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Current Role of Retroperitoneal Lymph Node Dissection in Testicular CancerPublished on Diagnostic Imaging (http://www.diagnosticimaging.com)

Current Role of Retroperitoneal Lymph Node Dissection inTesticular CancerReview Article [1] | May 01, 1997By Graeme S. Steele, MBBCh [2] and Jerome P. Richie, MD [3]

Carcinoma of the testis is the most common malignancy in males 15 to 35 years of age. Testicularcancer has become one of the most curable solid neoplasms and, as such, serves as a paradigm forthe multimodality treatment of malignancies. The cure rate for patients with clinical stage I diseaseis nearly 100%, and patients with advanced disease now achieve complete remission rates of over90%. The markedly improved outlook for patients with this cancer over the past 15 years has led toa reassessment of management options, especially in patients with clinical stage I disease. Therealization that platinum-based chemotherapy could cure most patients with an advancednonseminomatous germ cell tumor (NSGCT), especially those with minimal disease, led to theintroduction of various strategies to decrease the morbidity associated with surgical management.These strategies include surveillance protocols, chemotherapy for clinical stage II disease, andobservation protocols for a subset of patients with advanced disease who have had a partialresponse to chemotherapy. Retroperitoneal lymph node dissection (RPLND) has an important placein the management of both low- and high-stage testicular cancer. It offers the patient two basicbenefits: accurate staging and the possibility of a surgical cure, even in the presence of metastaticdisease. [ONCOLOGY 11(5):717-729, 1997]

ABSTRACT: Carcinoma of the testis is the most common malignancy in males 15 to 35years of age. Testicular cancer has become one of the most curable solid neoplasms and,as such, serves as a paradigm for the multimodality treatment of malignancies. The curerate for patients with clinical stage I disease is nearly 100%, and patients with advanceddisease now achieve complete remission rates of over 90%. The markedly improvedoutlook for patients with this cancer over the past 15 years has led to a reassessment ofmanagement options, especially in patients with clinical stage I disease. The realizationthat platinum-based chemotherapy could cure most patients with an advancednonseminomatous germ cell tumor (NSGCT), especially those with minimal disease, led tothe introduction of various strategies to decrease the morbidity associated with surgicalmanagement. These strategies include surveillance protocols, chemotherapy for clinicalstage II disease, and observation protocols for a subset of patients with advanceddisease who have had a partial response to chemotherapy. Retroperitoneal lymph nodedissection (RPLND) has an important place in the management of both low- andhigh-stage testicular cancer. It offers the patient two basic benefits: accurate stagingand the possibility of a surgical cure, even in the presence of metastatic disease.[ONCOLOGY 11(5):717-729, 1997]

Introduction

Despite the fact that carcinoma of the testis accounts for only 1% of all malignancies in males, it isthe most common solid malignancy affecting males between the ages of 15 and 35 years. As such,testicular cancer raises significant issues pertaining to such factors as future fertility and thedevelopment of a potentially life-threatening disease in a previously healthy, productive individual.These issues need to be taken into account in overall patient management.The incidence of testicular cancer has gradually increased over the last 25 years, from 2.3 cases per100,000 men in 1964 to 4 per 100,000 men in 1993; this trend is due mainly to an increasedincidence in white males.[1,2] Thirty years ago, testicular cancer accounted for 11.4% of all cancerdeaths in the 25- to 34-year-old age group, with an overall 5-year survival rate of 64%.[3] In 1994,the cure rate for testis cancer approached 100%. Improved diagnostic techniques and tumormarkers, as well as effective platinum-based multidrug chemotherapeutic regimens, have combinedto significantly reduce patient morbidity and mortality.In addition, modifications in the surgical management of testicular cancer have significantly lowered

