Tumor markers in urology pdf

It is not certain whether it is as sensitive as cystoscopy. Most experts still recommend cystoscopy for diagnosis andMost experts still recommend cystoscopy for diagnosis and follow-up of bladder cancer. CA CA Glycoprotein normally expressed inGlycoprotein normally expressed in coelomiccoelomic epitheliumepithelium during fetal development.

Benign conditions- Uterine fibroidsBenign conditions- Uterine fibroids EndometriosisEndometriosis rupture ectopic pregnancy,rupture ectopic pregnancy, peritonitis, appendicitisperitonitis, appendicitis CA is the standard tumor marker used to follow womenCA is the standard tumor marker used to follow women during or after treatment for epithelial ovarian cancer theduring or after treatment for epithelial ovarian cancer the most common type of ovarian cancer.

High preoperative CA levels correlate with advancedHigh preoperative CA levels correlate with advanced stage III or IV and high grade disease, serous histology, andstage III or IV and high grade disease, serous histology, and the presence of ascites, but they are not a reliable predictor ofthe presence of ascites, but they are not a reliable predictor of the likelihood of optimal cytoreductionthe likelihood of optimal cytoreduction Ca Ca Benign conditions:Benign conditions: benign breast conditionsbenign breast conditions chronic hepatitis, cirrhosis,chronic hepatitis, cirrhosis, sarcoidosis, TB, SLEsarcoidosis, TB, SLE CA is used to monitor response to treatment, to detectCA is used to monitor response to treatment, to detect recurrence early more sensitive than CEA recurrence early more sensitive than CEA Most sensitive in all stages of Breast CancersMost sensitive in all stages of Breast Cancers Especially useful inEspecially useful in recurrent Breast cancer casesrecurrent Breast cancer cases CA CA It has a reported sensitivity and specificity of 80 to 90 percentIt has a reported sensitivity and specificity of 80 to 90 percent It has been proposed to differentiate benign from malignantIt has been proposed to differentiate benign from malignant pancreatic disease, but this capability remains to be establishedpancreatic disease, but this capability remains to be established sensitivity and specificity of 77 and 87 percent, respectively.

It will not usually detect very early disease. But it is nowIt will not usually detect very early disease. But it is now considered the best tumor marker for following patients withconsidered the best tumor marker for following patients with cancer of the pancreas. CA can also be used to monitor colorectal cancer, butCA can also be used to monitor colorectal cancer, but because it is less sensitive than the CEA test, most medical groupsbecause it is less sensitive than the CEA test, most medical groups recommend CEA testing when following this disease instead.

CalcitoninCalcitonin is a hormone produced byis a hormone produced by parafollicular C cells of thyroidparafollicular C cells of thyroid glandgland It helps regulate blood calcium levels. It helps regulate blood calcium levels. Normal serum value: 0. About 7 out of 10 breast cancers test positive for at least one ofAbout 7 out of 10 breast cancers test positive for at least one of these markers.

These cancers tend to have a better prognosis than cancersThese cancers tend to have a better prognosis than cancers without these receptors and are much more likely to respond towithout these receptors and are much more likely to respond to hormonal therapy such as tamoxifen or aromatase inhibitors.

Tyrosine kinase family of receptors. Its main use is as aIts main use is as a predictor of prognosispredictor of prognosis survival outlook. Those whose cancers are positive for this marker respond well toThose whose cancers are positive for this marker respond well to anthracycline based chemotherapyanthracycline based chemotherapy vs CMF and generally havevs CMF and generally have been thought to have a less favorable outlook.

ImmunoglobulinsImmunoglobulins Malignancies: blood as well as in the urine levels elevated inMalignancies: blood as well as in the urine levels elevated in multiple myeloma and Waldenstrom macroglobulinemiamultiple myeloma and Waldenstrom macroglobulinemia.. Detected by protein electrophoresis- the globulins also calledDetected by protein electrophoresis- the globulins also called monoclonal proteins or M proteins stick together and form amonoclonal proteins or M proteins stick together and form a monoclonal "spike" M spike on the readout of the test.

