Clinical Outcomes in Clinical N0 Squamous Cell Carcinoma of the Penis According to Nodal Management: Early, Delayed or Selective (following Dynamic Sentinel Node Biopsy) Inguinal Lymph-Node Dissection.

PURPOSE: We evaluated the oncologic efficacy of early inguinal lymph-node dissection, observation or dynamic sentinel node biopsy followed by delayed or selective inguinal lymph-node dissection in cN0 patients with penile squamous cell carcinoma. MATERIALS AND METHODS: Between 1980 and 2017 (inclusive), 296 evaluable consecutive cN0 penile squamous cell carcinoma patients underwent early inguinal lymph-node dissection (16), observation (114) or dynamic sentinel node biopsy (166). Median followup was 50 months. Tumor stage, grade, lympho-vascular invasion and age were considered. Kaplan-Meier plots illustrated 5-year inguinal relapse-free and cancer specific survival rates. Multivariable Cox regression models tested the treatment effect. Analyses were repeated after inverse probability of treatment weighting adjustment. RESULTS: The 5-year inguinal relapse-free survival and cancer specific survival rates following early, observation and dynamic sentinel node biopsy inguinal lymph-node dissection were 100%, 87%, 89%, and 84%, 81%, 85%, respectively. The 5-year crude inguinal relapse-free survival and cancer specific survival rates were 90% and 93% in low-risk patients undergoing observation. Clavien grade 3 complications were 0.6 vs 12.5% in the dynamic sentinel node biopsy and early inguinal lymph-node dissection group, respectively. After inverse probability after treatment weighting adjustment, 5-year inguinal relapse and cancer specific survival were 90% vs 73% and 90% vs 77% following dynamic sentinel node biopsy and observation, respectively. At multivariable Cox regression model, patients undergoing dynamic sentinel node biopsy had significantly lower inguinal relapse (HR 0.4, 95% CI 0.2-0.85, p 0.02) and cancer specific mortality (HR 0.29, 95% CI 0.11-0.77; p=0.01) compared to those under observation. The low number of patients undergoing early inguinal lymph-node dissection made a reliable comparison with this group impractical. CONCLUSIONS: Selective inguinal lymph-node dissection following dynamic sentinel node biopsy significantly improved inguinal relapse and cancer specific mortality when compared with observation, providing evidence of efficacy of dynamic sentinel node biopsy in clinical stage N0 squamous cell carcinoma of the penis.

Laparoscopic Retroperitoneal Lymph Node Dissection for Clinical Stage I Nonseminomatous Germ Cell Tumors of the Testis: Safety and Efficacy Analyses at a High Volume Center.

PURPOSE: The prognosis of stage I nonseminomatous germ cell tumor of the testis is favorable. Early and late side effects of treatment may affect quality of life and survival. We determined the tolerability, safety and efficacy of laparoscopic retroperitoneal lymph node dissection in patients with stage I nonseminomatous germ cell tumor of the testis at a high volume center. MATERIALS AND METHODS: Unilateral laparoscopic retroperitoneal lymph node dissection was prospectively recorded in 225 patients from 2000 to 2014. Since 2007, patients have been treated at a multidisciplinary clinic and were proposed surgery as an alternative to surveillance or adjuvant chemotherapy. The indication for adjuvant chemotherapy changed during the study period. Descriptive statistics and regression analyses were used to evaluate the domains of safety and oncologic outcomes. RESULTS: A total of 221 patients were evaluable. Median operative time was 200 minutes. Conversion to open surgery was done in 20 cases (9%). A median of 14 nodes (IQR 11-20) was retrieved. Grade greater than 2 complications in 8 cases (3.6%) increased as the number of retrieved nodes increased. Antegrade ejaculation was maintained in 98.6% of patients. Nodal metastases were found in 29 patients (13%), of whom 7 underwent adjuvant chemotherapy. There were 14 recurrences (6.3%), including 8 of 192 (4.2%) associated with no nodal metastases and 6 of 22 (27.3%) associated with nodal metastases in patients not undergoing adjuvant chemotherapy. At regression analyses lymph node ratio was the only significant factor predictive of recurrence and of the administration of any chemotherapy (each p <0.001). Operative time, the number of retrieved nodes and conversions improved with time. CONCLUSIONS: In the context of a high volume center laparoscopic retroperitoneal lymph node dissection was safe and its oncologic efficacy was comparable to that of open surgery. Select patients with stage I nonseminomatous germ cell tumor could be offered laparoscopic retroperitoneal lymph node dissection as an alternative to other options.

