Fertility and Gonadal Function

Spermatogenesis is impaired in a substantial proportion of patients presenting with germ cell cancer. In normospermic men who undergo combination BEP chemotherapy, a reduction in fertility is apparent postchemotherapy, although for most individuals sperm counts will recover over a period of years 50 . Of note, a good prechemotherapy sperm count is associated with a increased likelihood of recovery of spermatogenesis. With regard to hormonal function, a comparison of patients treated with...

Perineal Prostatectomy

Retropubic prostatectomy continues to be undertaken with excellent results, though some surgeons prefer the perineal approach. The perineal approach avoids the bleeding sometimes encountered from the dorsal venous complex, as the prostate is removed behind this plane. As a result, the anterior surgical margin can be compromised, and this may have some adverse therapeutic significance in some patients, particularly those with extensive or anterior tumors. Complications specific to this approach...

Intermittent Hormonal Therapy

Among the most important quality of life issues for patients with prostate cancer is the loss of sexual function with treatment. For this reason many men delay treatment or take treatment intermittently. There is no evidence whatsoever that intermittent treatment is less successful than continuous therapy. Indeed, if one examines the effects of hormonal treatment on prostate cancer cells growing in culture, then a single exposure to antiandrogen therapy is seen to cause devastating destruction...

Combinations of Targeted and Cytotoxic Therapy

Targeted therapy in combination with chemotherapy is another area of active research. Several trials have assessed the combination of targeted therapies such as thalidomide, calcitriol, and exisulind with docetaxel. Thalidomide glutarimide is a synthetic glutamic acid derivative that was initially used for morning sickness but was taken off the market due to teratogenicity and neuropathies. Thalidomide has antiangiogenesis effects, inhibits cytokines including tumor necrosis factor-a, and can...

The Side Effects of Hormonal Therapy

In the treatment of any group of patients, there is a historical paradigm to clinical reportage. The initial publication describes an effect of a new treatment. The follow-up publications confirm this effect. A third group of publications then emerge comparing the effect of the new treatment to a standard therapy option, and then finally the side effects of the new treatment are reported. This has been the case with the hormonal treatment of prostate cancer. The initial reports of estrogen...

Neoadjuvant Chemotherapy

The use of systemic chemotherapy earlier in the course of treatment, an effective strategy in some malignancies, has been explored to a small degree in prostate cancer. The objectives of neoadjuvant chemotherapy are to downstage the cancer, decrease the incidence of positive surgical margins, and eliminate micro-metastases. In addition, chemotherapy may eradicate both androgen-independent clones and androgen-sensitive clones, the latter by synergizing with hormonal ablation. Several pilot...

Principles of Radical Prostatectomy

Radical prostatectomy is generally carried out with the intent of achieving long-term disease-free survival and thereby cure of early-stage prostate cancer 20 . Secondary, but nevertheless important, concerns are the maintenance of quality of life, in particular continence and erectile function. In some countries, interest is growing in a potentially palliative role in patients with more advanced and noncurable disease. Favorable long-term survival in patients with pathologically organ-confined...

The Hormonal Treatment of Locally Advanced and Metastatic Prostate Cancer

The history of hormonal therapy for prostate cancer dates back to the 1890s, when patients with prostatic diseases, which included cancer, were treated by orchiectomy, and their condition improved. Scientific analyses of the results of treatment emerged nearly a century later, and, after enormous resistance from the urological surgical community, medical therapies for prostate cancer began to replace orchiectomy as a standard treatment for the condition. The urologists argued from the surgical...

The Treatment of Recurrent Prostate Cancer

There is clinical evidence of prostate-specific antigen (PSA) progression after a median period of 13 months' hormonal therapy. Some 2 years after this evidence emerges, clinical symptoms develop, to be followed a median of 7 months later by death, and this course of events is not what we want for our patients. The biological basis for relapse is of more than passing interest. If patients' biopsy specimens are compared at presentation and relapse, mutations are seen within the androgen receptor...