The level of the spike is important, because older people may showThe level of the spike is important, because older people may show low levels of a spike without havinglow levels of a spike without having myeloma ormyeloma or macroglobulinemiamacroglobulinemia..

Immunoglobulin levels are used to follow response to treatment. Lactate dehydrogenaseLactate dehydrogenase Serum LDH concentrations are elevated in 30 to 80 percent of menSerum LDH concentrations are elevated in 30 to 80 percent of men withwith pure seminomapure seminoma and in 60 percent of those withand in 60 percent of those with nonseminomatous tumors, also innonseminomatous tumors, also in lymphomaslymphomas..

In addition, a significantly elevated serum LDH has independentIn addition, a significantly elevated serum LDH has independent prognostic value in men with advanced seminoma. As a result, it is not a useful serumrecurrence in men with GCTs. As a result, it is not a useful serum marker tomarker to monitor for disease relapsemonitor for disease relapse..

Essential in patients treated for nonseminomatous germ cell tumor; very helpful in patients treated for hepatocellular carcinoma In patients treated for gestational trophoblastic disease, obtain b-hCG level once a month for 6 to 12 months. Any detectable PSA after radical prostatectomy indicates recurrence. Three consecutive PSA elevations after radiation therapy indicate recurrence.

Very helpful A testicular ultrasound. A testicular ultrasound examination revealed a soft tissue mass without a cysticexamination revealed a soft tissue mass without a cystic component. What markers will you do? All of the aboveAll of the above E. None of the aboveNone of the above LDH C. CEA D. All of the aboveD. All of the above E. None of the aboveE. None of the above Digital rectal exam.

Digital rectal exam revealed a large, nodular, and rubbery prostate glandrevealed a large, nodular, and rubbery prostate gland withwith focal hard regionsfocal hard regions. Prostatic biopsies were. Prostatic biopsies were performed. Alkaline phosphataseB. Alkaline phosphatase C. PSA D. CEA E. CA E. CA The physician notes abdominal fullness with a fluid wave,physician notes abdominal fullness with a fluid wave, consistent with ascites. He also performs a pelvicconsistent with ascites.

He also performs a pelvic examination. A cm left adnexal masscm left adnexal mass is easily felt. CA A. CA B. Applies to most patients in most circumstances but better evidence is likely to change confidence. A statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature.

A statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there is no evidence. In , an estimated 9, men will be diagnosed with testis cancer in the United States, and will die from the disease.

The incidence rate is highest among Caucasians, lowest among African-Americans, and most rapidly increasing in Hispanic populations 5,6 Age-adjusted incidence has nearly doubled over the last 4 decades for unknown reasons, from 3. Infertility is associated with the presence of GCT, though this association is thought to arise from inherent testicular dysfunction.

The increase in testis cancer incidence along with other male reproductive disorders e. The role of genetic factors is supported by the clustering of testis cancer in some families, the extreme difference in the rate of testis cancer in black and white Americans, and the finding of susceptibility loci on chromosomes 5, 6, and A multicenter case-control gene-level enrichment analysis of germline pathogenic variants in individuals with GCT relative to cancer-free controls found 22 pathogenic germline DRG variants, one-third of which were in CHEK2.

The variant CHEK2 allele was found in 9. The histological classification of post-pubertal GCT is outlined in Table 2. Compared to NSGCT, pure seminomas tend to develop at a later age, are of lower stage at diagnosis, and grow at a slower rate.

Lastly, pure seminomas are even more highly sensitive to chemotherapy relative to NSGCTs and sensitive to radiation therapy. All these differences have important treatment implications. Among NSGCT, embryonal carcinoma is the most undifferentiated cell type and has totipotential capacity to differentiate into other NSGCT cell types yolk sac, choriocarcinoma, and teratoma within the primary tumor and at metastatic sites. Among NSGCT patients, the potential for teratoma to arise within the primary tumor or at metastatic sites has important management implications.

