Lymph Node Metastases and Prognosis in Penile Cancer

Lymph node status is a key prognostic factor in penile squamous cell carcinoma. Recently, growing evidence indicates a multimodality approach consisting of neoadjuvant chemotherapy followed by consolidation surgery improves the outcome of locally advanced penile cancer. Thus, accurate estimation of survival probability in node-positive penile cancer is critical for treatment decision making, counseling of patients and follow-up scheduling. This article reviewed evolving developments in assessing the risk for cancer progression based on lymph node related variables, such as the number of metastatic lymph nodes, bilateral lymph node metastases, the ratio of positive lymph nodes, extracapsular extension of metastatic lymph nodes, pelvic lymph node metastases, metastatic deposit in sentinel lymph nodes and N stage in TNM classification. Controversial issues surrounding the prognostic value of these nodal related predictors were also discussed.

Updates in the use of radiotherapy in the management of primary and locally-advanced penile cancer

Objective:Penile cancer is a rare malignancy in most developed countries,but may represent a significant oncologic challenge in certain African,Asian,and South American regions.Various treatment approaches have been described in penile cancer,including radio-therapy.This review aimed to provide a synopsis of radiotherapy use in penile cancer management and the associated toxicities.In addition,we aimed to discuss palliative radiation for metastases to the penis and provide a brief overview of how tumor biology may assist with treatment decision-making.Methods:Peer-reviewed manuscripts related to the treatment of penile cancer with radio-therapy were evaluated by a PubMed search(1960-2021)in order to assess its role in the definitive and adjuvant settings.Selected manuscripts were also evaluated for descriptions of radiation-related toxicity.Results:Though surgical resection of the primary is an excellent option for tumor control,select patients may be treated with organ-sparing radiotherapy by either external beam radiation or brachytherapy.Data from randomized controlled trials comparing radiotherapy and surgery are lacking,and thus management is frequently determined by institutional practice patterns and available expertise.Similarly,this lack of clinical trial data leads to divergence in opinion regarding lymph node management.This is further complicated in that many cited studies evaluating lymph node radiotherapy used non-modern radiotherapy delivery techniques.Groin toxicity from either surgery or radiotherapy remains a challenging problem and further risk assessment is needed to guide intensification with multi-modal therapy.Intrinsic differences in tumor biology,based on human papillomavirus infection,may help aid future prognostic and predictive models in patient risk stratification or treatment approach.Conclusion:Penile cancer is a rare disease with limited clinical trial data driving the majority of treatment decisions.As a result,the goal of management is to effectively treat the disease while balancing the importance of quality of life through integrated multidisciplinary discussions.More international collaborations and interrogations of penile cancer biology are needed to better understand this disease and improve patient outcomes.

Penile cancer:Updates in systemic therapy

Penile cancer is a rare genitourinary malignancy with a greater incidence in parts of Asia,South America,and Africa.Outcomes are very poor in patients with advanced disease and in those who do not respond to frstine mutimodal therapy.Among systemic therapy options,platinum-based chemotherapy is used in the frst line;however,approximately half of patients do not benefit.Response rates to systeric therapy as subsequent line treatment are historically dismal.There is also a paucity of prognostic and predictive tools within the context of penile cancer.As such,there remains an urgent need to expand systemic treatment options for patients with advanced penile cancer.The purpose of this review is to summarize the existing evidence for standard-of-care lines of systemic treatment,examine the potential of novel lines of systemic therapy,and provide an update as to the status of these new therapies within the context of penile cancer.

Sexual outcomes after partial penectomy for penile cancer： results from a multi-institutional study

Penile cancer is an uncommon malignancy. Surgical treatment is inevitably mutilating. Considering the strong impact on patients＇ sexual life we want to evaluate sexual function and satisfaction after partial penectomy. The patients in this study （n = 25） represented all those who attended our institutions and were diagnosed and treated for penile cancer from October 2011 to November 2013. All patients underwent partial penectomy and followed-up （mean： 14 months; range： 12-25）. Sexual presurgical baseline was estimated using the International Index of Erectile Dysfunction 15 （IIEF-15）. Sexual outcomes of each patient were estimated considering four standardized and validated questionnaires. We analyzed the means and ranges of IIEF-15 including erectile function （IIEF-1-5 and -15）, orgasmic function （IIEF-9 and -10）, sexual desire （IIEF-11 and -12）, intercourse satisfaction （IIEF-6-8）, and overall satisfaction （IIEF-13 and -14）. Then, we also used Quality of Erection Questionnaire （QEQ）, Erectile Dysfunction Inventory of Treatment Satisfaction （EDITS） and Self-Esteem and Relationship （SEAR） to evaluate the sexual function and satisfaction of our patients. The final results showed that penile cancer leads to several sexual and psychosexual dysfunctions. Nevertheless, patients who undergo partial penectomy for penile cancer can maintain the sexual outcomes at levels slightly lower to those that existed in the period before surgery.