Combined Antiandrogen Treatment

Labrie, a French Canadian, has made a great contribution to prostate cancer treatment, and suggested that in a disease that is androgen sensitive it is important to eliminate all sources of androgen. Labrie advocated the use of a combination of an antiandrogen with an LHRH agonist in the treatment of prostate cancer. The sources of androgen supplied to the prostate are dietary, adrenal, and testicular. The use of an antiandrogen, such as flutamide, potentially has the benefit of acting...

Other Cytokines

Several other interleukins (for example IL-1, -4, and -6) have been tested in phase I and II trials in renal cell carcinoma, but antitumor activity has been low, with response rates of less than 5 . One of the more promising new agents is IL-12, which promotes cell-mediated immunity through its regulatory effects on T and natural killer (NK) cells. In a randomized phase II trial of IL-12 versus IFN-a in advanced renal cell carcinoma, 30 patients were treated with IL-12 and 2 (7 ) achieved a...

Attempts to Improve MVAC

In an attempt to decrease the toxicity and enhance the efficacy of MVAC, several investigators evaluated the use of altered doses and schedules with granulocyte colony-stimulating factor (GCSF) support. Based on the potential for enhanced survival conferred by greater drug delivery, the European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial comparing MVAC administered every 2 weeks (with GCSF) with MVAC administered every 4 weeks 8 . Although this...

Interleukin2 and Interferona

Synergistic antitumor effects of combining IL-2 and IFN-a are seen in murine tumor models and provide a rationale for their use in the clinical setting. The exact mechanisms of synergy are unknown, but it is possible that administration of IFN-a may increase the immunogenicity of tumor cells via an enhancement of their histocompatibility and tumor-associated antigens, thus increasing their lysis by CTLs, the number of which are increased by IL-2. Clinical trials investigating IFN-a and IL-2...

Introduction

Bladder cancer is the fourth most common cancer in men and the eighth most common cancer in women worldwide, and the incidence continues to rise. In the United Kingdom, 13,600 new cases per annum contribute 5 to the national cancer burden 1 . Over 100,000 diagnostic, check, and interventional cystoscopies each year are performed in surveillance protocols in attempting to monitor for disease progression. In the United States, there were approximately 57,500 new cases and 12,500 deaths in 2003,...

Carcinoma in Situ CIS

Carcinoma in situ is defined as a flat (nonpapillary) high-grade transitional cell carcinoma that has not penetrated the basement membrane of the epithelium. Such lesions are considered distinct entities from papillary (pTa pT1) tumors, with profound implications for prognosis. Clinically, CIS can be divided into diffuse (velvety erythematous elevations) or focal (thickened white metaplasia) lesions. Diffuse CIS is nearly always reflected in filling (storage) bladder symptoms and positive urine...

Angiogenesis Inhibitors

Angiogenesis is the growth of new microvessels. The growth of tumors beyond 1 to 2 mm3 depends on angiogenesis,which is necessary for the supply of nutrients and also provides a route for metastasis. In adults the vascular endothelium is a quiescent tissue with a low cell division rate, and thus pathological angio-genesis must occur to allow tumor development. A number of proangiogenic factors (e.g., basic fibroblast growth factor and vascular endothelial growth factor VEGF ) have been...

Tumor Products

Cellular material for therapeutic use can also be obtained directly from the tumor. As mentioned above, tumor material can be used to obtain peptide, nucleic acid, or other material for loading into dendritic cells. Tumor cell material may also be used without ex vivo dendritic cell loading. Presumably antigen presentation can occur in vivo with either the modified tumor cell acting as substitute antigen-presenting cell, or attracting autologous dendritic cells that then take up the relevant...

Adjuvant Therapy

The only curative treatment for renal cell carcinoma is complete surgical excision of the primary lesion. As stated earlier, 20 to 30 of patients who initially present with localized disease subsequently relapse after nephrectomy, usually with metastatic disease . Thus there is a need for an effective adjuvant therapy. Three large randomized trials totaling 250 patients have compared adjuvant interferon with observation in resected Robson stages II (perinephric fat involved) and III (tumor...