Though histologically benign, teratomas contain many genetic abnormalities frequently found in malignant GCT elements. However, their underlying genetic instability may lead to uncontrollable growth and invasion of surrounding structures growing teratoma syndrome 24 or transformation into somatic-type malignancies such as sarcoma or adenocarcinoma.

Testis cancer is one of the few malignancies with reliable serum tumor markers alpha-fetoprotein [AFP], human chorionic gonadotropin [hCG], and lactate dehydrogenase [LDH] that are essential for diagnosis, prognosis, clinical staging, management, response to therapy, and post-treatment surveillance.

The half-life of AFP is five to seven days. Other malignant sources of AFP include cancers of the stomach, pancreas, biliary tract, liver, and lung. Non-malignant sources of AFP include liver disease infectious, drug-induced, alcohol-induced, autoimmune , ataxia telangiectasia, hereditary tyrosinemia, and heterophile antibodies.

The half-life of hCG is hours. The alpha-subunit of hCG is common to several pituitary tumors, thus immunoassays for hCG are directed at the beta-subunit. Similarly, heterophile antibodies, hypogonadism, and possibly some medications can lead to false-positive elevations of hCG.

The magnitude of LDH elevation correlates with bulk of disease. As a non-specific marker, its main GCT use is in the prognostic assessment at diagnosis. Prognosis and initial management decisions are dictated by clinical stage, which is based on the pathological stage of the primary tumor, post-orchiectomy serum tumor marker levels, and staging as determined by physical examination and imaging.

The cancer is only in the seminiferous tubules small tubes inside each testicle. It has not grown into other parts of the testicle pTis. It hasn't spread to nearby lymph nodes N0 or to distant parts of the body M0. All tumor marker levels are within normal limits S0. The tumor has grown beyond the seminiferous tubules, and might have grown outside the testicle and into nearby structures pT1-pT4. The cancer has not spread to nearby lymph nodes N0 or to distant parts of the body M0.

The tumor has grown beyond the seminiferous tubules, but is still within the testicle, and it hasn't grown into nearby blood vessels or lymph nodes pT1. The cancer hasn't spread to nearby lymph nodes N0 or to distant parts of the body M0. The tumor has grown outside of the testicle and into nearby structures pT2-pT4. At least one tumor marker level is higher than normal S1-S3. The cancer has spread to 1 or more nearby lymph nodes N1-N3 , but it hasn't spread to distant parts of the body M0.

The cancer has spread to at least 1 nearby lymph node but no more than 5, if checked by surgery , and none of the lymph nodes are larger than 2 centimeters cm across N1. The cancer has not spread to distant parts of the body M0. All tumor marker levels are within normal limits S0 , or at least 1 tumor marker level is slightly higher than normal S1. The cancer has spread to at least 1 nearby lymph node that's larger than 2 cm but no larger than 5 cm, OR it has grown outside of a lymph node, OR more than 5 nodes contain cancer found during surgery N2.

The cancer has spread to at least 1 nearby lymph node that's larger than 5 cm across N3. The cancer might or might not have spread to nearby lymph nodes any N. It has spread to distant parts of the body M1. It has spread to distant lymph nodes or to the lungs M1a.

At least 1 tumor marker level is much higher than normal S2. At least 1 tumor marker level is very high S3. It has spread to distant parts of the body other than the lymph nodes or to the lungs M1b.

Tumor marker levels might or might not be higher than normal any S. As GCT patients are often healthy and young with long estimated life expectancy, reducing the burden of therapy and treatment-related toxicity are particularly important. Testis cancer is the most common solid malignancy among men aged years. Acute testicular pain is less common and caused by rapid expansion of the testis due to intra-tumor hemorrhage or infarction caused by rapid tumor growth.