Neoadjuvant chemotherapy for patients with locally advanced penile cancer:an updated evidence

Neoadjuvant chemotherapy(NAC)has shown promising results in patients with locally advanced penile cancer.However,no consensus exists on its applications for locally advanced penile cancer.Thus,it is unclear which kind of chemotherapy regimen is the best choice.Consequently,a systematic search of PubMed,Web of Science,and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer.The Newcastle–Ottawa Scale was used to assess the risk of bias in each study.This study synthesized 14 published studies.The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response.In addition,the objective response rates(ORRs)and pathological complete response(pCR)rates were 0.57 and 0.11,respectively.The incidence of grade≥3 toxicity was 0.36.Subgroup analysis found that the ORR and pCR of the taxane–platinum(TP)regimen group performed better than those of the nontaxane–platinum(NTP)regimen group(0.57 vs 0.54 and 0.14 vs 0.07,respectively).Moreover,the TP regimen group had more frequent toxicity than the NTP regimen group(0.41 vs 0.26).However,further studies were warranted to confirm the findings.

Advances in penile-sparing surgical approaches

Objective:Penile cancer(PeCa)is a rare disease with a global incidence of 36068 new cases in 2020.This accounts for 0.4%of all male malignancies.The surgical management of PeCa depends on the location of the tumour and depth of invasion.Here,we review the oncological and functional outcomes of penile-preserving surgery(PPS).Methods:A PubMed search until July 2021 on PPS for PeCa was conducted;a narrative review on different penile-sparing approaches and outcomes was performed.Results:PPS is now the standard of care in specialist centres for distal tumours not involving the corpus cavernosa.Laser therapy,glans resurfacing,and wide local excision are options for superficial lesions,whilst glansectomy is required for lesions invading into the corpus spongiosum.Conclusion:PPS aims to preserve urinary and sexual function without compromising oncological outcomes.

阴茎再造术最新进展

Penile reconstruction still represents a formidable challenge for the urologist. In this review, the most recent advances in penile reconstruction after trauma, excision of benign and malignant disease and in patients with micropenis, aphallia or female to male gender dysphoria are reported.

Up-regulation of indoleamine 2,3-dioxygenase 1(IDO1)expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan (Trp)catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penilesquamous cell carcinoma (PSCC) and explored their clinical significance.Methods: IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn)were examined in 114 PSCC patients by immunohistonchemistry and solid-phaseextraction-liquid chromatography-tandem mass spectrometry. The survival was analyzed using Kaplan-Meier method and the log-rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were definedby principal component analysis. The correlativity was assessed by Pearson’s correlation analysis.Results: The expression level of IDO1 in PSCC cells was positively correlatedwith serum Kyn concentration and Kyn/Trp radio (KTR;both P < 0.001) but negatively correlated with serum Trp concentration (P = 0.001). Additionally, IDO1 upregulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both P < 0.001) and high pathologic grade (P = 0.008and 0.032, respectively). High expression level of IDO1 in cancer cells and serumKTR were associated with short disease-specific survival (both P < 0.001). However, besides N stage (hazard radio [HR], 6.926;95% confidence interval [CI],2.458-19.068;P < 0.001) and pathologic grade (HR, 2.194;95% CI, 1.021-4.529;P = 0.038), only serum KTR (HR, 2.780;95% CI, 1.066-7.215;P = 0.036) was anindependent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon-𝛾 (IFN𝛾, P < 0.001) and immunosuppressivemarkers (programmed cell death protein 1, cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 and 2;all P < 0.05), and the infiltration ofimmune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumorassociated macrophages, and myeloid-derived suppressor cells;all P < 0.001) inPSCC tissues. Furthermore, the expression of IDO1 was induced by IFN𝛾 in a dosedependent manner in PSCC cells.Conclusions: IFN𝛾-induced IDO1 plays a crucial role in immunoediting andimmunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1catabolic activity, can be utilized as an independent prognostic factor for PSCC.