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the morbidity associated with the classic full bilateral retroperitoneal lymph node dissection (RPLND),which was routinely performed prior to the early part of the 1980s. This advance, combined with thefact that approximately 30% to 50% of patients with a clinical stage I nonseminomatous germ celltesticular tumor (NSGCT) actually have pathologic stage II disease, has made surgery an importanttreatment option for both physicians and patients.Retroperitoneal lymph node dissection not only is an important component of the management ofpatients with low-stage NSGCT but also has a major role in the management of residual diseasefollowing chemotherapy. Approximately 30% of patients who are initially treated with chemotherapyare found to have a residual mass at follow-up. Removing this mass restages the patient and, incases where persistent carcinoma exists, the physician is alerted to the need for furthermanagement.Therefore, as will be discussed below, RPLND plays a role in both low- and high-stage disease. It is awell-defined, reproducible surgical procedure with low morbidity, which benefits the patient in termsof both allowing for accurate pathologic staging and providing a surgical cure.

Natural History of Testicular Cancer

Clinical observation of patients with testicular cancer has led to an understanding of its local growthcharacteristics, as well as its patterns of spread. Following malignant transformation of the germinalepithelium, tumor growth initially tends to remain confined to the testis itself, as the tough fibroustunica albuginea offers a degree of protection to the epididymis. The tumor gains access to thelymphatics at the testicular mediastinum. FIGURE 1

Lymphatic Drainage

With the notable exception of choriocarcinoma, germ cell testicular neoplasms spread in apredictable, stepwise fashion. The lymphatic drainage of the testicle has been well documented byboth surgeons and anatomists.[4-6] One of the first experimental studies of testicular lymphaticswas performed in 1910 by Jamieson and Dobson (Figure 1).[7] Apart from their importantcontribution in defining lymphatic drainage of the testicle, these authors correctly pointed out that inorder to cure testicular cancer, complete removal of the "retroperitoneal lymphatic area" wasnecessary; however, they felt that this procedure was exceedingly difficult and dangerous, if notimpossible! FIGURE 2

Nodal Metastases

The spermatic cord contains four to eight lymphatic channels that ascend into the retroperitoneumand fan out medially into the retroperitoneal lymph node chain. The first echelon of lymph nodesdraining the right testis is located within the interaortocaval nodes, at the level of the secondvertebral body. The first echelon of nodes draining the left testis is located in the para-aortic region

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in an area bounded by the renal vein superiorly, the aorta medially, the ureter laterally, and theorigin of the inferior mesenteric artery inferiorly. Following spread of germ cell neoplasms to eitherthe left or right primary echelon of nodes, subsequent metastasis may occur in a retrograde fashionto the common external and inguinal nodes, or cephalad via the cysterna chyli, thoracic duct, andsupraclavicular nodes (Figure 2).In a review of 104 consecutive patients with stage II (B) NSGCT, Donohue et al[8] made a number ofimportant observations confirming the predictable lymphatic spread of testicular tumors. Theyreported that suprahilar lymph node spread was extremely rare in stage BI disease but was notuncommon in stage BII disease. They also confirmed the absence of contralateral node involvementin low-stage disease when the ipsilateral nodes were negative.[9] In addition, in this series gonadalvein involvement was noted in a significant number of cases in both low- and high-stage B disease.Obviously, these observations have important implications for the surgical management of testicularcancer.Despite the predictability of lymph node metastasis in testicular cancer, there is a 5% distant failurerate following node-negative RPLND.[10] This is probably due to the fact that the testicularlymphatics may very occasionally bypass the retroperitoneal lymph nodes altogether andcommunicate directly with the thoracic duct. Lymphatics of the epididymis drain into the externaliliac chain; therefore, in locally extensive disease, epididymal involvement may be associated withpositive pelvic lymph nodes. Testicular cancer that involves the scrotum may result in inguinal nodemetastasis; in addition, prior scrotal surgery or retrograde spread from extensive retroperitonealinvolvement may also cause inguinal node metastasis.Scrotal violation in the setting of orchiectomy for testicular cancer has generally been condemned ascompromising patient prognosis. As a result, inguinal orchiectomy with high ligation of the cord hasbeen the standard of care in the initial management of testicular cancer for almost 100 years.[11]However, Capelouto et al[12] recently conducted a meta-analysis focusing on the implications ofscrotal violation in patients with testicular cancer. Out of a total of 1,182 patients, scrotal violationhad occurred in 206 patients. No statistical differences in distant recurrence or survival were found,implying that scrotal violation may not carry a significantly worse prognosis.In summary, apart from choriocarcinoma, which undergoes both lymphatic and hematogenousspread at an early stage, germ cell testicular tumors tend to spread, in a predictable fashion, to theretroperitoneal lymph nodes. Suprahilar involvement usually develops only in higher-stage diseaseand, as such, occurs more frequently on the left side than on the right. If the ipsilateral nodes arenegative, the contralateral nodes also are uninvolved. Cross-metastases occur more frequently withright-sided tumors.Distant spread of testicular cancer occurs most commonly to the pulmonary region, withintraparenchymal pulmonary involvement. Subsequent spread is to the liver, viscera, brain, and, latein the disease course, bone.[13]This predictable pattern of spread has led to the development of new surgical techniques thatprovide both accurate pathologic staging and therapeutic benefit, while at the same time beingassociated with minimal morbidity.