A Combination of Cisplatin and 5-Fluorouracil With a Taxane in Patients Who Underwent Lymph Node Dissection for Nodal Metastases From Squamous Cell Carcinoma of the Penis: Treatment Outcome and Survival Analyses in Neoadjuvant and Adjuvant Settings.

BACKGROUND: The role of chemotherapy in nodal metastases from penile squamous cell carcinoma is not defined. We evaluated the efficacy of a combination of T-PF (a taxane, cisplatin, and 5-fluorouracil) in neoadjuvant and adjuvant settings. PATIENTS AND METHODS: Since June of 2004, T-PF was administered to stage N2 to 3 patients. With time, neoadjuvant chemotherapy administration prevailed with respect to use in the adjuvant setting. Primary end points were progression-free (PFS) and overall (OS) survival. Secondary objectives were tolerability and activity in the neoadjuvant setting. Nonparametric tests, Kaplan-Meier, and regression analyses were performed. RESULTS: As of October of 2012, 47 consecutive N2 to 3 M0 patients had undergone neoadjuvant (n = 28) or adjuvant (n = 19) T-PF: 18 patients (38.3%) remain disease-free after a median follow-up of 22 months (interquartile range, 17-42 months). The 2-year disease-free survivals were 36.8% (95% confidence interval [CI], 15.2-58.5) versus 7.1% (95% CI, 0-16.7) after adjuvant and neoadjuvant therapy, respectively. N3 metastases were associated with a poorer PFS, and bilateral metastases and mutated p53 were associated with a poorer OS. After neoadjuvant treatment, 43% clinical responses and 14% complete pathologic remissions were recorded, but responses were not associated with survival. Neutropenia (25.5%) was the most frequent Grade ≥ 2 toxicity. CONCLUSION: The T-PF regimen is well tolerated and compares with other regimens in terms of activity and efficacy in the neoadjuvant setting, and very long survivals have been recorded after adjuvant administration. The role of perioperative treatment in these patients remains controversial. Some caution in administering preemptive treatment in patients with resectable disease is needed.

Prognostic reclassification of patients with intermediate-risk metastatic germ cell tumors: Implications for clinical practice, trial design, and molecular interrogation.

OBJECTIVES: Approximately one-third of the metastatic germ cell tumors (GCT) in patients are classified as intermediate-risk metastatic GCT, and available guidelines recommend the same treatment of poor-risk cases. Yet the prognosis of these patients is heterogeneous, and consequently refining the intensity of treatment is warranted. We aimed to address the heterogeneity of this category by providing a proof of principle for reclassification attempt. PATIENTS AND METHODS: Data on consecutive patients with intermediate-risk metastatic GCT and who received treatment at Fondazione INT Milano in the time frame between February 1980 and March 2014 were collected. Cox regression analyses were done, evaluating potential prognostic factors for overall survival (OS, primary end point) to first-line therapy. Each factor was evaluated in a multivariable model. Recursive partitioning was performed to define prognostic risk groups. RESULTS: A total of 224 patients were suitable for the present analysis. Median age was 26 years (interquartile range: 22-31), 11 patients (4.9%) had a retroperitoneal primary tumor, 6 yielded seminomatous histology, 85 (37.9%) had lung metastases, and 58 (25.9%) had bulky (i.e.,≥ 10 cm) retroperitoneal lymph nodes. Patients received cisplatin, bleomycin, and etoposide (PEB, n = 199) or vinblastine (PVB, n = 23); however, 2 patients received other treatments. Median follow-up was 135 months (interquartile range: 81-223). Globally, 5-year progression-free survival and OS rates were 72.8% (95% CI: 67.1-79.0) and 86.2% (81.7-91.0), respectively. In the multivariable model for OS, elevated alfa fetoprotein (AFP) level was the only significant prognostic factor (hazard ratio = 1.48, 95% CI: 1.12-1.96). The 2 separate prognostic groups with differential OS outcomes were identified based on the cutoff level of 6,200 IU/ml. The 10-year OS rate was 55.6% (95% CI: 36.6-84.3), and it was 86.7% (95% CI: 82.0-91.7) for those with AFP levels more than (n = 19, 8.5%) and less than (n = 205, 91.5%) the cutoff, respectively. CONCLUSIONS: A small fraction of patients with highly elevated AFP levels have an OS approximating the poor prognostic category, whereas most of them are close to good-risk cases. This might have implications to select outlier patients for clinical trials and molecular characterization.