A solid testis mass may be distinguished from other disease entities by physical examination and ultrasound. Diagnostic delay is a common phenomenon, with both patients and physicians contributing to this delay, 37,38 and often leads to unnecessary intensification of therapy and potential compromise in cure rate.

Serum AFP, hCG, and LDH are essential for characterization and risk stratification and should be obtained in any patient suspected of having testis cancer.

For patients with persistently elevated post-orchiectomy serum tumor markers, it is essential to know whether these levels are declining by their respective half-lives or not, or whether they are rising, as this impacts subsequent treatment decisions. Impaired spermatogenesis is associated with GCT and both are thought to arise from inherent testicular dysfunction. Irradiation doses exceeding 6 Gy may result in permanent azoospermia. In patients with an absent or abnormal contralateral testis or in those with known subfertility, sperm banking may be offered prior to orchiectomy.

For patients receiving chemotherapy, the rates of hypogonadism are directly associated with the number of cycles. Ultrasound is widely available, inexpensive, non-invasive, and has excellent performance characteristics for the diagnosis of testicular cancer. Testicular microlithiasis in the absence of solid mass and risk factors for developing a germ cell tumor does not confer an increased risk of malignant neoplasm and does not require further evaluation.

Additional metadata of men with testicular microlithiasis indicates the risk of testicular GCT is only increased in men with an additional risk factor i. Men with risk factors and testicular microlithiasis should be counseled about the potential increased risk of GCT, perform periodic self-examination, and be followed by a medical professional.

Management options include observation with serial physical examination and ultrasound, inguinal orchiectomy, and TSS through an inguinal incision with intraoperative frozen-section. Patient preference and shared decision-making should be employed in choosing a management strategy. Antibiotics are inappropriate unless signs and symptoms of epididymo-orchitis i. A systematic review identified nine studies evaluating MRI in the diagnosis of masses suspected to be testicular GCT. MRI is often dependent on expert radiology interpretation, and referral to an experienced MRI center is recommended when possible.

Radical orchiectomy establishes a diagnosis and primary T stage while being curative for the majority of men with clinical stage I testicular GCT. Patients may electively choose to have a testicular prosthesis at the time of orchiectomy. Testicular prosthesis is associated with a very low risk of morbidity primarily infection , malposition, deflation, or need for explant. Patients may choose to have a delayed prosthesis implantation if it was not offered prior to orchiectomy.

Transscrotal orchiectomy and transscrotal biopsy are not recommended if malignancy is suspected. For patients who experience scrotal violation during surgery, biopsy of a testicular mass through the scrotum, or scrotal exploration leading to an incidental diagnosis of testicular cancer, the rates of local recurrence are significantly higher than for patients undergoing radical inguinal orchiectomy.

In a systematic review, 2. Notably, there was no difference in rates of metastatic disease or all-cause mortality based on scrotal violation. Guideline Statement 11c: When TSS is performed, in addition to the suspicious mass, multiple biopsies of the ipsilateral testicle normal parenchyma should be obtained for evaluation by an experienced genitourinary pathologist. TSS or partial orchiectomy can be considered in men with a high-likelihood of harboring a benign testicular tumor or in men with an anatomically or functionally solitary testicle who desire to preserve hormone and fertility function.

Utilizing a pathologist experienced in the histologic assessment of GCT is recommended. Specifically, the decision regarding whether the testicle should be removed in its entirety if the diagnosis of a testicular cancer is made or cannot be determined on frozen section should be determined prior to surgery. TSS is an option for preservation of hormonal function and fertility in patients with congenital, acquired, or functionally solitary testis or bilateral synchronous malignancy. Due to these high rates of local relapse, close monitoring with physical examination and ultrasound of the testis are imperative.

Complications after TSS include testicular atrophy in 2. Little data exist regarding the long-term rate for preservation of fertility in this population. The presence of GCNIS informs the likelihood and timing of recurrence and may assist patients and providers about the need for and timing of adjuvant radiotherapy. The presence of GCNIS should prompt a discussion with the patient regarding close surveillance or adjuvant therapy. While the absence of GCNIS is reassuring, it is highly likely that GCNIS is present outside of the sampled tissue, and the patient should be followed with serial self-testicular exam, ultrasound, and tumor markers as appropriate.