Prediction of Metastatic Potential

Most patients with NSGCT present with clinical stage I disease. Since 30% to 50% of these patientsmay have clinically undetectable metastases, controversy exists as to their subsequentmanagement.[14,15] In order to offer the patient the highest chance of cure with the lowest possiblemorbidity, certain parameters are used to predict the likelihood of metastasis.[16] Factors thatdetermine the likelihood of relapse in the retroperitoneal nodes, or of late recurrence in clinical stageI NSGCT, are: the extent of the primary tumor (ie, T-stage), lymphatic or vascular invasion, thepresence of embryonal carcinoma in the primary tumor, and the absence of yolk sac tumor.[17]Prognostic indices using these risk factors have been developed. As a result of these indices,patients with clinical stage I NSGCT are no longer managed as a homogeneous group. Rather,treatment may now be individualized according to the likelihood of positive retroperitoneal lymphnodes. Patients who are at low risk of having positive nodes may be placed into observationprotocols and thus spared the morbidity of adjuvant therapy. However, despite the prognosticcriteria, it is still not possible to establish highly accurate distinctions between patients who shouldand should not receive adjuvant therapy. In this regard, the Medical Research Council study in theUnited Kingdom[18] showed that the high- risk group constituted fewer than 25% of patients withtesticular cancer and accounted for less than half of the relapses.

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Staging of Testicular Cancer

TABLE 1

Clinical Staging Systems for Testicular Cancer

Both clinical and pathologic staging systems for NSGCT have been developed (Table 1 and Table 2).Since therapies differ for seminoma and NSGCT, there are separate staging systems for these twoentities. Although numerous staging systems are currently employed, the majority are a variation onthe system proposed by Boden and Gibb in 1951.[19] It is important to note that the measurementof the size of involved lymph nodes in the Memorial Sloan-Kettering Cancer Center system refers tothe total diameter of all enlarged lymph nodes, not to the diameter of the largest lymph node.Low-stage disease includes stages I (A) and IIA (B1) disease, whereas high-stage diseaseencompasses stages IIB (B2), IIC (B3), and III (C) disease. This distinction between low- andhigh-stage disease is important, as it determines, to a large degree, what type of adjuvant therapythe patient receives and also is used to evaluate the results of various treatment protocols. TABLE 2

Pathologic Staging Systems for Testicular Cancer

The clinical staging systems are based on noninvasive diagnostic techniques, whereas pathologicstaging is based on the specimens obtained at radical orchiectomy and RPLND (Table 2). The stagingerror which is associated with clinical staging is therefore removed.