Clinical Outcomes of Metastatic Poor Prognosis Germ Cell Tumors: Current Perspective From a Referral Center.

BACKGROUND: Survival estimates with first-line treatment for patients with metastatic poor prognosis germ cell tumors (GCT) are still suboptimal in the literature. We conducted a retrospective study to evaluate the outcome of patients referred to our tertiary cancer center. PATIENTS AND METHODS: A retrospective analysis was conducted on patients who received at least first-line chemotherapy at our center. Distribution of clinical characteristics was evaluated in the periods < 1997, 1997 to 2001, 2001 to 2006, and 2007 to 2013. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariable and multivariable Cox models with prespecified clinical variables were undertaken for PFS and OS. All tests and confidence intervals were 2-sided and set at a P = .05 level of significance. RESULTS: Between 1982 and 2013, 168 patients were identified. The median age was 27 years (interquartile range [IQR], 22-34). The presence of liver, bone, or brain metastases trended to greater incidence from 1997 onward (27.5% < 1997 to 55.6% in 2007-2013; χ(2)P = .054). Median follow-up was 102 (IQR, 63-166) months. Global 5-year PFS was 48.5% (95% confidence interval [CI], 41.5-56.8) and OS was 63.2% (95% CI, 56.0-71.2). In multivariable analysis, treatment period was not significantly associated with either PFS (overall P = .229) or OS (overall P = .216). CONCLUSION: In this single-center series of consecutive poor prognosis GCT we could observe greater PFS and OS than the historical estimates. This observation was independent from the period of treatment. Based on the present results, studies focused on improving the outcome in the sole poor-risk cohort should be discouraged. Results were biased by their retrospective quality.

Clinical outcome in testicular sex cord stromal tumors: testis sparing vs. radical orchiectomy and management of advanced disease.

OBJECTIVE: To assess the clinical outcome of testicular sex cord stromal tumors (TSCST) according to management and stage. PATIENTS AND METHODS: Clinical and pathologic features, stage, and treatment of patients with TSCST were retrieved from our database. The Kaplan-Meier method estimated the relapse-free survival and cancer-specific survival. RESULTS: We identified 67 patients between December 1982 and January 2013: 55 patients (82.1%) had a Leydig cell tumor and 11 patients (16.4%) had a Sertoli cell tumor. Four patients (5.9%) presented with gynecomastia. Forty-eight patients (71.6%) had no pathologic risk factor, and patients 3 had ≥3 risk factors. Testis-sparing surgery was performed in 31 patients (46.3%) and orchiectomy in 36 patients (53.7%). The median tumor diameter was 0.7 cm (interquartile range, 0.6-1.3) and 1.5 cm (interquartile range, 0.9-2.6) in the 2 groups, respectively (P, .007 at Mann-Whitney rank-sum test). The 5-year relapse-free survival was 89.4% (95% confidence interval, 75.9%-95.5%) and cancer-specific survival was 90.3% (95% confidence interval, 72.7%-96.7%), respectively. Metastases were documented in 8 patients (11.9%), 5 relapsing after a median follow-up of 37.4 months. All 3 patients with ≥3 risk factors had metastatic disease. Four of 5 patients with retroperitoneal metastases only were cured by retroperitoneal lymph node dissection (3 patients at presentation and 1 during follow-up); 4 patients undergoing chemotherapy progressed and ultimately died of disease. CONCLUSION: Most of the patients with TSCST had a favorable prognosis. Testis-sparing surgery may be feasible and effective in case of small tumors. Few patients had metastatic spread, but only those with nodal metastases may benefit from an early retroperitoneal lymph node dissection. Risk factors associate with disease behavior, but indications to prophylactic intervention remain controversial.