Prognosis

In patients with early-stage disease, there are few deaths due to penile cancer and the long-term overall survival rates are often determined by the comorbid conditions in an elderly population 28,31,86 . Depending on the proportion of cases in different stages, 5-year penile cancer-specific survival rates of 66 to 88 have been reported 28,31,86 . Of the few large studies with multivariate analysis of prognostic factors, nodal metastases 9,19,31 , higher T stage or invasion 9,31,48 , and high...

Angiogenic Targeting

Renal cancer specimens are often observed to be densely vascularized reports of difficult-to-control bleeding during surgery on metastases (as opposed to nephrectomy, where the renal vascular stalk is a point of control) are common. The concept of targeting the blood vessels of the cancer is appealing for several reasons low toxicity, conversion of the disease to a chronic pattern, and an independent attack at a fundamental vulnerability of the growing tumor. The genotype of the targeted cell...

Contralateral Testicular Biopsy

Carcinoma in situ (intratubular germ cell neoplasia ITGCN ) consists of atypical cells located in a single row at the basement membrane of seminiferous tubules. It is universally detected in the tissue surrounding germ cell tumors 7 . These cells are the uniform precursor of all germ cell neoplasms of the testis (other than spermatocytic seminoma) and develop during embryogen- esis. Cellular proliferation then probably occurs during and after puberty 8 . Usually all spermatogenic cells are...

New Active Single Agents

Given the limitations with MVAC therapy, new agents had to be developed to improve long-term outcome and reduce toxicity. Recently, several agents with activity in TCC have been identified. These new agents differ from the older drugs in that they demonstrate moderate activity as both first-line and second-line therapy, more favorable toxicity profiles, and a drug metabolism that is independent of renal excretion. Of these newer agents, the most extensively studied have been gemcitabine, the...

Role of Intravesical Therapy in Tumor Prophylaxis

The purpose of intravesical adjuvant therapy is threefold to eradicate residual tumor, to reduce the rate of recurrence, and to reduce the risk of tumor progression. Many different topical instillation agents have been proposed and tried over three decades. However, only two classes of cytotoxic agent and one immunotherapeutic modulator have been established with (limited) clinical efficacy, and are in common use. These are the anthracycline antibiotics Adriamycin and epirubicin, the...

Natural History Histology and Clinical Presentation

Penile cancers are diagnosed often in the fifth to seventh decade in the West 3 ,but in high incidence areas,the disease often manifests one to two decade earlier 2,6,7 . The disease starts from the glans, corona, or prepuce, but in certain parts of the world where delayed presentation is common, the majority of patients have tumor extension to penile shaft or groin nodes at the time of diagnosis 7 . A vast majority of these invasive cancers are squamous carcinomas or their variants such as...

Estramustine TaxaneBased Therapy

Estramustine phosphate, a conjugate of estradiol and nitrogen mustard, with hormonal and nonhormonal cytotoxic effects in vitro, has also been evaluated in HRPC 22 . Unlike other alky-lating agents, estramustine does not directly damage DNA but depolymerizes cytoplasmic microtubules and microfilaments, binds to microtubule associated proteins, disrupts the nuclear matrix, and inhibits P-glycoprotein 23 . Based on in vitro data suggesting synergy, several phase II studies have been completed...

Interleukin2

Interleukin-2 (IL-2) is the other cytokine that has shown significant activity against renal cell carcinoma. IL-2 is produced primarily by T cells it has no intrinsic antitumor activity, but it has a wide range of actions and plays a central role in immune regulation. Its primary action is to stimulate growth of activated T cells that bear the IL-2 receptor it also potentiates the activity of cytotoxic T cells and production of other cytokines. The initial work on IL-2 was carried out by...

Laparoscopic Prostatectomy

Laparoscopic radical prostatectomy has developed within the past 10 years, recognizing the many potential benefits of laparoscopic surgery. It was first described by Schuessler et al. 10 in 1992, and at that time presented significant challenges 11 . Reduction in the extent of surgical incisions, postoperative pain, and analgesic requirement, and shorter convalescence including reduced hospital stay contribute to its potential advantages. Disadvantages relate to the considerable specific skills...