Guideline Statement 13b: Clinicians should recommend surveillance in patients with GCNIS or malignant neoplasm after TSS who prioritize preservation of fertility and testicular androgen production. Guideline Statement 13c: Clinicians should recommend testicular radiation Gy or orchiectomy in patients with GCNIS or malignant neoplasm after TSS who prioritize reduction of cancer risk taking into consideration that radiation reduces the risk of hypogonadism compared to orchiectomy.

Chemotherapy is not recommended. Clinicians should engage in shared decision-making discussing the risks and benefits with specific attention to the oncologic efficacy, impact on fertility, and hormonal function associated with each option.

Sperm banking and treatment of hypogonadism should be discussed with the patient and appropriately implemented as needed. Expectant management with deferred radiation or orchiectomy may be considered in the patient who desires future paternity without the need for assisted reproductive techniques. Close monitoring in these patients and compliance with follow-up is essential. The rationale for radiation therapy is to lower the likelihood of developing cancer while attempting to preserve Leydig cell function and testosterone production.

In the largest study of men with GCNIS in the setting of a contralateral testicular cancer treated with Gy, 3 participants 2. Orchiectomy eliminates the risk of developing testicular cancer but can be unnecessary for those unlikely to develop cancer and lead to lower rates of fertility and testosterone levels. In patients prioritizing preservation of fertility and testicular androgen production after a diagnosis of GCNIS or malignant neoplasm after TSS, surveillance should be recommended as radiation therapy, surgery, and chemotherapy can result in infertility and hypogonadism.

However, the reduced risk of hypogonadism associated with a lower radiation dose is not firmly established. Another study comparing 14 to 20 Gy showed a stable testosterone decrease 3.

Radiation reduces rates of a second GCT or persistence of GCNIS, eliminates fertility, and is associated with higher rates of hypogonadism compared to surveillance. A clinician should treat the affected testicle with up to Gy of radiation therapy. Radical orchiectomy eliminates the risk of GCNIS or malignant neoplasm and is considered the most definitive treatment, but this procedure is associated with higher rates of infertility and hypogonadism.

Use of pre-orchiectomy markers for staging and risk stratification can lead to over- or under-treatment with resulting excess rates of toxicity or relapse, respectively. Elevated post-orchiectomy serum tumor markers generally indicate systemic disease and the need for subsequent treatment. However, in the absence of obvious metastatic disease requiring chemotherapy, serum tumor markers should be serially measured following orchiectomy to ascertain rise or persistent elevation prior to consideration of subsequent therapy.

In patients with declining serum tumor markers post-orchiectomy, staging and treatment decisions are made after adequate time has elapsed to allow for markers to normalize according to their half-life hCG: hours; AFP: days. When chemotherapy is indicated for newly diagnosed advanced testicular GCT, selection of the appropriate regimen bleomycin, etoposide, cisplatin [BEP]; etoposide, cisplatin [EP]; etoposide phosphate, ifosfamide, cisplatin and number of cycles 3 versus 4 is based on the IGCCCG prognostic model.

In general, patients with good-risk disease are treated with either three cycles of BEP or four cycles of EP, and those with intermediate- or poor-risk disease are treated with four cycles of BEP or etoposide phosphate, ifosfamide, cisplatin.

Recent data suggest inferior outcomes when these patients are treated according to pediatric guidelines for metastatic disease. Failure to consider potential etiologies of false-positive marker elevation can lead to treatment in the absence of disease and subjecting the patient to unnecessary acute and long-term toxicities.

When low-level elevation of either marker is present, particularly in the absence of metastatic disease on imaging, clinicians should consider one of these alternative etiologies. With elevated AFP or hCG due to metastatic GCT, a consistent marker rise is typically seen, whereas in false-positive etiologies, the marker level is often stable or fluctuates. The retroperitoneal lymph nodes are the most frequent site of initial metastatic dissemination for both seminoma and NSGCT.