Relationship between lymph node ratio and cancer-specific survival in a contemporary series of patients with penile cancer and lymph node metastases.

OBJECTIVE: To evaluate the association between lymph node ratio (LNR) and cancer-specific survival (CSS) in a population of patients with penile cancer and lymph node metastases (LNM). PATIENTS AND METHODS: We evaluated 81 patients with pathologically determined LNM who were surgically treated at our institution between 2000 and 2012. We considered LNR both as a continuously coded and as a categorically coded variable. The minimum-P-value approach was used to determine the most significant LNR threshold. The Kaplan-Meier method was used to determine CSS rates, and univariable and multivariable Cox regression models were fitted to test the predictors of CSS. RESULTS: The median (interquartile range [IQR]) numbers of positive and removed lymph nodes were 2 (1-4) and 22 (13-30), respectively. The median (IQR) LNR was 10.3 (6.3-16.6)% and the most significant LNR threshold was 22%. The median (IQR) follow-up was 26 (16-62) months. Overall, the 5-year CSS rate was 50.5%. After stratification according to LNR, 5-year CSS rates were 65.2% vs 9.6% in patients with LNR < 22% vs LNR ≥ 22%, respectively (P < 0.001). In multivariable Cox regression models, after adjusting for several established prognostic factors, LNR was as independent predictor of CSS (P≤0.012). Finally, LNR significantly improved the accuracy of multivariable Cox regression models by 4.9-10.5%. CONCLUSIONS: Although further investigations are needed to evaluate the relationship between tumour burden and treatment intensity, LNR may represent a powerful predictor of CSS in patients with penile cancer and pathologically determined LNM.

Long-term efficacy and safety outcomes of modified (simplified) MVAC (methotrexate/vinblastine/doxorubicin/cisplatin) as frontline therapy for unresectable or metastatic urothelial cancer.

BACKGROUND: The classic MVAC (methotrexate/vinblastine/doxorubicin/cisplatin) regimen was the first recognized option for untreated patients with locally advanced or metastatic urothelial cancer (UC). Modifying MVAC by reducing side effects may have the potential to improve efficacy. PATIENTS AND METHODS: Changes to classic MVAC were provided at the authors' institution: (1) deletion of day 22 and administration of 25 mg/m(2) cisplatin on days 2 to 5 (modified [m]MVAC); (2) deletion of day 22 only (simplified [s]MVAC1); and (3) deletion of days 15 and 22 in a 3-week schedule (sMVAC2). A total of 4 to 6 cycles were provided. Multivariate analysis was undertaken for recognized clinical variables. RESULTS: For the period from September 1986 to May 2012, 157 patients were identified (25 with mMVAC, 72 with sMVAC1, and 60 with sMVAC2). Overall, 43.9% had a Memorial Sloan-Kettering Cancer Center score of 1 or 2, with differences across series (P = .002). Altogether, 65.8% attained a complete (19.1%) or partial response (46.7%), and 24.3% a stable disease, with no difference across regimens. After a median follow-up of 87 months (interquartile range, 37-161), median progression-free survival was 10.2 months (95% CI, 8.4-10.8), and median overall survival (OS) was 19.5 months (95% CI, 16.3-24.1). Responses were mainly seen in nodal metastases or soft tissue relapse (odds ratio, 2.48; 95% CI, 1.12-5.54). Only visceral (hazard ratio [HR], 2.42; 95% CI, 1.37-4.30) and nodal metastases/local relapse (HR, 1.70; 95% CI, 1.07-2.69) were independently associated with OS. Grade 3 or 4 toxicities were similar across regimens and were 36% neutropenia, 14% thrombocytopenia, 12% anemia, 10% mucositis, and 4% renal toxicity. Two treatment-related deaths occurred. CONCLUSION: Simplifying MVAC may result in improved efficacy and reduced toxicity. The combined results of the original and modified MVAC regimens encourage a reappraisal of the frontline management of advanced UC.