Staging Work-up

Following radical orchiectomy and evaluation of the primary tumor, the staging work-up formetastatic disease commences. The primary landing sites for metastatic disease in theretroperitoneum have been well described (Figure 2). Prior to the development of CT, theretroperitoneum was assessed by a combination of physical examination, intravenous pyelography,and bipedal lymphangiography. Due to the low yield and potential morbidity oflymphangiography,[20] this technique has been abandoned in the work-up of NSGCT.Computed tomographic scanning is currently the imaging modality of choice for the retroperitoneumin patients with germ cell testicular tumors. Since the CT scan cannot detect the presence ofmicrometastases, it is associated with a significant false-negative rate: 44% in a study by Richie etal[21] and 59% in a report by MacLeod et al.[22] In general, the accuracy of CT scanning of theretroperitoneum is 68% to 90%.[23-25]Improved diagnoses with newer generations of scanners and techniques have not led to a significantdecrease in false-negative rates. Therefore RPLND remains the gold standard for staging patientswith NSGCT and, as such, has the advantage of detecting micrometastases in patients who wouldotherwise have been placed on an observation protocol (which would be destined to fail). In addition,it provides a surgical cure in a significant subset of patients.

Fertility in Patients With Testicular Cancer

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Fertility is one of the most important issues in patients with NSGCT. In this regard, it needs to beborne in mind that the preservation of ejaculation is not synonymous with achieving pregnancy.[26]In fact, approximately 40% to 70% of patients are hypofertile, at least temporarily, after orchiectomyfor testicular cancer.[27] This may be due to a variety of factors, such as the association ofcryptorchidism with testicular cancer, stress, and the surgical trauma to one testicle, which mayhave an effect on the contralateral testicle.[28] In addition, higher concentrations of antispermantibodies are present in patients with testicular cancer than in the normal population.[29] In asignificant percentage of these patients, semen analyses will improve after therapy. Nevertheless,an estimated 25% of patients will have a persistent subfertile pattern on semen analysis.[30] Thus,only 75% of patients with NSGCT have fertility that can be preserved.The best measurement of fertility is pregnancy. A retrospective review of the Indiana Universityexperience in 201 patients with clinical stage I disease NSGCT showed that, of 66 patients whoattempted to achieve a pregnancy after RPLND, 50 (76%) were successful.[31] Also, Mansen et alhave studied paternity in patients treated with chemotherapy for testicular cancer.[32] In this study,three of eight patients who attempted pregnancy after platinum-based chemotherapy weresuccessful.

Retroperitoneal Lymph Node Dissection

RPLND has evolved considerably since the early 1900s when the technique was first performed.Bilateral dissections, which became standard therapy for low-stage testicular cancer in the 1950sand '60s, gave way, in the 1980s and '90s, to less extensive, template and nerve-sparing techniques.Currently, the type of dissection performed varies, depending on which disease stage is beingtreated.RPLND-I--This dissection is performed in patients with no clinical signs of spread to theretroperitoneum and no surgically visible disease, ie, clinical stage I disease. The surgical techniqueemployed is either the template or nerve-sparing technique. In the modified template technique, thedissection is complete above the level of the inferior mesenteric artery but is limited to the ipsilateralside below the level of the inferior mesenteric. In the nerve-sparing RPLND, the lumbar sympatheticnerves are prospectively identified and preserved, and the node-bearing tissues around these nervesare then removed. Both techniques preserve ejaculation in the vast majority of patients.RPLND-II--This is performed in patients with low-volume, clinically demonstrable disease or withvisible disease at surgery, ie, clinical stage IIA or IIB disease. The surgical boundaries are generallywider than in RPLND-I, are usually bilateral above the inferior mesenteric artery, and, in most cases,are bilateral below the inferior mesenteric artery as well. The lumbar sympathetic nerves and thehypogastric plexus are carefully preserved, resulting in preservation of ejaculation in over 95% ofpatients when the procedure is done by experienced surgeons.RPLND-III--This is a cytoreductive procedure performed after chemotherapy. Only in highly selectedcases are nerve-sparing boundaries utilized. Up to 30% to 50% of patients may have preservation ofejaculation following this procedure.