Less frequently, metastasis can be found within the retained spermatic cord or involving pelvic lymph nodes the latter are uncommon in the absence of retroperitoneal lymphadenopathy. As such, imaging of the retroperitoneum and pelvis at diagnosis is paramount for staging and treatment selection. In general, the smaller the size definition of a positive node, the greater the sensitivity and lesser the specificity. CT scans should be performed with IV contrast, if possible, for better tissue differentiation and should be performed in a single phase according to ALARA principles of minimizing ionizing radiation.

Guideline Statement 19c: In patients with clinical stage I seminoma, clinicians should preferentially obtain a chest x-ray over a CT scan. Guideline Statement 19d: In patients with NSGCT, clinicians may preferentially obtain a CT scan of the chest over a chest x-ray and should prioritize CT chest for those patients recommended to receive adjuvant therapy.

The thorax is the most common site of metastatic disease after retroperitoneal lymph nodes for men with GCT; lung metastases represent the most common site of visceral metastases.

A retrospective analysis of low-stage seminoma patients evaluated by CT chest imaging found a high rate of false-positive chest findings in those with normal CT abdomen-pelvis imaging. Optimal management for patients with testis cancer is often enhanced following a multi-disciplinary discussion. When possible, this includes a collaborative discussion including urology, medical oncology, and, for patients with stage I-II seminoma, radiation oncology.

Application of a multi-disciplinary disease management team has been demonstrated to significantly decrease the rates of overtreatment, decrease relapse, and improve survival.

The evaluation of testicular cancers is challenging due to heterogeneity of tumor and multiple histology elements often present in NSGCT. For example, a patient with elevated and rising post-orchiectomy levels of AFP with or without clinical evidence of metastases may be appropriately managed as metastatic NSGCT and initiate chemotherapy before expert pathological review of the orchiectomy specimen.

Many patients with newly diagnosed GCT have equivocal imaging findings, not clearly consistent with localized or metastatic disease. Most often, this manifests as the presence of borderline enlargement 0. In the absence of elevated tumor markers, these findings should be approached cautiously rather than hastily initiating treatment for metastatic disease. Repeating imaging six to eight weeks after the initial CT can be helpful in establishing the probable etiology.

Enlarging lymph nodes are often associated with metastatic disease, while stable or regressing lymph nodes suggest benign etiologies. For stage I seminoma, patients are candidates for surveillance, adjuvant carboplatin, or adjuvant radiation therapy after orchiectomy. Adjuvant carboplatin and radiation reduce the risk of relapse but do not improve cancer-specific survival compared to surveillance.

There is lack of agreement and validation of risk factors for recurrence. The use of tumor size and rete testis involvement is not recommended in determining management of stage I seminoma. Oncologic outcomes after diagnosis of stage I seminoma are favorable regardless of initial management strategy. Comparative analyses are limited and retrospective but show no apparent survival differences. Studies of stage IIB seminoma suggest fewer relapses after chemotherapy compared to radiation therapy.

Long-term toxicity of therapy can involve the cardiovascular, gastrointestinal, and hematologic systems and may cause infertility and can rarely result in secondary malignancy. The benefit of surveillance is greatest for men with a lower risk of relapse. Some men may prefer active treatment with RPLND or one cycle of BEP chemotherapy in order to reduce the risk of relapse and the need for more extensive treatment should a relapse occur on surveillance.

Men with prior inguinal surgery, for example, may have altered lymphatic drainage and thus are not ideal candidates for RPLND.

Patients with compromised renal function are at increased risk of complications from BEP chemotherapy. Decision-making should take into account all these factors. Teratoma has the capacity to dedifferentiate into somatic malignancies including sarcomas and carcinomas that are less responsive to chemotherapy than GCT. These tumors are rare, and the literature is limited to relatively small case series. A series of 10 patients with metastatic teratoma with somatic—type malignancy from Memorial Sloan Kettering Cancer Center reported that seven died with systemic therapy.

