals in the age group 65 years and older. The increasing statistical life expectancy of men together with the introduction of prostate specific antigen (PSA) as a screening tool have both contributed to a rising number of elderly men with a diagnosis of prostate cancer. Age is generally considered to be a key prognostic factor in terms of therapeutic decision making, perhaps as important as PSA level and Gleason score. Even in men over 70 years, treatment without curative intent may deprive frail patients of years of life. When considering local treatment, strong consideration should be given to radical surgery. Modern radical prostatectomy is associated with low perioperative morbidity, excellent clinical outcomes as well as long term disease control. Besides, overdiagnosis has led to the concept of expectant management for screening-detected small-volume, low grade disease, with intention of providing therapy for those men experiencing disease progression.     

Screening for prostate cancer: arguments "against"

Prostate cancer screening is controversial since PSA assay has been made available. Screening supporters consider that early diagnosis allows better and less aggressive treatment. These arguments lie on longitudinal cohort studies without controls. Randomized studies are required to assess the correlation between screening and mortality lowering. Two studies are being performed and their results will be available within three or four years. Consequently, the validity of screening is unknown. Nevertheless, the analysis of various parameters demonstrates that the reduction of cancer mortality related to screening is low. According to these data and as recommended by health institutions prostate cancer screening is not required. At the present time, detection asked by the patient himself remains the good attitude between negligence and excessive attitude.     

Superficial pT1G3 bladder tumor: 24 case reports

The authors report 24 patients presenting a transitional tumor of bladder pT1G3 collected between January 1996 and December 2000. They represent 19% of the superficial tumors of bladder. Two patients had of straightaway a cystectomy after resection for an unverifiable tumor by endoscopy and another after a second resection discovering a real pT2. Only 5 patients received a BCG therapy is 24% of the cases. A recurrence without progression has been noted in 38% of the cases and a progression in 19% of the patients. These last patients had a cystectomy and with a follow-up to 28 months, no recurrence has been noted.