Retropubic Prostatectomy

The retropubic approach to radical prostatectomy did not develop until Terence Millin's description of his now classical operation for benign disease, the transcapsular prostatectomy. He adapted this operation to total (radical) prostatectomy, which had not been possible with the transvesical procedures with which surgeons had hitherto become familiar 3 . During the ensuing years, the perineal and retropubic approaches for radical prostatectomy each had its advocates. Radical prostatectomy...

New Cisplatin Triplets

The combination of ifosfamide, paclitaxel, and cisplatin (ITP) has been studied in a phase II trial 19 . Myelosuppression was the predominant toxicity (45 grade 3 to 4 neutropenia), although the risk of febrile neutropenia was low (3.3 of all cycles). Grade 3 neuropathy and renal insufficiency occurred in 9 and 11 , respectively. Thirty of 44 assessable patients (68 95 CI, 52-81 ) achieved a major response, with 10 complete responses (23 ) and 20 partial responses (45 ). The reported median...

Poor Prognosis Disease Table

This is a comparatively uncommon group, and trial accrual has historically been slow. In general, studies in this group have used four cycles of American BEP500 as a control, comparing this with a more intensive treatment in the remaining arm of the study. In an early intergroup study from Indiana University, 159 patients with advanced metastatic disease by Indiana criteria were randomised to receive four cycles of American BEP500 or the same regimen with double-dose cisplatin (40mg m2 IV daily...

Carboplatin Compared to Cisplatin

Despite the similar response proportions of single-agent carbo-platin compared to single-agent cisplatin, controversy still exists regarding the relative value of carboplatin in TCC, particularly in combination regimens. The randomized phase II trials exploring combination regimens with cisplatin compared to carboplatin consistently report higher overall and complete response rates for the cisplatin-containing regimens 32,35,36 . Consequently, in patients with advanced TCC without absolute...

Nodal Metastasis

Like all squamous carcinomas, penile cancers have a propensity for lymphatic spread to the draining lymph nodes in the superficial and deep inguinal region and later to the iliac chain. Skip metastasis to the iliac nodes is very unusual 12,13 . Lymphatic spread is uncommon in the verrucous cancers of the penis 9,11 . For invasive squamous carcinomas, the risk of nodal metastases increases with increasing depth of invasion 12-14 , Table 11.1. Incidence of nodal metastasis for different T stage...

Epidermal Growth Factor Receptor Inhibitors

The epidermal growth factor receptor (EGFR) superfamily of receptors, which comprises four distinct receptors known as EGFR, Human Epidermal growth Factor Receptor, HER2, HER3, and HER4, is a potential therapeutic target in prostate cancer where overexpression is seen in up to 80 of metastasis, and is generally associated with a poorer overall prognosis. Several EGFR targeting agents are now available, including tyrosine kinase inhibitors and monoclonal antibodies. To date, the tyrosine kinase...

Conclusion

Many patients with bladder cancer are elderly, with extended comorbidity, and a careful ap-proach to their treatment is necessary. Atten-tion to and accurate documentation of relevant clinical and histopathological prognostic factors allows stratification into low-, intermediate-, and high-risk groups. Diffuse carcinoma in situ is considered a separate and aggressive disease cat-egory. The timing of future surveillance cys-toscopy and interventional adjuvant therapy are dependent on these...

Hormone Refractory Prostate Cancer

Hormone-refractory prostate cancer is defined as disease that progresses despite castrate testosterone levels, and is refractory to all hormonal manipulations including withdrawal of antian-drogen therapy. Until recently, there had been no standard chemotherapeutic approach for HRPC. Several agents had been evaluated in clinical trials, but many older studies suffered from methodological deficits such as small numbers of patients, heterogeneity of enrolled patients, and lack uniform response...

Current Issues in Superficial Bladder Cancer Classification

The current system of bladder tumor classification is based on the International Union Against Cancer (UICC) revision of 1997 4 . Superficial bladder cancer is the term used to describe transitional cell carcinomas with histopathological categories pTa and pTl as well as carcinoma in situ (CIS) pTa tumors are confined to the urothelium bordered by the basement membrane, whereas pT1 tumors have penetrated into the lamina propria. Much debate has been concerned with the inclusion of pT1 tumors as...