Management of Clinical Stage I Disease

RPLND-I vs Surveillance

The decision to place a patient on a surveillance protocol or to perform RPLND depends on a numberof factors, such as T-stage, tumor histology, presence of vascular or lymphatic invasion, andpatience compliance. Local expertise in performing RPLND is also an important factor.There are a number of fundamental reasons for advocating RPLND in clinical stage I disease:Approximately 30% of patients who present with clinical stage I NSGCT actually have pathologicstage II tumors. By performing RPLND in this subset of patients, their more extensive disease will berecognized earlier in the disease course. Testicular cancer is no exception to the general rule thatwhen a cancer is discovered early, not only is treatment better tolerated and less severe but also thechance for cure is that much greater.Accurate pathologic staging allows for earlier definition of treatment requirements. For example,patients found to have pathologic stage II disease can be given the option of two courses ofchemotherapy.[33] If, on the other hand, these patients are placed on a surveillance protocol andsuffer a subsequent clinical recurrence, three to four courses of chemotherapy would be required,with attendant increases in short- and long-term morbidity.Retroperitoneal lymphadenectomy not only is a staging procede but also is a therapeutic procedure.

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Donohue et al reviewed their 25-year experience with RPLND in 464 patients with clinical stage Adisease. Among the patients in whom pathologic stage II disease was detected at RPLND, 65% didnot relapse.[34] Therefore, a significant number of patients with low- stage II disease are cured byRPLND alone and do not require subsequent adjuvant chemotherapy or radiotherapy.Follow-up after RPLND is simple and efficient. Patients are followed with chest x-rays and tumormarker determinations. Also, relapse is rare, is usually in the chest when it does occur, and virtually100% of patients who suffer a recurrence are curable with chemotherapy.[35]Retroperitoneal lymphadenectomy eliminates the source of concern that most patients onsurveillance protocols inevitably feel; namely, that metastatic testicular cancer is being managedconservatively.Significant cost savings can be effected with RPLND due to the fact that follow-up does not includefrequent expensive imaging studies, as is the case with patients on surveillance protocols.Despite the obvious advantages of RPLND in clinical stage I disease, the procedure does havedrawbacks. The major disadvantage is the fact that 70% of clinical stage I patients do, in fact, havepathologic stage I disease, and therefore, are subjected to an unnecessary major surgical procedure,with its attendant morbidity. In centers of surgical expertise, RPLND carries a very low morbidity, andmortality approaches zero.[35,36] The average patient undergoing RPLND-I is under anesthesia forless than 3 hours, requires no blood transfusions, and is hospitalized for 5 to 7 days. Resumption oflimited employment and moderate activity can occur within 2 weeks, and a return to full activitynormally is possible within 4 to 6 weeks.[37] Fewer than 1% of patients develop the long-termmorbidity of small bowel obstruction due to adhesions.[38]Despite the fact that morbidity associated with RPLND-I is low, the need to identify patients withclinical stage I disease who are likely to harbor occult metastases is apparent and remains thesubject of ongoing studies. Albers et al[39] recently reported on the use of flow cytometry andsingle-cell cytophotometry in the prediction of metastases. They demonstrated that high proliferativeactivity, as measured by S- and G2M-phase analysis, was an important risk factor for occultmetastatic disease.Although surveillance may be a good approach for patients who do not relapse, it carries a distinctdisadvantage for those who relapse in the retroperitoneum and chest as late as 4 years or moreafter orchiectomy. The majority of this subset of patients will be subjected to three to four cycles ofchemotherapy with the possibility of resection of a residual mass following chemotherapy. Thus,both the short- and long-term morbidity of chemotherapy, needs to be weighed against the very lowmorbidity associated with RPLND-I. Furthermore, relapses carry a high mortality.In addition, rigid compliance to the follow-up protocol is necessary. Peters studied the impact onclinicians of entering patients into surveillance protocols.[40] He reported that a busy clinician maynot be able to adequately follow more than 25 patients on a surveillance protocol without the help ofa data manager.The completeness of RPLND is critical. Donohue et al[41] reported that none of their 464 patientswho underwent RPLND for clinical stage I disease relapsed in the retroperitoneum. Baniel et al[42]recently described a series of 35 patients initially diagnosed with low-stage NSGCT who presentedwith late (more than 2 years following initial management) relapse. A total of 31 patients wereinitially treated with RPLND, 19 of whom developed a retroperitoneal recurrence. Despite the factthat this subset had received chemotherapy following RPLND, 58% relapsed, implying that nodedissections were inadequate and that residual tumor may have transformed into a far more resistanttumor. In other words, inadequate RPLND for low-stage disease cannot be compensated for bysubsequent adjuvant chemotherapy.

