FOLLOW-UP STRATEGIES AND MANAGEMENT OF RECURRENCE IN UROLOGIC ONCOLOGY. Preface Dan Theodorescu

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1 FOLLOW-UP STRATEGIES AND MANAGEMENT OF RECURRENCE IN UROLOGIC ONCOLOGY Preface Dan Theodorescu xv Populations at High Risk for Prostate Cancer 669 Kisseng Hsieh and Peter C. Albertsen Although prostate cancer tends to be a slow-growing neoplasm affecting primarily older men, there is clearly a subset of younger patients at high risk of developing clinically significant disease. This group of patients includes men with a familial history of prostate cancer. Despite significant progress in identifying genetic markers for this disease, no single prostate cancer gene has been identified. Furthermore, the presence of multiple genetic markers suggests a strong environmental component to the development of prostate cancer. The high incidence of this disease among African Americans and the relatively low incidence among Asian Americans strongly suggest that diet may play an important role. The Western diet is much higher in fat and red meat compared with the Asian diet. Furthermore, soy-based diets appear to have an anticancer effect. Men who undergo transrectal ultrasound and prostate biopsy who are found to have highgrade prostatic intraepithelial hyperplasia or atypical small acinar proliferation also have a significantly higher risk of being diagnosed with prostate cancer. Screening men at increased risk of developing clinically significant disease appears to be a logical strategy, especially in light of recent reports that suggest a benefit to aggressive treatment. PSA Markers in Prostate Cancer Detection 677 Matthew B. Gretzer and Alan W. Partin The prostate-specific antigen (PSA) revolution that has occurred over the previous 2 decades has positively impacted the detection and treatment of men with prostate cancer. Although methods to improve specificity have shown promise (eg, PSA density, agespecific PSA, and PSA velocity), meaningful interpretation has yet to be uniformly accepted within clinical practice. The identification of other molecular forms of PSA within serum has led to a new era in PSA markers. Initial application employing the percentage of free to total PSA has provided improved discrimination between benign and malignant prostatic disease; however, questions remain regarding the ultimate threshold value. The discovery of various free forms of PSA such as propsa, benign PSA, and intact PSA also have introduced the potential for improved specificity in detection. Although early results are encouraging, further evaluation is anticipated. The development of improved methods to detect and measure complexed PSA has demonstrated provocative results, and exhibits the potential to replace PSA as a standard diagnostic test in cancer screening. VOLUME 30 Æ NUMBER 4 Æ NOVEMBER 2003 vii

2 Follow-up of Conservatively Managed Prostate Cancer: Watchful Waiting and Primary Hormonal Therapy 687 Edward M. Messing and Ian Thompson Jr. Many men with newly diagnosed prostate cancer choose not to undergo curative treatment, including patients who cannot be helped by local curative therapies (especially those with metastatic disease) and patients with clinically localized disease who opt for expectant management or noncurative treatments such as androgen ablation. This article reviews the selection of patients for these noncurative approaches, strategies for clinical monitoring, the choices of intervention therapies upon progression, and when to start these therapies. Prostate Cancer: Radical Prostatectomy 703 Joel B. Nelson and Herbert Lepor Today, more men than ever before are being followed after radical prostatectomy. Prognosis and follow-up should be based on the pathologic specimen. Measurable prostatespecific antigen (PSA) after surgery defines failure, with time to detectable PSA and rate of PSA rise being useful prognostic factors. The natural history of untreated biochemical failure is protracted, a fact to be considered in discussions of adjuvant treatment. Early in disease recurrence, imaging studies to locate residual disease rarely are useful clinically. Both adjuvant and salvage radiation to the prostate bed have benefits and risks, but neither is superior in overall prostate cancer survival. The timing of hormone therapy remains largely empiric. The promise of effective cytotoxic chemotherapy still is greater than its actual benefits, although novel cytostatic agents are being developed. The future management of this disease will improve with better molecular definition of risk and therapeutic response. Prostate Cancer: Cryotherapy 725 Katsuto Shinohara The incidence of prostate cancer has more than doubled in the last 10 years, and 220,900 new cases will be detected in This increase is due in large part to increased use of prostate-specific antigen (PSA)-based screening, transrectal ultrasonography, and random biopsy of the prostate. The treatment of prostate cancer, however, remains controversial, and no consensus has been established as to what constitutes appropriate treatment for any stage of disease, especially for localized cancers. Radical prostatectomy, radiation therapy, or watchful waiting all have their advocates, and the risks and benefits of these approaches are discussed frequently. Skepticism about conventional treatments has stimulated patients and physicians to search for alternatives that are effective and associated with limited morbidity. Technologic developments have rekindled interest in cryotherapy as a viable alternative to other, more conventional localized therapies. Given the relative paucity of alternatives for patients who experience biochemical progression after radiotherapy, cryosurgery also may prove to be a good alternative for those patients whose tumors appear to remain localized despite progression. In addition, it appears that cryosurgery will play an increased role in the future management of prostate cancer. Brachytherapy for Prostate Cancer: Follow-up and Management of Treatment Failures 737 Eric M. Horwitz, Robert G. Uzzo, Nicole Miller, and Dan Theodorescu The use of prostate brachytherapy for the treatment of early-stage, low-grade, lowvolume carcinoma of the prostate continues to rise. Given the prolonged natural history of these early lesions, treatment failures may take many years or even a decade or more viii