New Carboplatin Triplets

Several carboplatin triplets have been studied including pacli-taxel plus carboplatin plus methotrexate 33 , paclitaxel plus carboplatin plus gemcitabine 34 , and methotrexate plus carboplatin plus vinblastine (M-CAV) 35 . In general, these regimens have been associated with slightly higher response proportions and slightly increased toxicity compared with historical trials of carboplatin doublets. No phase III trials have explored the activity of these triplets relative to standard therapy.

Natural History of Superficial Bladder Cancer and Prognostic Factors

Because the type and timing of adjuvant therapy for superficial bladder cancer depends on the prediction of biological change from an indolent to an aggressive phenotype, a good understanding of the natural history of the disease is essential for the working practice of urologists and oncologists. Because even patients with low-grade, low-stage superficial bladder cancers are now subjected to adjuvant therapy, contemporary data of untreated tumors are sparse. This is of particular relevance to...

Stromal Tumors

Can be cured by orchidectomy, but approximately 10 have metastatic potential. In contrast with treatment for germ cell tumors, treatment for metastatic stromal tumors is not very effective. Patients with a malignant stromal tumor that metastasizes survive on average only 3 years from diagnosis. In addition, it is difficult to identify high-risk patients who might benefit from more intensive treatment or surveillance, as there are no consistently reliable histolog-ical indicators of malignant...

The Impact of Prognostic Factors

Pretreatment prognostic factors play a key role in predicting the outcome of patients with advanced TCC treated with MVAC and other cisplatin-based regimens. In a retrospective analysis, a database of 203 patients with unresectable metastatic TCC was subjected to multivariate analysis to determine which patient characteristics predicted survival 9 . Two factors had independent prognostic significance Karnofsky performance status (KPS) < 80 and visceral (lung, liver, or bone) metastases. The...

Urological Cancers in Clinical Practice

Urological Cancers in Clinical Practice Urological Cancers in Clinical Practice Jonathan Waxman, BSc, MD, FRCP Professor of Oncology Department of Oncology, Division of Surgery, Oncology Reproductive Biology and Anaesthetics (SORA) Faculty of Medicine, Imperial College London The Garry Weston Centre, Hammersmith Hospital, London, UK Chapters 1-7 and 9-11 reproduced, with updates, from chapters 5, 7, 8,9, 13, 14, 17,20,21, and 24, respectively in Waxman J. Urological Cancers, 2005 SpringerVerlag...

Intravesical Immunotherapy and Recurrence Progression Rates

Intravesical immunotherapy using BCG was first proposed by Morales et al. 49 in 1976. Conventional prophylactic regimes of 6 weekly instillations, similar to those used for chemotherapy, resulted in complete response rates of 60 to 100 at 1 year, 55 to 75 after 2 years, and mean recurrence-free intervals of 10 to 22.5 months 50 . Although the long-term response rates with BCG are less enduring, the reduction in recurrence appears to be better than the rates achieved using most chemotherapy...

Nonseminomatous Germ Cell Cancer

Approximately 40 of men presenting with testicular nonsemi-nomatous germ cell cancer have stage I disease (normal staging on a computed tomography CT scan, normal tumor markers, or markers that normalize following orchidectomy) with an anticipated risk of systemic relapse of 25 for patients followed by surveillance. Histopathological examination of the resected testis enables stratification of patients with stage I disease into two groups at low or at high risk of relapse. Combined data from...

Relative Risk of Clinical Prognostic Factors

The factors that predict the biological potential of superficial lesions must be correctly weighted before deciding on cysto-scopic surveillance protocols and adjuvant therapy. The relative importance of the prognostic factors was measured by multi-variate analyses of two Medical Research Council (MRC) trials 26 and two EORTC-GU trials 20 . In the MRC analyses, tumor number at presentation and tumor recurrence at the first follow-up cystoscopy at 3 months were statistically better at predicting...