Approach Used at Brigham and Women's Hospital

At the Brigham and Women's Hospital, we generally reserve RPLND-I for patients with high-riskclinical stage A nonseminoma. We define high-risk disease as: embryonal carcinoma more than 40%of tumor volume, any T-stage greater than T1, and any vascular or lymphatic invasion. All otherpatients are given the option of surveillance.We prefer the modified (template) technique, and generally use a mid-line transabdominal approach.Thus, a complete bilateral dissection is performed in the area most likely to contain positive lymphnodes, while the nerves controlling ejaculation are spared.

Summary

In summary, RPLND-I is generally performed for high-risk clinical stage I disease. This procedureaccurately stages the tumor and offers the patient the likelihood of a surgical cure. In addition,

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RPLND-I carries a very low risk of short- and long-term morbidity. Nevertheless, patient selectionneeds to be improved, and, in this regard, further research is required.

Management of Clinical Stage II Disease

The most appropriate form of therapy for patients with clinical stage II NSGCT is an area of ongoingdebate. This controversy centers on: (1) the role of adjuvant chemotherapy following RPLND and (2)surgery vs chemotherapy as initial treatment.Retroperitoneal lymph node involvement in patients with NSGCT, as detected by CT scan, isclassified as being less than 2 cm (stage IIA), between 2 and 5 cm (stage IIB), and more than 5 cm indiameter (stage IIC). There is general agreement that clinical stages IIC and III disease should bemanaged initially with chemotherapy, and that surgery should be reserved for residualretroperitoneal masses. However, the initial management of clinical stages IIA and IIB diseaseremains controversial.

Role of Adjuvant Chemotherapy

The 2-year disease-free survival rate for patients with pathologic stage II NSGCT following RPLND is60% to 80%, indicating a 20% to 40% incidence of recurrence, which is usually in the lungs. The roleof adjuvant chemotherapy following RPLND, vs an expectant approach with chemotherapyadministered at the time of recurrence, has been addressed by several authors.[43,44]A randomized multicenter study by Williams et al[45] reported a 48% relapse rate for patients withpositive nodes who were observed following RPLND-II. In contrast, the relapse rate in patients whoreceived 2 cycles of adjuvant chemotherapy following RPLND was 2%. This study included allpatients from stage N1 to N3 with positive nodes. There were no statistical differences in the relapserate among patients with various nodal stages.In contrast, Richie and Kantoff[43] reviewed 39 patients with pathologic stage II disease who werecarefully followed after RPLND-II. Relapses occurred in only 8% of patients, all of whom wererendered disease free with three to four cycles of chemotherapy. In other words, immediatepost-RPLND chemotherapy would have benefited only a relatively small number of patients. Thisstudy highlights the fact that results from institutions where RPLND is performed frequently may notparallel results from large cooperative trials, in which some centers contribute relatively smallnumbers of patients.In general, relapse rates for pathologic stage II disease resected by RPLND have ranged from 30% to70%.[43] As with clinical stage I disease, the question of overtreatment of clinical stage II diseasehas been raised. Thus, several reports have focused on the risk factors associated with a highlikelihood of recurrence following RPLND for clinical stage II disease. Javadpour and Young[46] notedincreased relapse rates in patients with more than five positive lymph nodes or any lymph nodemore than 2 cm in diameter and whose tumor displayed vascular invasion or was predominantlyembryonal in nature.Following RPLND-II, the decision to give two cycles of adjuvant chemotherapy depends largely on thetumor volume and number of positive lymph nodes, as well as on the histopathology of the primarytumor. Expectant management is appropriate in patients with fewer than six positive nodes (all ofwhich are less than 2 cm in diameter) and no positive margins.[39] For patients with more than sixpositive nodes or high-volume disease, two cycles of chemotherapy are given following RPLND; thisprotocol has achieved excellent cure rates.[47] For patients who develop a recurrence while beingtreated expectantly, chemotherapy is employed at that stage, once again with excellent remissionrates.