The relationship between characteristics of inguinal lymph nodes and pelvic lymph node involvement in penile squamous cell carcinoma: a single institution experience.

PURPOSE: We determined predictors of pelvic lymph node metastases in patients with penile cancer. MATERIALS AND METHODS: We retrieved a total of 188 node positive inguinal groins from 142 patients treated for penile cancer. Logistic regression models were fitted to test for predictors of pelvic lymph node metastases. The minimum p value method was used to determine the most significant cutoff values of each predictor. RESULTS: Pelvic lymph node metastases were observed in 45 cases (31.7%). The 5-year cancer specific survival rate was 71.0% vs 33.2% in patients with inguinal vs pelvic lymph node metastases. The most significant cutoff values were 3 inguinal lymph node metastases and a metastasis diameter of 30 mm. According to univariable logistic regression models the number of inguinal metastases (OR 1.92, p <0.001), the diameter of the metastases (OR 1.03, p = 0.001) and extranodal extension (OR 8.01, p <0.001) were significant predictors of pelvic lymph node metastases. These variables were also independent predictors of metastases in multivariable logistic regression models (p ≤ 0.012). Patients with 3 or more inguinal lymph node metastases and those with a metastasis diameter of 30 mm or greater were at 4.77 and 2.53-fold higher risk, respectively, of harboring pelvic lymph node metastases (p ≤ 0.006). The proportion of metastases increased significantly from 0% in cases with no risk factors to 57.1% when all 3 risk factors were observed (p <0.001). CONCLUSIONS: The number and diameter of inguinal lymph node metastases as well as extranodal extension are significantly associated with pelvic lymph node metastases. These variables should be considered to determine the need for pelvic lymph node dissection. Patients with no risk factors may be spared this dissection.

Long-term outcome of salvage high-dose chemotherapy in patients with germ cell tumor with poor prognostic features.

OBJECTIVE: High-dose chemotherapy (HDCT) represents an option as salvage treatment for patients with resistant/refractory germ cell tumor (GCT). The objective of this retrospective analysis was to evaluate the long-term results of a single-center experience with salvage HDCT for GCT patients, and to validate the prognostic model proposed by Einhorn and colleagues [9]. MATERIALS AND METHODS: Between 1986 and 2003, 100 GCT patients received salvage HDCT consisting of high-doses of carboplatin, etoposide ± cyclophosphamide, or ifosfamide. Twenty-four patients underwent a second HDCT cycle, and in 1 case, a third cycle was given with a median interval time of 6 weeks (range, 5-10). RESULTS: With a median follow-up of 8 years (range, 3-17); 6 of 32 (19%) patients with resistant GCT and 1 of 19 (5%) patients with cisplatin-refractory disease have been continuously disease-free, while none of the 16 patients with absolutely cisplatin-refractory GCT were alive at 1 year from HDCT treatment. In the PBPC era, HDCT appeared to be inapplicable in 32% of patients, mainly due to progressive disease during the induction/mobilizing phase. The prognostic model by Einhorn et al. for tandem HDCT did categorize our patients treated with a single HDCT cycle or low-dose intensity regimens in a very similar manner, but with inferior overall results. CONCLUSIONS: Long-term results with a single HDCT cycle or a low dose-intensity multicycle HDCT regimen remained poor in patients with adverse prognostic features. The tandem HDCT regimen represents a major option for refractory GCTs and relapsed tumors in third-line or later therapy, while a single course of HDCT should be abandoned for these patients.