3 before becoming clinically evident. It is therefore likely that as the brachytherapy data mature, clinicians will be asked to help manage a potentially large cohort of men who have failed this local therapy a scenario that will provide a number of unique challenges for the treatment of the disease and the management of the lower urinary tract. This article offers a contemporary review and suggestions with regard to the follow-up of patients who have undergone prostate brachytherapy, including low-dose rate permanent implants and high-dose rate temporary implants for the management of localized prostate cancer. In addition, current controversies in defining biochemical failure following radioactive implantation including important data regarding the prostate-specific antigen bounce phenomenon are discussed. Finally, a comprehensive review of the management of local recurrence following brachytherapy is offered. Recurrent Prostate Cancer Following External Beam Radiotherapy: Follow-up Strategies and Management 751 Charles Catton, Michael Milosevic, Padraig Warde, Andrew Bayley, Juanita Crook, Robert Bristow, and Mary Gospodarowicz A sound follow-up strategy after radical radiotherapy (RT) for localized prostate cancer is needed to improve individual treatment results by providing accurate information about local relapse and complication rates. In addition, early detection of recurrence provides opportunities for re-treatment and salvage of a local or systemic relapse. Prostatespecific antigen (PSA) level determination is the mainstay of post-rt follow-up, and periodic measurement of post-rt PSA kinetics is the established surrogate method of determining post-rt outcome and should be continued for life. Posttreatment sextant biopsies performed 2 to 3 years after RT provide pathologic evidence of local tumor control and a positive posttreatment biopsy is a must before considering local ablative salvage therapy. Although hormonal therapy remains the standard treatment of clinical or biochemical relapse following radical RT, local salvage therapy given with curative intent should be considered in selected individuals with biopsy-proven local relapse. Evaluation and Follow-up Strategies for Superficial Bladder Cancer 765 S. Machele Donat Superficial bladder cancer comprises about 80% of patients presenting with bladder cancer to the practicing urologist. The risk of tumor recurrence is dependent on tumor stage, tumor grade, number of tumors (multifocality), the presence of associated carcinoma in situ, and the initial response to therapy. Clinical staging and completeness of resection of the primary tumor are essential in treatment planning, predicting the risk and site of recurrent disease, and determining follow-up strategies. The increasing frequency of extravesical recurrences over time requires continued observation of the upper tracts and prostatic urethra. Due to the panurothelial nature of the disease and lifelong risk of recurrence, surveillance should continue for the lifetime of the patient. Follow-up Strategies and Management of Recurrence in Urologic Oncology Bladder Cancer: Invasive Bladder Cancer 777 Bernard H. Bochner, James E. Montie, and Cheryl T. Lee A surveillance program following cystectomy should consider a patient s individual risk for the development of local and distant recurrences and any specific needs related to the urinary tract reconstruction performed. Well-documented recurrence patterns following cystectomy are available from many large surgical series and provide the background information needed for tailoring follow-up based on pathologic criteria. Economic issues also must be considered, given that the health care related expenses of treating and ix

4 following patients with bladder cancer is twice as much as that expended for the treatment of prostate cancer. Because of the ever-increasing fiscal constraints placed on clinicians, risk-adjusted follow-up strategies are reasonable, but will require prospective evaluation to validate their appropriateness. Surveillance and Management of Recurrence for Upper Tract Transitional Cell Carcinoma 791 Steven E. Canfield, Colin P.N. Dinney, and Michael J. Droller This article reviews the natural history of upper tract transitional cell carcinoma (TCC) to identify risk factors and patterns of recurrence, which in turn identify potential targets for surveillance. Technologic advances in the field are changing the management and follow-up of patients with upper tract TCC. Current surveillance tools are reviewed, and surveillance strategies and management of recurrence are discussed. Management of Recurrence and Follow-up Strategies for Patients with Seminoma and Selected High-risk Groups 803 Manish I. Patel, Robert J. Motzer, and Joel Sheinfeld Seminoma is characterized by high sensitivity to both radiation and chemotherapy. Localized recurrences in the retroperitoneum after surveillance for stage I can be treated with radiotherapy; however, multiple or large bulky retroperitoneal recurrences or systemic metastasis require cisplatin-based chemotherapy. Salvage chemotherapy for those patients who recur after initial complete response to induction chemotherapy is based on regimens containing ifosfamide and cisplatin. Incomplete response or failure after induction chemotherapy requires high-dose chemotherapy and stem-cell rescue. Patients with seminoma require long-term follow-up because of the possibility of late recurrence and the risk of a contralateral primary tumor. Management of Recurrence and Follow-up Strategies for Patients with Nonseminoma Testis Cancer 819 Michael A.S. Jewett, Arthur Grabowski, and James McKiernan This review serves as an outline of the clinical features and management options for the majority of recurrence situations in nonseminoma germ cell tumors (NSGCTs). The combination of reliable serum tumor markers, improved imaging techniques, effective cisplatin chemotherapy regimens, and application of meticulous surgical techniques has resulted in dramatic improvements in cure rates in NSGCTs. These factors have caused the incidence of recurrent NSGCTs to decline substantially in the past 20 years. This rarity of recurrence in combination with the low incidence of NSGCTs prevents the practicing clinician from accumulating experience in this challenging patient population. Therefore, to ensure improvement in salvage rates, patients are best managed in centers with extensive experience in NSGCTs. Hereditary Kidney Cancer 831 Jonathan J. Hwang, Edward M. Uchio, W. Marston Linehan, and McClellan M. Walther Patients with hereditary renal cancer syndromes may be predisposed to the development of multiple bilateral renal tumors and can face a lifelong risk of tumor recurrence. Understanding of the genetic basis of hereditary syndromes has led to early screening of families at risk and improved disease management. In addition, the identification of molecular pathways in hereditary settings has given insights into tumoriogenesis of sporadic renal cancers. x