At Brigham and Women's Hospital,[46] most patients presenting with clinical stage IIA disease aretreated with RPLND-II. Patients with £ 3 cm of nodal involvement are offered RPLND, and forthose with more than 3 cm of nodal involvement, chemotherapy is generally recommended. Thisapproach often obviates double therapy. For patients with stage IIB disease and unfavorablehistology (teratomatous elements), RPLND is generally preferred, whereas for patients with pureembryonal stage IIB disease, chemotherapy is offered as first-line adjuvant therapy. In patients withpersistent tumor markers following radical orchiectomy and no evidence of retroperitonealinvolvement, chemotherapy is the initial treatment of choice. All patients with stage IIC disease arescheduled to receive initial chemotherapy.

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When suspicious lymph nodes are encountered at RPLND, we proceed with a complete bilateral nodedissection; for patients with palpable disease, the dissection also includes the suprahilar regions. Amid-line transabdominal approach is preferred for right-sided tumors, whereas a thoracoabdominalapproach is used for left-sided tumors. In patients with evidence of low-stage retroperitonealinvolvement and positive tumor markers following radical orchiectomy, we perform a bilateralcomplete RPLND.

Summary

Clinical stage II NSGCT can be managed in a variety of ways, depending on the tumor burden,histopathology, level of surgical expertise, and the patient's desires. The potential advantage ofRPLND is that it can eradicate disease in over 50% of patients with NSGCT. Patient compliance andmeticulous follow-up will usually ensure a successful outcome.

Management of Clinical Stage III Disease

Rationale for RPLND-III

In patients with advanced NSCGT, adjunctive surgery plays an important role in assessing responseto chemotherapy, resecting persistent germ cell tumor, and defining the need for further therapy.At institutions where RPLND-III is performed for residual disease only, three subsets ofhistopathology have been observed: necrosis/fibrosis (40%), adult teratoma only (40%), and resid-ual NSGCT (20%). Thus, approximately 60% of patients with evidence of a residual mass onpost-chemotherapy imaging studies have either viable cancer or teratoma.The criteria for RPLND-III are controversial, and there are no clear guidelines for its use. Thepresence of elevated tumor markers after chemotherapy, however, remains the only generallyaccepted contraindication to adjunctive surgery.[49] The management of patients whose tumormarkers normalize following chemotherapy ranges from observation for all patients, irrespective ofthe findings of the imaging studies, to surgery for all patients.[50,51]A significant number of patients with normal CT scans following chemotherapy, in fact, have viabletumor in the retroperitoneum. Richie reported viable germ cell tumor in 11 of 38 patients whounderwent adjunctive surgery following four cycles of chemotherapy.[52] However, the definition ofa "normal" CT scan differs from one institution to another. Definitions include: no visible mass, lymphnodes no larger than 1 cm, and lymph nodes less than 1.5 to 2 cm in greatest diameter.[43]RPLND-III is a very demanding procedure technically, and complication rates ranging from 6% to 8%have been reported. In view of this, several investigators have attempted to identify patients inwhom RPLND-III can be omitted. Among patients with no teratomatous elements detected in theprimary tumor and a ³ 90% decrease in the volume of retroperitoneal disease on sequential CTscans, Donohue and Rowland[53] found no teratoma or viable germ cell tumor elements in theresected specimen. On the other hand, Loehrer et al[54] reported that in 51 patients with teratomafound at post-chemotherapy resection, 28% of the primary specimens did not contain teratomatouselements.While there are statistical correlations between various factors, such as degree of tumor shrinkage,size of residual mass, prechemotherapy tumor markers, teratomatous elements in the primaryspecimen, and the histology of the resected specimen the risk of a false-negative prediction isapproximately 20%.[55] This false-negative rate has important implications due to the fact thatteratoma has the ability to grow rapidly and become unresectable. In addition, disease-free survivalfollowing RPLND-III for teratoma depends on the completeness of resection, and thus, earlyresections of teratoma are associated with the best possible chance of long-term disease-freesurvival.[56] Finally, there is a risk of malignant transformation of teratoma, ie, the development ofsarcomatous and nongerminal carcinomatous malignant elements.