Given the insensitivity of these tumors to chemotherapy, RPLND is recommended for these patients to remove any retroperitoneal metastases that may exist and reduce the risk of relapse.

However, it is important to distinguish transformed GCT from teratomas: the presence of teratoma in the primary tumor is not a specific indication for RPLND, but the rationale for RPLND is stronger when teratoma is present because of concerns about chemotherapy resistance and late recurrence. The benefits of RPLND for these patients include reduced exposure to chemotherapy, removal of any chemotherapy-resistant teratoma, and a reduced need for serial retroperitoneal imaging.

Certain factors can help guide decision-making. When the primary testis tumor contains teratoma, the rationale for RPLND is stronger due to the chemotherapy resistance of this tumor type. Patients who have had inguinal surgery prior to orchiectomy may have altered lymphatic drainage and chemotherapy is generally preferred. Similarly, in a multicenter study of adjuvant chemotherapy for pathological stage II disease, over half of men with pN2 disease relapsed if they did not receive adjuvant chemotherapy.

For patients with a predominance of teratoma in their primary tumor and patients with a relative contraindication to chemotherapy, RPLND is an effective alternative.

RPLND is a technically complex surgery encompassing removal of retroperitoneal lymph nodes while preserving the great vessels, surrounding organs, and ejaculatory nerves. For patients with metastatic disease, treatment at a higher-volume hospital is independently associated with superior overall survival. Minimally-invasive RPLND can be considered with an experienced surgeon who has a thorough understanding of testicular cancer and the capability to convert to open surgery, if needed.

A full, bilateral template includes removal of the para-aortic, retro-aortic, pre-aortic, left common iliac, interoartocaval, pre-caval, para-caval, retro-caval, and right common iliac lymph nodes in addition to the ipsilateral gondal vessels. A full, bilateral template dissection should be performed in patients with suspicious lymph nodes based on CT imaging or intraoperative evaluation and in those with somatic-type malignancy teratoma with malignant transformation in the primary tumor.

This template is associated with the lowest rates of retroperitoneal recurrence. In patients with clinically negative lymph nodes, a full, bilateral template or a modified template dissection may be performed. The extent of the dissection for modified templates varies greatly among published series. Modified templates are associated with inferior ejaculatory rates compared to nerve-sparing techniques.

There was not consensus among panel members whether omission of para-aortic lymph nodes above the inferior mesenteric artery from the template is acceptable. There was not consensus whether the interaortocaval lymph nodes may be safely omitted when performing a left modified template dissection. Among men having a primary RPLND, options for adjuvant treatment versus surveillance are based on pathologic findings from the surgery.

A randomized trial of adjuvant chemotherapy versus observation for pathological stage II disease after primary RPLND showed significant reduction in relapse but no difference in overall survival. Accordingly, it remains a central tenant for close monitoring to identify relapses in a timely manner. Adherence to a prescribed regimen of surveillance with office visits, imaging, and laboratory testing when indicated is important to optimize detection and minimize treatment burden and morbidity.

There are no randomized trials comparing follow-up schedules for physical examinations and tumor markers for surveillance in stage I seminoma. Therefore, consideration for routine assessment with hCG can be limited to only those with elevated hCG prior to orchiectomy; reserving full panel serum tumor marker assessment as clinically indicated in the remaining patients for concerns of new onset symptoms or radiographic changes suggestive of relapse.

Therefore, the first 36 months remains the period of the most intensive assessment. The role for routine imaging of the chest and pelvis remains uncertain. Because isolated chest relapses are rare, chest imaging should be reserved for patients identified with elevated serum tumor markers or radiographic evidence of disease in the RP.