Retroperitoneal lymph node dissection with no adjuvant chemotherapy in clinical stage I nonseminomatous germ cell tumours: long-term outcome and analysis of risk factors of recurrence.

BACKGROUND: The best management for patients with clinical stage I (CS1) nonseminomatous germ cell tumours (NSGCT) is still under debate. OBJECTIVE: We evaluated the long-term oncologic outcome of retroperitoneal lymph node dissection (RPLND) in patients with CS1 NSGCTs and reevaluated the traditional predictors of recurrence in a set of patients not undergoing adjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS: Between 1985 and 1995, 322 consecutive CS1 NSGCT patients underwent primary RPLND not followed by adjuvant chemotherapy in a single referral centre. Patients were followed until relapse for a median time of 17 yr. MEASUREMENTS: We estimated the crude cumulative incidence of any recurrence. Categories pN and pT, vascular invasion (VI), percentage of embryonal carcinoma, and presence of teratoma were evaluated as 2-yr recurrence predictors of event in a binary logistic model. RESULTS AND LIMITATIONS: Fifty patients had a recurrence (46 in ≤ 2 yr and only 4 [1.2%] in > 2 yr). The 10-yr recurrence incidence was 15.2%. Significant predictors of recurrence at multivariable analysis were pN+, pT > 1, and the presence of VI. However, the discriminative ability of the model was modest (Harrell C = 0.74); only 9% and 3% of patients had a predicted recurrence probability > 30% and > 50%, respectively. CONCLUSIONS: RPLND alone could prevent recurrence in 85% of patients and minimise late relapses to 1.2%. Most patients could avoid the immediate and late toxicity of chemotherapy. Prognostic parameters combined into the multivariable model appeared of limited use in identifying a subset of patients at high risk of recurrence.

EAU penile cancer guidelines 2009.

CONTEXT: Squamous cell carcinoma (SCC) of the penis is a relatively rare but ominous disease. OBJECTIVE: To present a condensed version of the updated 2009 European Association of Urology (EAU) guidelines on penile SCC. EVIDENCE ACQUISITION: We performed a literature search of new data available up to December 2009. No randomized study was found; consequently, level of evidence (LE) and grade of recommendations (GR) are low. EVIDENCE SYNTHESIS: More insight was gained into the etiology of SCC of the penis, together with improved staging and treatment: Human papillomavirus 16 plays an etiologic role in approximately 40-50% of cases. Similarities in etiology with SCC of the head and neck, the female genitalia, and the anal canal have been found. Improved diagnostics allowed earlier diagnosis, leading to more conservative treatments. Adjuvant and neoadjuvant chemotherapy showed promising results in patients with advanced or recurrent disease. Centralization of the disease contributed to standardization and rapid diffusion of new treatments with improved results and increased organ preservation. CONCLUSIONS: Improvements in the management of SCC of the penis are reflected in changes in the guidelines, but the rarity of the disease precluded randomized studies, leading to low level of evidence and grade of recommendation.

Organ-sparing surgery for adult testicular tumours: a systematic review of the literature.