5 Surveillance After Radical or Partial Nephrectomy for Localized Renal Cell Carcinoma and Management of Recurrent Disease 843 Nicolette K. Janzen, Hyung L. Kim, Robert A. Figlin, and Arie S. Belldegrun Surveillance after surgery for renal cell carcinoma is important because approximately 50% of these patients will develop a disease recurrence, two thirds of who will recur within the first year. Although the prognosis is generally poor in these patients, some may respond favorably to immunotherapy. The small subset of patients who develop solitary metastases has the greatest chance to achieve long-term survival. Aggressive surgical resection is an integral part of this success. Proposed surveillance protocols using a stage-based approach or an integrated approach combining stage with other important prognostic factors attempt to provide a rational approach to identifying treatable recurrences while minimizing unnecessary examinations and patient anxiety. However, strict adherence to follow-up guidelines may not be appropriate for all patients. Factors including patient comorbidities and patient willingness to pursue aggressive management in the event of recurrence may alter the follow-up for each individual. Natural History, Management, and Surveillance of Recurrent Squamous Cell Penile Carcinoma: A Risk-based Approach 853 Ricardo F. Sánchez-Ortiz and Curtis A. Pettaway For men with premalignant penile lesions and those with preinvasive or invasive squamous cell penile malignancies, surveillance strategies should be tailored to the risks of local and regional recurrence. These vary according to the pathologic characteristics of the primary tumor and the modalities employed for local (phallus sparing or extirpative) and regional therapy (surveillance or lymphadenectomy). Men at a higher risk for local or regional recurrence who should be considered for more rigorous follow-up include (1) those treated with phallus-sparing strategies such as laser ablation, topical therapy, or radiotherapy; (2) those with clinically negative inguinal lymph nodes who are managed without lymphadenectomy despite high-risk primary tumors (pt2 3, grade 3, vascular invasion); and (3) those with lymph node metastases after lymphadenectomy. Good candidates for less-stringent surveillance include men with low-risk primary tumors (ptis, pta, pt1, grades 1 2) and patients with negative inguinal nodes after lymphadenectomy whose primary tumors were managed with partial or total penectomy. Follow-up and Management of Recurrent Wilms Tumor 869 Farzeen Firoozi and Barry A. Kogan An important aspect of the treatment of children with Wilms tumor is the follow-up and management of relapse. Through review of the National Wilms Tumor Studies, a comprehensive guideline has been created. In addition, common posttreatment sequelae involving multiple organ systems have been described. The prognosis for patients with relapse of Wilms tumor has been determined and new treatments are being developed. Perhaps the area most in need of in-depth focus is the treatment of patients with highrisk disease, particularly those with anaplastic disease, rhabdoid tumors, or clear cell sarcoma of the kidney. All of the above are discussed in this review. Neuroblastoma: Management, Recurrence, and Follow-up 881 Keith L. Lee, Jian F. Ma, and Linda D. Shortliffe Neuroblastoma is a neoplasm that affects infants and children with significant mortality and morbidity. Efforts at population-based screening have increased disease detection, but have failed to reduce mortality. The clinical behavior is highly variable, depending xi

6 on the patient s age, disease stage, and histopathologic findings. Research also has identified molecular markers that are useful in predicting disease aggressiveness and prognosis. By categorizing patients into risk groups, it is possible to optimize treatment and follow-up strategies. Low-risk patients may be amenable to observation or surgery alone, whereas multidisciplinary treatment protocols are needed in those with advanced disease and relapses. Although outcomes of patients with advanced disease remain poor, novel developments in research and treatment protocols are ongoing and hold promise to improved outcomes. Cumulative Index xii