Routine imaging of the pelvis is also associated with a low yield for identifying isolated relapses in the absence of retroperitoneal disease and can be omitted; such imaging may be obtained when signs of relapse are evident. Based on the higher recurrence rates and earlier recurrences in patients with lymphovascular invasion, a follow-up interval at the more intensive end of the ranges provided is recommended.

While relapses after two years are uncommon, they are more likely in patients without lymphovascular invasion. Clinical stage I seminoma and NSGCT patients with evidence of relapse on surveillance should undergo repeat staging imaging studies as for newly-diagnosed GCT, including physical examination including the contralateral testis , chest-abdominal-pelvic imaging, and serum tumor marker AFP, hCG, LDH determinations.

Patients should be assigned a new TNM-S clinical stage according to the results of these repeat staging investigations, and they should be treated according to the clinical stage assignment at the time of relapse. In rare instances, evidence of relapse may arise from a de novo metachronous contralateral primary tumor. One would be the stability of this complicated engineering platform when constantly applied in a diagnostic mode.

Another would be the lot-to-lot reproducibility of the chip surface chemistry to assure the validity of comparative observations in complex clinical material such as serum, plasma, and urine. In addition, different underlying disease conditions in control and disease populations used for discovery or diagnosis might generate erroneous results. Finally, it cannot be assumed that current SELDI-TOF technology is ready for routine clinical diagnostic applications in the clinical chemistry laboratory.

The technology should provide direction for the searching process, to identify and isolate disease- specific serum biomarkers that may be combined to improve detection, diagnosis, and prognosis of urologic cancers. Future engineering and software improvements to refine potential clinical laboratory applications are anxiously awaited by the medical community. In order to identify the presence of low-abundance, differentially expressed proteins that may become masked within a sample, sample preprocessing and a more diverse array of capture surfaces will be required.

The development of highly stable engineering platforms, more novel surface chemistry enhancements, improved manufacturing methods to maintain the reproducibility of mass-produced chips, and enhanced sample preparation techniques will enable the expanded detection of more cancer biomarkers in various disease states and the potential for new diagnostic instrument applications.

Current developments such as SELDI-TOF enable the rapid analysis of small, crude samples from a variety of biological materials for biomarker detection and identification, and for the study of biomolecular interactions. Continued application of this technology to the research problems that remain for prostate, bladder, and renal cell cancer will result in the identification of unique proteins and protein profiles that characterize cancer progression from a healthy state to more aggressive malignant states.

Further identification and characterization of these proteins should enable investigators to develop novel diagnostic and therapeutic modalities for cancer research. During the last two decades, biomarker research has progressed with the introduction of new proteomic analytical techniques. Previously, the use of two-dimensional electrophoresis dominated this field and provided numerous urologic candidate biomarker discoveries. Continued application of SELDI-TOF to research problems for prostate, bladder, and renal cell cancer will aid in the discovery of unique protein profiles that characterize the progression of cancer from healthy to more aggressive malignant states.

National Center for Biotechnology Information , U. Journal List Rev Urol v. Rev Urol. Author information Copyright and License information Disclaimer. The laboratory of Daniel W. Abstract During the last two decades, biomarker research has benefited from the introduction of new proteomic analytical techniques. Techniques in Proteomic Analysis To date, the combination of two-dimensional 2-D gel electrophoresis and mass spectroscopy MS has been the effective traditional technique for analyzing the protein complement of cells and tissues.

Open in a separate window. Figure 1. Figure 2. Data Analysis The task of interpreting the data produced by proteomic technologies represents an emerging field known as bioinformatics. Applications of SELDI in Urology The diversity of SELDI is appreciated because of its ability to detect potential biomarkers from crude samples such as serum, cellular extracts both from microdissected cells and cell culture , seminal plasma, and urine.

Figure 3. Figure 4. Figure 5. Figure 6. Limitations of SELDI There are some limitations to consider with the application of this technology to the biomarker discovery process as well as its potential use as a diagnostic instrument. Main Points During the last two decades, biomarker research has progressed with the introduction of new proteomic analytical techniques.

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