CONTEXT: According to current guidelines, radical orchidectomy is the standard treatment for testis tumours of malignant and unknown origin. Testis-sparing surgery (TSS) has recently been proposed as an alternative option in selected cases. OBJECTIVE: Our aim was to analyse the cumulative evidence for TSS in the treatment of adult malignant tumours of different histology, including notes on operative technique, indications, complications, and oncologic and functional outcome. EVIDENCE ACQUISITION: A systematic literature search of the Medline/PubMed database for full-length papers reporting on TSS for adult malignant tumours was performed up to September 2009. Bibliographies of retrieved articles and review articles were also examined. Only those articles with complete data on operative technique, complications, and oncologic or functional outcome were selected. Furthermore, published abstracts at major urologic meetings in the last decade (1999-2009) and guidelines on testis cancer from major oncologic and urologic medical associations were searched and evaluated. EVIDENCE SYNTHESIS: No randomised controlled trials have compared TSS and radical orchidectomy; only retrospective outcome studies and case reports on TSS are available. In patients with small malignant germ cell tumours arising in both or in solitary testes, TSS coupled with local adjuvant radiotherapy ensures good oncologic control and is associated with a preserved endocrine function in most cases. In patients with small Leydig cell tumours, TSS can also be performed with elective indications (healthy contralateral testes), provided that pathology fails to reveal aggressive features. Finally, TSS is an option for patients with small ultrasound-detected, nonpalpable tumours even with elective indications because the incidence of benign definitive histology is high at approximately 80%. The overall complication rate is low (<6%). Data on exocrine and endocrine gonadal function, male body image, and health-related quality of life after TSS are still immature. CONCLUSIONS: TSS can be safely adopted for the treatment of carefully selected cases of tumours of different histology. Prospective multicentre studies are warranted to further qualify TSS as a treatment option to be recommended as an alternative to radical orchidectomy and to explore the perceived functional advantages of testis preservation.

pT1 penile squamous cell carcinoma: a clinicopathologic study of 56 cases treated by CO2 laser therapy.

OBJECTIVE: To evaluate the pathologic characteristics that are associated with outcomes in pT1 penile squamous cell carcinoma (SCC) treated with laser excision. STUDY DESIGN: Peniscopic magnification and 5% acetic acid application were performed prior to CO2 laser excision. Specimens were reviewed to reassess stage, grade, invasion depth, carcinoma in situ, margins, tumor extension, lymphovascular invasion and human papillomavirus infection. Association between local recurrence (LR) and prognostic factors was established with Fisher exact test, chi2 test for categorical variables and Wilcoxon rank sum test for continuous variables. RESULTS: After a median follow-up of 66 months, 53 of 56 patients were alive and disease free; 3 died of unrelated and intercurrent diseases. Thirteen had an LR, with 4 experiencing multiple recurrences and 1 needing a partial amputation. Two patients had inguinal nodal metastasis in 1 node. LR had a positive correlation with positive surgical margins and depth of invasion and a negative correlation with tumor extension. CONCLUSION: Histopathologic parameters such as margin status, depth of invasion and tumor extension are predictors of LR in T1 penile SCC treated by CO2 laser excision. A logistic model could estimate each patient's risk of LR.

Lymphadenectomy in the surgical management of penile cancer.

CONTEXT: Uncertainty remains about the extent and indications for inguinal lymphadenectomy in penile cancer, a procedure known for relatively high morbidity. Several attempts have been made to develop strategies which can improve the diagnostic quality and reduce the morbidity of the management of inguinal lymph nodes in penile cancer. OBJECTIVE: To analyse the existing published data on the surgical management of inguinal nodes in penile cancer regarding morbidity and survival. EVIDENCE ACQUISITION: A Medline search was performed of the English-language literature (1966-September 2008) using the MeSH terms penile carcinoma, lymph node dissection, lymphadenectomy, and complications. EVIDENCE SYNTHESIS: Lymph node metastases are frequent in penile cancer, even in early pT1G2 stages. Since the results of systemic treatment of advanced penile cancer are disappointing, complete dissection of all involved lymph nodes is highly recommended. The extent of lymph node dissection should be adapted to clinical stage, as this corresponds to metastatic spread. For low-risk patients (pTis, pTa, and pT1G1) without palpable lymph nodes and with good compliance, a surveillance strategy may be chosen. For all other patients without palpable lymph nodes (including intermediate risk pT1G2 disease), a modified bilateral lymphadenectomy is recommended. An alternative to this is a dynamic sentinel lymph node biopsy in specialised centres. All patients with histologically proven lymph node metastases should undergo radical inguinal lymphadenectomy. Pelvic lymph node dissection should be done in all patients with more than two metastatic inguinal lymph nodes. In case of fixed inguinal lymph nodes, neoadjuvant chemotherapy is recommended, followed by node resection. CONCLUSIONS: Lymphadenectomy is an integral part of the management of penile cancer, since early dissection of involved lymph nodes improves survival.