At the Brigham and Women's Hospital, RPLND-III is performed in all patients with positive CT scans(visible mass) post-chemotherapy and in those whose primary tumor contained teratomatouselements. In patients with pure embryonal primary tumors who have a residual retroperitoneal massof Less than 2 cm following chemotherapy, an observation policy is adopted.We feel that the modified/nerve-sparing procedures are an unacceptable compromise in patientswith residual disease following chemotherapy, especially in those with frozen-section evidence of agerm cell tumor. Thus, we do not routinely employ these techniques as part of the RPLND-III.

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Patients exposed to bleomycin (Blenoxane) are carefully monitored during surgery. Also in suchpatients, the inspired concentration of oxygen is reduced, intraoperative and postoperative fluidreplacement is limited, and colloid solutions are used in place of crystalloid solutions.For patients with bulky disease, we prefer a left thoracoabdominal approach, through the bed of theeighth or ninth rib. However, for large retrocrural or posterior mediastinal disease, a higherthoracotomy or median sternotomy may be necessary. Patients with bulky teratoma may requireresection in stages; eg, chest followed by abdominal resection. Bulky retroperitoneal diseasemandates complete excision of all tissue, a procedure that is extremely challenging. Consequently,this procedure should be performed only by surgeons with the appropriate expertise.Residual disease composed of germ cell tumor elements is managed with another two cycles ofsalvage chemotherapy. If only teratoma or necrosis is detected, we require that patients receivechest and abdominal CT scans every 6 months, together with chest radiographs and serum tumormarkers every 2 months.

Summary

The surgical management of patients with evidence of residual disease after chemotherapy forNSGCT is both controversial and challenging. Management is based on post-chemotherapy imagingstudies, as well as on primary tumor histology. In view of the fact that these cases are extremelychallenging, they should be managed in centers where the necessary skills are available.

Conclusions

Tremendous advances have been made in the management of germ cell testis tumors during the20th century. With a multimodality approach, testicular cancer is curable in the vast majority ofcases. In addition, refinements in treatment modalities have minimized patient morbidity withoutcompromising disease-free survival rates.Retroperitoneal lymph node dissection not only provides accurate data for pathologic staging butalso is therapeutic in low-stage disease. Moreover, RPLND also plays an essential role in themanagement of high-stage disease, with respect to both directing further patient management andproviding long-term disease free survival following complete resection of residual teratoma. Precisesurgical technique is mandatory to ensure disease-free survival.Further improvements in the management of testicular cancer will come from better selection of low-and high-stage patients for adjuvant therapy. Genetic analysis of germ cell tumors may play a role inthis regard. References: 1. Schotterfeld D, Warshouer ME, Sherlock S, et al: The epidemiology of testicular cancer in youngadults. Am J Epidemiol 222:112, 1980.

2. Peterson GR, Lee JA: Secular trends of malignant tumors of the testes in white men. Cancer J Clin43:7, 1993.

3. Oliver RTD: Clues from natural history and results of treatment supporting the monoclonal originof germ cell tumors. Cancer Surv 9:333-368, 1990.

4. Hinman F: The operative treatment of tumors of the testicle. JAMA 63:2009, 1914.

5. Butt AP, Arkin A: Malignant diseases of the retained testicle. Surg Gynecol Obstet 19:419, 1914.

6. Rouviere H; Tobias MJ, trans: Anatomy of the Human Lymphatic System. Ann Arbor, Michigan,Edwards Bros, 1938.

7. Jamieson JK, Dobson JF: The lymphatic drainage of the testicle. Lancet 1:697, 1910.

8. Donohue JP, Zackery JM, Maynard BR, et al: Distribution of nodal metastases in nonseminomatoustestis cancer. J Urol 128:315-320, 1982.

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Links:[1] http://www.diagnosticimaging.com/review-article[2] http://www.diagnosticimaging.com/authors/graeme-s-steele-mbbch[3] http://www.diagnosticimaging.com/authors/jerome-p-richie-md

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