Targeted Drugs

Targeted drug therapy has become the watchword of the pharmaceutical industry in the new millennium. Isolated successes such as rituximab for non-Hodgkin lymphoma or imatinib mesy-late in chronic myelogenous leukemia are a basis for hope that each cancer will have a pharmacogenomically discoverable Achilles' heel, susceptible to the right target targeted drug combination, with inconsequential toxicity. The targets of renal cancer remain elusive. Pathophysiological studies highlight the pathway...

References

Chemotherapy for renal cell carcinoma. Semin Oncol 2000 27(2) 177-16. 2. Fishman M, Antonia S. Novel therapies for renal cell carcinoma an update. Expert Opin Investig Drugs 2003 12(4) 593-609. 3. Rini BL, Vogezang NJ, Dumas MC, Wade JL, Taber DA, Stadlet WM. Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J Clin Oncol 2000 18(12) 2419-2426. 4. Ryan CW, Vogezang NJ, Stadler WM. A phase II trial of...

Quality of Life and Psychosexual Issues

These issues, unfortunately, have been entirely neglected in most reports on penile cancer. This is surprising considering the possible major psychosexual impact of a penectomy. There are only a few small, mostly retrospective studies evaluating the quality of life and psychosexual issues (2,88,89). The expected quality of life, particularly sexual functions after treatment, should be specifically discussed with the patient. It is an expansive concept that involves vast and profound evaluation....

Pretreatment Evaluation and Pitfalls in Staging

For optimum management using the most appropriate treatment approach and ensuring best outcome, a simple but systematic pretreatment evaluation is mandatory. A careful history and interview should also include a history of sexual practices, sexually transmitted disease, chronic inflammatory penile conditions, and the likely psychosexual impact of a penectomy if recommended. The location, type, size, and extension of the tumor, presence of any premalignant or inflammatory condition, infection,...

Impalpable or Clinically Insignificant Groin Nodes

In patients with impalpable or clinically insignificant groin nodes with a negative FNAC, there is no consensus regarding selection of patients for close surveillance, sentinel node biopsy, or groin node dissection. Because clinical examination, imaging, and FNAC may miss subclinical nodal metastasis in up to 20 patients 3,24 , special diagnostic procedures such as sentinel node biopsy or limited surgery to identify occult metastases and prophylactic node dissection have been evaluated by...

Treatment Options in G3pT1 Disease

G3pT1 forms the watershed of therapeutic intervention, with advocates of conservative and radical intervention equally persuaded in their differing interpretation of the available data. The historical series suggest that untreated G3pT1 has a recurrence rate between 70 and 80 , and progression rates ranging from 29 to as high as 50 74 . In Birch and Harland's 75 review, 40 of G3pT1 cases followed beyond 24 months developed muscle-invasive disease. Although it is now accepted that treatment with...

Penile Conservative Therapy

Because amputative surgery for penile cancer may lead to major psychosexual dysfunction, various attempts have been made to devise conservative treatment modalities based on careful oncological, anatomical, and technical considerations. Judicious use of conventional or micrographic surgery, laser ablation, or radiotherapy can allow preservation of a functioning phallus in appropriately selected patients with early cancers. However, there are no comparative studies and no consensus regarding the...

Role of Bacille Calmette Gurin in the Treatment of Carcinoma in Situ

To date, BCG remains the treatment of choice for CIS disease. Although cytotoxic chemotherapy agents have shown initial response rates as good as 48 using anthracyclines and 53 for MMC, most series have demonstrated that this response is time limited, with fewer than 20 remaining disease free at 5 years 72 . This apparent chemoresistance may well reflect the high grade of CIS disease, whereas higher grade may imply greater antigenicity and therefore susceptibility to BCG immunotherapy. Bacille...

Contributors

Abel, ChM, FRCS Department of Surgery Faculty of Medicine Hammersmith Hospital Campus Imperial College London London, UK Genitourinary Medical Oncology Service Department of Medicine, Solid Tumour Oncology Memorial Hospital for Cancer and Allied Diseases Memorial Sloan-Kettering Cancer Center New York, NY, USA Simon Chowdhury, MB BS Department of Medicine Royal Marsden Hospital London, UK Timothy J. Christmas, MD, FRCS Urol Department of Urology Imperial College School of Medicine...