Long-term results of a combination of paclitaxel, cisplatin and gemcitabine for salvage therapy in male germ-cell tumours.

OBJECTIVE: To retrospectively review the long-term activity, efficacy and toxicity of the combination of paclitaxel, cisplatin and gemcitabine (TPG) as third- or further-line chemotherapy in patients with germ-cell tumours (GCTs) who are not cured after at least two courses of standard-dose chemotherapy, high-dose chemotherapy or both. PATIENTS AND METHODS: We evaluated 22 consecutive men treated between April 1999 and December 2000. Half of them were classified as absolutely refractory to cisplatin and a further two as refractory. The median (range) number of previous courses of chemotherapy was 8 (5-11). Treatment consisted of paclitaxel 80 mg/m(2), cisplatin 50 mg/m(2) and gemcitabine 800 mg/m(2) on days 1 and 8, every 3 weeks for four courses, followed by surgery of actual residual resectable masses. RESULTS: The follow-up was updated at August 2007. There were no deaths from toxicity and only one patient needed suspension of therapy for toxicity. There was both grade 3-4 thrombocytopenia and neutropenia in 15 patients (68%), and anaemia in nine (41%). There were partial remissions in eight (36%) patients. Six (27%) patients were rendered disease-free with surgical removal of a residual mass after chemotherapy (two still containing viable cancer). Four (18%) patients are long-term survivors at more than 80, 81, 94 and 99 months. The median (range) overall survival of the whole series was 13.5 (1->99) months. CONCLUSION: This combination had a toxicity profile that was acceptable and comparable with other third-line regimens. There were eight (36%) major responses. After a 6-year minimum follow-up, four (18%) patients were long-term disease-free survivors.

Taxanes in combination with cisplatin and fluorouracil for advanced penile cancer: preliminary results.

BACKGROUND: Chemotherapy is emerging in the management of advanced penile cancer. OBJECTIVE: To evaluate the therapeutic activity of taxanes (T) in combination with cisplatin-fluorouracil (PF) for salvage of primarily unresectable or relapsed nodal metastases from squamous cell carcinoma (SCC) of the penis. DESIGN, SETTING, AND PARTICIPANTS: Six consecutive patients were treated at Istituto Nazionale Tumori (INT), Milano, with neoadjuvant paclitaxel, cisplatin, and 5-fluorouracil (TPF) for unresectable (two cases) or recurrent nodal metastases (four cases) from SCC of the penis from 2004 to 2006. Informed consent was given by all patients. INTERVENTION: Four courses of neoadjuvant TPF were to be given before salvage surgery. MEASUREMENTS: Patients underwent computed tomography (CT) scans before starting chemotherapy, after two courses, and at the end of chemotherapy. Lymph node dissection was to be performed in responsive patients. RESULTS AND LIMITATIONS: Two patients received more than four courses: Both had pathologically documented complete remission, and they are alive and disease free >2 yr after chemotherapy. The other four patients received only two courses. The first patient had subjective intolerance to TPF: He underwent early postchemotherapy radical lymph node dissection, which documented >90% tumour necrosis: He is alive and disease free 46 mo after starting chemotherapy. Of the other three patients, one was not responsive, changed therapy, and died within 4 mo. The other two had a clinical complete remission after the first two courses. Both refused to complete chemotherapy, and they relapsed after 10 and 4 mo. Limitations are the small number of patients and protocol violation in three cases. CONCLUSIONS: TPF chemotherapy for unresectable or recurrent nodal metastases from SCC of the penis is promising, and the standard four courses of therapy are to be completed in responding patients. A larger series is necessary to confirm preliminary results.